NeoplasmsPhase 1NCT00141297
A Study Of Oral Palbociclib (PD-0332991), A Cyclin-Dependent Kinase Inhibitor, In Patients With Advanced Cancer
A Phase 1 study testing PD-0332991 in people with Neoplasms and Lymphoma, Non-Hodgkin, run by Pfizer at 4 sites in United States.
Trial summary
PD-0332991 may work in cancer by stopping cancer cells from multiplying. PD-0332991 is in a new class of drugs called cyclin-dependent kinase (CDK inhibitors). This research study is the first time that PD-0332991 will be given to people. PD-0332991 is taken by mouth daily. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms, Lymphoma, Non-Hodgkin
- What is being tested?
- PD-0332991
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 4 sitesUnited States
- Study dates
- Sep 2004to Dec 2014
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Advanced solid tumors (excluding SCLC and retinoblastoma) or follicular of diffuse large cell non-Hodgkin's lymphoma, histologically or cytologically proven at diagnosis which is refractory to or intolerant of established therapy know to provide clinical benefit for their condition; tumors must express Rb
- Adequate blood cell counts, kidney function and liver function and and ECOG score of 0, 1, or 2.
- Patients may have to have tumor biopsy before and after treatment.
Who cannot join
- Prior stem cell or bone marrow transplant
- Uncontrolled infection, unstable or sever intercurrent medical condition, or current drug or alcohol abuse
- Active or unstable cardiac disease or history of heart attack within 6 months
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Karmanos Cancer Institute
Detroit, Michigan, 48201
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Abramson Cancer Center Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Pharmacy/PCAM/West Pavillion
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Phase I Clinical, Pharmacokinetic, And Pharmacodynamic Evaluation Of 2 Schedules Of Oral PD 0332991, A Cyclin-Dependent Kinase Inhibitor, In Patients With Advanced Cancer
PD-0332991 may work in cancer by stopping cancer cells from multiplying. PD-0332991 is in a new class of drugs called cyclin-dependent kinase (CDK inhibitors). This research study is the first time that PD-0332991 will be given to people. PD-0332991 is taken by mouth daily.
- Conditions
- Neoplasms, Lymphoma, Non-Hodgkin
- Being tested
- PD-0332991
- Keywords
- Advanced cancer
- Medical subject headings
- Neoplasms, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PD-0332991Drug
Dose ranging study - evaluating two oral schedule: (1) 3/1 Schedule - PD-0332991 administered days 1-21 of a 28-day schedule, doses ranging from 25 to 150 mg once daily; (2) 2/1 Schedule - PD-0332991 administered days 1-14 of a 21-days schedule, doses ranging from 100 to 225 mg once daily
| Study group | Role | What they receive |
|---|---|---|
| PD-0332991 | Experimental | Not described Receives: Drug: PD-0332991 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose-Limiting Toxicities (DLT)
DLT: an adverse event occurring after initiation of PD 0332991 that met any following criteria: 1) Grade 4 hematologic toxicity (platelets less than [<] 25000 per microliter (mcL), absolute neutrophil count [ANC] <500/mcL, hemoglobin [Hb] <6.5 gram per deciliter [g/dL]; 2) ANC <1000/mcL associated with documented infection or fever greater than or equal to (>=) 38.5 degrees Celsius; 3) >=Grade 3 non-hematologic treatment-related toxicity. In an asymptomatic participant, Grade 3 corrected QT (QTc) prolongation (>500 millisecond) (only if persisted with repeat testing and after correction of reversible causes [electrolyte abnormalities or hypoxia]); and 4) Inability to receive next dose of PD 0332991 within 1 week (+/-1 day) of last dose due to lack of hematologic recovery (platelets <50000/mcL, ANC <1000/mcL, and Hb <8.0 g/dL) or due to prolonged non-hematologic toxicities of >=Grade 3 severity. Occurrence of a DLT necessitated immediate interruption of scheduled study treatment.
Measured: Baseline up to 28 days
Maximum Administered Dose (MAD)
Three new evaluable participants were to be assessed at each new dose level. The minimum time that these participants were to be followed after starting treatment was 1 cycle (28 or 21 days) before a new dose level could be opened. If none of these 3 participants experienced a DLT, the next higher dose level was to be opened on that schedule. If 1 participant developed a DLT, 3 more evaluable participants were to be enrolled at that dose level; if none of these additional 3 participants developed a DLT, the next higher dose level was to be opened on that schedule. If >=2 participants experienced a first cycle DLT at the same dose level and schedule, that dose level was to be defined as the MAD for that schedule. No additional participants were to be entered at the MAD for that dosing schedule. DLT is defined in Outcome Measure 1.
Measured: Baseline up to 28 days
Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose Level (RP2D)
MTD was defined as the highest dose level studied for which the incidence of first cycle DLT was <33%. Once MTD was determined, it was defined as RP2D. DLT is defined in Outcome Measure 1.
Measured: Baseline up to 28 days
Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature
DLT is defined in Outcome Measure 1. Hematologic (Grade 4 [life-threatening or disabling]) and non-hematologic (Grade 3 [severe], 4 [life-threatening and disabling], 5 [resulting in death]) DLTs are reported separately. A single participant may experience more than one DLT. Both treatment-related and treatment-unrelated DLT events were reported for this outcome measure.
Measured: Baseline up to 28 days
Number of Participants With Treatment Emergent Adverse Events Categorized by Severity
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. For clinical description of nature (severity) of AEs, AEs were grades as: Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening or disabling AE; and Grade 5: death related to AE. AEs during Cycle 1 and AEs post Cycle 1 are reported separately.
Measured: Cycle 1, Cycle 2 up to 28 days after end of treatment (up to Cycle 93)
Number of Participants With Treatment-Related Treatment Emergent Adverse Events
A treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs during Cycle 1 and AEs post Cycle 1 are reported separately.
Measured: Cycle 1, Cycle 2 up to 28 days after end of treatment (up to Cycle 93)
Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness [to study drug] was assessed by the investigator (Yes/No).
Measured: Baseline up to 30 days after end of treatment (up to Cycle 93)
Maximum Observed Plasma Concentration (Cmax) on Day 1: Single Dose
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
Maximum Observed Plasma Concentration (Cmax) on Day 8: Multiple Dose
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
Maximum Observed Plasma Concentration (Cmax) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
The mean Cmax for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported.
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
Maximum Observed Plasma Concentration (Cmax) on Day 1: Food Effect
To determine the impact of food (specifically a high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In this crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. The first 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, the next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results are reported as per fed and fasted conditions. The high-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of the total caloric content.
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1: Single Dose
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 8: Multiple Dose
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
The median Tmax for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported.
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1: Food Effect
To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results are reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content.
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
Terminal Half-life (t½ ) on Day 1: Single Dose
Terminal half-life is the time measured for the plasma concentration to decrease by one half.
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
Terminal Half-life (t½ ) on Day 8: Multiple Dose
Terminal half-life is the time measured for the plasma concentration to decrease by one half.
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
Terminal Half-life (t½) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
Terminal half-life is the time measured for the plasma concentration to decrease by one half. The mean t1/2 for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported.
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
Terminal Half-life (t½ ) on Day 1: Food Effect
To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content.
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 1: Single Dose
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 8: Multiple Dose
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). The mean AUClast for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported.
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 1: Food Effect
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results are reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content.
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
Area Under the Curve From Time Zero to End of the Dosing Interval [AUC(0 to Tau)] on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
Area under the curve from time zero to end of the dosing interval (24 hours) [AUC (0-tau)]. The mean AUC (0-tau) for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported.
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] on Day 1: Single Dose
AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] on Day 8: Multiple Dose
AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] on Day 1: Food Effect
AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content.
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
Apparent Oral Clearance (CL/F) on Day 1: Single Dose
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
Apparent Oral Clearance (CL/F) on Day 8: Multiple Dose
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
Apparent Oral Clearance (CL/F) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
Clearance of a drug is a measure of rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. The mean CL/F for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported.
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
Apparent Oral Clearance (CL/F) on Day 1: Food Effect
Clearance of a drug is a measure of rate at which a drug is metabolized or eliminated by normal biological processes. To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content.
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
Apparent Volume of Distribution (Vz/F) on Day 1: Single Dose
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
Apparent Volume of Distribution (Vz/F) on Day 8: Multiple Dose
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
Apparent Volume of Distribution (Vz/F) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. The mean Vz/F for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported.
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
Apparent Volume of Distribution (Vz/F) on Day 1: Food Effect
Volume of distribution: theoretical volume in which total amount of drug would need to be uniformly distributed to produce desired plasma concentration. To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content.
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
Accumulation Ratio (Rac) on Day 8: Multiple Dose
Rac at Day 8 = AUC (0-tau) at Day 8 divided by AUC (0-tau) at Day 1.
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, 10, and 24 hours post-dose on C1D1 and C1D8
Accumulation Ratio (Rac) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
Rac at Day 14/21 = AUC (0-tau) at Day 14/21 divided by AUC (0-tau) at Day 1. The mean Rac for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported.
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
Terminal Phase Rate Constant [Lambda (z)] on Day 1: Single Dose
Terminal phase rate constant is the absolute value of the slope of a linear regression during the terminal phase of the natural--logarithm transformed concentration--time profile.
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
Terminal Phase Rate Constant [Lambda (z)] on Day 8: Multiple Dose
Terminal phase rate constant is the absolute value of the slope of a linear regression during the terminal phase of the natural-logarithm transformed concentration-time profile.
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
Terminal Phase Rate Constant [Lambda (z)] on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
Terminal phase rate constant is the absolute value of the slope of a linear regression during the terminal phase of the natural-logarithm transformed concentration-time profile. The mean lambda (z) for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported.
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
Terminal Phase Rate Constant [Lambda (z)] on Day 1: Food Effect
Terminal phase rate constant: absolute value of slope of a linear regression during terminal phase of natural-logarithm transformed concentration-time profile. To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content.
Measured: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
Cumulative Amount of Drug Recovered Unchanged in the Urine (Ae): Single Dose
Ae is the cumulative amount of drug recovered unchanged in urine over the 10 hour collection interval. Cumulative amount was calculated as sum of urine drug concentration in sample volume for each collection interval. Urine PK analysis was performed only in the MTD/RP2D groups (125 mg [21/28 Days] and 200 mg [14/21 Days]).
Measured: Hour 0 (pre-dose) to 10 hours post-dose on C1D1
Cumulative Amount of Drug Recovered Unchanged in the Urine (Ae): Food Effect
The Ae is defined in Outcome Measure 42. To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content.
Measured: Hour 0 (pre-dose) to 10 hours post-dose on C1D1
Percent Dose Recovered Unchanged in Urine (Percent Ae): Single Dose
Percent of dose recovered unchanged in urine over the 10 hour collection interval=100*(Ae divided by dose). Ae is the cumulative amount of drug recovered unchanged in urine over the 10 hour collection interval. Cumulative amount was calculated as sum of urine drug concentration in sample volume for each collection interval.
Measured: Hour 0 (pre-dose) to 10 hours post-dose on C1D1
Percent Dose Recovered Unchanged (Percent Ae) in Urine: Food Effect
The percent Ae is defined in Outcome Measure 44. To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content.
Measured: Hour 0 (pre-dose) to 10 hours post-dose on C1D1
Number of Participants With Best Response
Number of participants with best response. Complete response (CR): disappearance of all target and non-target lesions. Partial Response (PR): >=30% decrease in sum of longest diameter (LD) of lesions taking as reference baseline sum LD and no unequivocal progression in non-target lesions. Progressive disease (PD): >=20% increase in sum of LD of lesions taking as a reference smallest sum of the LD since treatment start, or the appearance of >=1 new lesion or unequivocal progression of existing non-target lesions. Stable disease (SD): neither shrinkage for PR nor increase for PD taking as reference smallest sum of LD since treatment start. SD was assessed following the first 2 cycles of treatment (>=2 cycles), 4 cycles of treatment (>=4 cycles), and 10 cycles of treatment (>=10 cycles). Participants may be reported in more than 1 category of SD. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response.
Measured: Baseline up to end of treatment, assessed at C1D1, C1D8, C1D15, C1D22, thereafter Day 1, 8, 15, and 22 of every other cycle up to end of treatment (up to Cycle 93)
Inhibition of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) Based on Phosphorylated Retinoblastoma (p-Rb) in Tumor Tissue
Phosphorylation of the retinoblastoma (Rb) protein by Cdk4/6 is typically required for human cancer cell proliferation. Tumor biopsies were to be performed, to demonstrate inhibition of Cdk4/6 based on reduction in phosphorylated Rb (p-Rb) in tumor tissue and p-Rb levels (fold decrease) were to be reported.
Measured: Baseline, C1D1, C1D8, C1D15, C1D22, thereafter Day 1, 8, 15, and 22 of every other cycle up to end of treatment (up to Cycle 93)
Correlation of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) With PD 0322991 Dose
Phosphorylation of the retinoblastoma (Rb) protein by Cdk4/6 is typically required for human cancer cell proliferation. Tumor biopsies were to be performed, to demonstrate inhibition of Cdk4/6 based on reduction in phosphorylated Rb (p-Rb) in tumor tissue, in correlation with respect to PD 0322991 dose.
Measured: Baseline, C1D1, C1D8, C1D15, C1D22, thereafter Day 1, 8, 15, and 22 of every other cycle up to end of treatment (up to Cycle 93)
Correlation of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) With Exposure
Phosphorylation of the retinoblastoma (Rb) protein by Cdk4/6 is typically required for human cancer cell proliferation. Tumor biopsies were to be performed, to demonstrate inhibition of Cdk4/6 based on reduction in phosphorylated Rb (p-Rb) in tumor tissue, in correlation with PD 0322991 exposure.
Measured: Baseline, C1D1, C1D8, C1D15, C1D22, thereafter Day 1, 8, 15, and 22 of every other cycle up to end of treatment (up to Cycle 93)
Correlation of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) With Tumor Response
Phosphorylation of the retinoblastoma (Rb) protein by Cdk4/6 is typically required for human cancer cell proliferation. Tumor biopsies were to be performed, to demonstrate inhibition of Cdk4/6 based on reduction in phosphorylated Rb (p-Rb) in tumor tissue, in correlation with tumor response.
Measured: Baseline, C1D1, C1D8, C1D15, C1D22, thereafter Day 1, 8, 15, and 22 of every other cycle up to end of treatment (up to Cycle 93)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2005 (estimated)
- Study startSep 2004
- Primary completionJul 2008
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00141297
- Sponsor's protocol ID
- A5481001
- Status last verified
- Dec 2015
- First submitted
- 30 Aug 2005
- Last updated
- 5 Jan 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009 Mar;9(3):153-66. doi: 10.1038/nrc2602.
PubMed 19238148Vaughn DJ, Flaherty K, Lal P, Gallagher M, O'Dwyer P, Wilner K, Chen I, Schwartz G. Treatment of growing teratoma syndrome. N Engl J Med. 2009 Jan 22;360(4):423-4. doi: 10.1056/NEJMc0808558. No abstract available.
PubMed 19164198
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Clinical, Pharmacokinetic, And Pharmacodynamic Evaluation Of 2 Schedules Of Oral PD 0332991, A Cyclin-Dependent Kinase Inhibitor, In Patients With Advanced Cancer
- ClinicalTrials.gov ID
- NCT00141297
- Acronym / sponsor ID
- A5481001
- Conditions
- Neoplasms, Lymphoma, Non-Hodgkin
- Keywords
- Advanced cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- Sep 2004
- Primary completion
- Jul 2008 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 1 Sep 2005 (estimated)
- Results
- Posted 28 Oct 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
PD-0332991 may work in cancer by stopping cancer cells from multiplying. PD-0332991 is in a new class of drugs called cyclin-dependent kinase (CDK inhibitors). This research study is the first time that PD-0332991 will be given to people. PD-0332991 is taken by mouth daily.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PD-0332991 | Experimental | Drug: PD-0332991 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Advanced solid tumors (excluding SCLC and retinoblastoma) or follicular of diffuse large cell non-Hodgkin's lymphoma, histologically or cytologically proven at diagnosis which is refractory to or intolerant of established therapy know to provide clinical benefit for their condition; tumors must express Rb
- Adequate blood cell counts, kidney function and liver function and and ECOG score of 0, 1, or 2.
- Patients may have to have tumor biopsy before and after treatment.
Key exclusion criteria (3 listed)
- Prior stem cell or bone marrow transplant
- Uncontrolled infection, unstable or sever intercurrent medical condition, or current drug or alcohol abuse
- Active or unstable cardiac disease or history of heart attack within 6 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PD-0332991Dose ranging study - evaluating two oral schedule: (1) 3/1 Schedule - PD-0332991 administered days 1-21 of a 28-day schedule, doses ranging from 25 to 150 mg once daily; (2) 2/1 Schedule - PD-0332991 administered days 1-14 of a 21-days schedule, doses ranging from 100 to 225 mg once daily | Drug | PD-0332991 |
Primary outcome
Number of Participants With Dose-Limiting Toxicities (DLT)
Time frame: Baseline up to 28 days
DLT: an adverse event occurring after initiation of PD 0332991 that met any following criteria: 1) Grade 4 hematologic toxicity (platelets less than [<] 25000 per microliter (mcL), absolute neutrophil count [ANC] <500/mcL, hemoglobin [Hb] <6.5 gram per deciliter [g/dL]; 2) ANC <1000/mcL associated with documented infection or fever greater than or equal to (>=) 38.5 degrees Celsius; 3) >=Grade 3 non-hematologic treatment-related toxicity. In an asymptomatic participant, Grade 3 corrected QT (QTc) prolongation (>500 millisecond) (only if persisted with repeat testing and after correction of reversible causes [electrolyte abnormalities or hypoxia]); and 4) Inability to receive next dose of PD 0332991 within 1 week (+/-1 day) of last dose due to lack of hematologic recovery (platelets <50000/mcL, ANC <1000/mcL, and Hb <8.0 g/dL) or due to prolonged non-hematologic toxicities of >=Grade 3 severity. Occurrence of a DLT necessitated immediate interruption of scheduled study treatment.
Maximum Administered Dose (MAD)
Time frame: Baseline up to 28 days
Three new evaluable participants were to be assessed at each new dose level. The minimum time that these participants were to be followed after starting treatment was 1 cycle (28 or 21 days) before a new dose level could be opened. If none of these 3 participants experienced a DLT, the next higher dose level was to be opened on that schedule. If 1 participant developed a DLT, 3 more evaluable participants were to be enrolled at that dose level; if none of these additional 3 participants developed a DLT, the next higher dose level was to be opened on that schedule. If >=2 participants experienced a first cycle DLT at the same dose level and schedule, that dose level was to be defined as the MAD for that schedule. No additional participants were to be entered at the MAD for that dosing schedule. DLT is defined in Outcome Measure 1.
Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose Level (RP2D)
Time frame: Baseline up to 28 days
MTD was defined as the highest dose level studied for which the incidence of first cycle DLT was <33%. Once MTD was determined, it was defined as RP2D. DLT is defined in Outcome Measure 1.
Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature
Time frame: Baseline up to 28 days
DLT is defined in Outcome Measure 1. Hematologic (Grade 4 [life-threatening or disabling]) and non-hematologic (Grade 3 [severe], 4 [life-threatening and disabling], 5 [resulting in death]) DLTs are reported separately. A single participant may experience more than one DLT. Both treatment-related and treatment-unrelated DLT events were reported for this outcome measure.
Number of Participants With Treatment Emergent Adverse Events Categorized by Severity
Time frame: Cycle 1, Cycle 2 up to 28 days after end of treatment (up to Cycle 93)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. For clinical description of nature (severity) of AEs, AEs were grades as: Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening or disabling AE; and Grade 5: death related to AE. AEs during Cycle 1 and AEs post Cycle 1 are reported separately.
Number of Participants With Treatment-Related Treatment Emergent Adverse Events
Time frame: Cycle 1, Cycle 2 up to 28 days after end of treatment (up to Cycle 93)
A treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs during Cycle 1 and AEs post Cycle 1 are reported separately.
Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug
Time frame: Baseline up to 30 days after end of treatment (up to Cycle 93)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness [to study drug] was assessed by the investigator (Yes/No).
Maximum Observed Plasma Concentration (Cmax) on Day 1: Single Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
Maximum Observed Plasma Concentration (Cmax) on Day 8: Multiple Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
Maximum Observed Plasma Concentration (Cmax) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
The mean Cmax for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported.
Maximum Observed Plasma Concentration (Cmax) on Day 1: Food Effect
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
To determine the impact of food (specifically a high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In this crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. The first 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, the next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results are reported as per fed and fasted conditions. The high-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of the total caloric content.
Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1: Single Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 8: Multiple Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
The median Tmax for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported.
Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1: Food Effect
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results are reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content.
Terminal Half-life (t½ ) on Day 1: Single Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
Terminal half-life is the time measured for the plasma concentration to decrease by one half.
Terminal Half-life (t½ ) on Day 8: Multiple Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
Terminal half-life is the time measured for the plasma concentration to decrease by one half.
Terminal Half-life (t½) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
Terminal half-life is the time measured for the plasma concentration to decrease by one half. The mean t1/2 for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported.
Terminal Half-life (t½ ) on Day 1: Food Effect
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content.
Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 1: Single Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 8: Multiple Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). The mean AUClast for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported.
Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 1: Food Effect
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results are reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content.
Area Under the Curve From Time Zero to End of the Dosing Interval [AUC(0 to Tau)] on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
Area under the curve from time zero to end of the dosing interval (24 hours) [AUC (0-tau)]. The mean AUC (0-tau) for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported.
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] on Day 1: Single Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] on Day 8: Multiple Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] on Day 1: Food Effect
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content.
Apparent Oral Clearance (CL/F) on Day 1: Single Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Apparent Oral Clearance (CL/F) on Day 8: Multiple Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Apparent Oral Clearance (CL/F) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
Clearance of a drug is a measure of rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. The mean CL/F for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported.
Apparent Oral Clearance (CL/F) on Day 1: Food Effect
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
Clearance of a drug is a measure of rate at which a drug is metabolized or eliminated by normal biological processes. To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content.
Apparent Volume of Distribution (Vz/F) on Day 1: Single Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Apparent Volume of Distribution (Vz/F) on Day 8: Multiple Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Apparent Volume of Distribution (Vz/F) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. The mean Vz/F for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported.
Apparent Volume of Distribution (Vz/F) on Day 1: Food Effect
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
Volume of distribution: theoretical volume in which total amount of drug would need to be uniformly distributed to produce desired plasma concentration. To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content.
Accumulation Ratio (Rac) on Day 8: Multiple Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10, and 24 hours post-dose on C1D1 and C1D8
Rac at Day 8 = AUC (0-tau) at Day 8 divided by AUC (0-tau) at Day 1.
Accumulation Ratio (Rac) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
Rac at Day 14/21 = AUC (0-tau) at Day 14/21 divided by AUC (0-tau) at Day 1. The mean Rac for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported.
Terminal Phase Rate Constant [Lambda (z)] on Day 1: Single Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
Terminal phase rate constant is the absolute value of the slope of a linear regression during the terminal phase of the natural--logarithm transformed concentration--time profile.
Terminal Phase Rate Constant [Lambda (z)] on Day 8: Multiple Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
Terminal phase rate constant is the absolute value of the slope of a linear regression during the terminal phase of the natural-logarithm transformed concentration-time profile.
Terminal Phase Rate Constant [Lambda (z)] on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
Terminal phase rate constant is the absolute value of the slope of a linear regression during the terminal phase of the natural-logarithm transformed concentration-time profile. The mean lambda (z) for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported.
Terminal Phase Rate Constant [Lambda (z)] on Day 1: Food Effect
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
Terminal phase rate constant: absolute value of slope of a linear regression during terminal phase of natural-logarithm transformed concentration-time profile. To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content.
Cumulative Amount of Drug Recovered Unchanged in the Urine (Ae): Single Dose
Time frame: Hour 0 (pre-dose) to 10 hours post-dose on C1D1
Ae is the cumulative amount of drug recovered unchanged in urine over the 10 hour collection interval. Cumulative amount was calculated as sum of urine drug concentration in sample volume for each collection interval. Urine PK analysis was performed only in the MTD/RP2D groups (125 mg [21/28 Days] and 200 mg [14/21 Days]).
Cumulative Amount of Drug Recovered Unchanged in the Urine (Ae): Food Effect
Time frame: Hour 0 (pre-dose) to 10 hours post-dose on C1D1
The Ae is defined in Outcome Measure 42. To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content.
Percent Dose Recovered Unchanged in Urine (Percent Ae): Single Dose
Time frame: Hour 0 (pre-dose) to 10 hours post-dose on C1D1
Percent of dose recovered unchanged in urine over the 10 hour collection interval=100*(Ae divided by dose). Ae is the cumulative amount of drug recovered unchanged in urine over the 10 hour collection interval. Cumulative amount was calculated as sum of urine drug concentration in sample volume for each collection interval.
Percent Dose Recovered Unchanged (Percent Ae) in Urine: Food Effect
Time frame: Hour 0 (pre-dose) to 10 hours post-dose on C1D1
The percent Ae is defined in Outcome Measure 44. To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content.
Number of Participants With Best Response
Time frame: Baseline up to end of treatment, assessed at C1D1, C1D8, C1D15, C1D22, thereafter Day 1, 8, 15, and 22 of every other cycle up to end of treatment (up to Cycle 93)
Number of participants with best response. Complete response (CR): disappearance of all target and non-target lesions. Partial Response (PR): >=30% decrease in sum of longest diameter (LD) of lesions taking as reference baseline sum LD and no unequivocal progression in non-target lesions. Progressive disease (PD): >=20% increase in sum of LD of lesions taking as a reference smallest sum of the LD since treatment start, or the appearance of >=1 new lesion or unequivocal progression of existing non-target lesions. Stable disease (SD): neither shrinkage for PR nor increase for PD taking as reference smallest sum of LD since treatment start. SD was assessed following the first 2 cycles of treatment (>=2 cycles), 4 cycles of treatment (>=4 cycles), and 10 cycles of treatment (>=10 cycles). Participants may be reported in more than 1 category of SD. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response.
Inhibition of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) Based on Phosphorylated Retinoblastoma (p-Rb) in Tumor Tissue
Time frame: Baseline, C1D1, C1D8, C1D15, C1D22, thereafter Day 1, 8, 15, and 22 of every other cycle up to end of treatment (up to Cycle 93)
Phosphorylation of the retinoblastoma (Rb) protein by Cdk4/6 is typically required for human cancer cell proliferation. Tumor biopsies were to be performed, to demonstrate inhibition of Cdk4/6 based on reduction in phosphorylated Rb (p-Rb) in tumor tissue and p-Rb levels (fold decrease) were to be reported.
Correlation of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) With PD 0322991 Dose
Time frame: Baseline, C1D1, C1D8, C1D15, C1D22, thereafter Day 1, 8, 15, and 22 of every other cycle up to end of treatment (up to Cycle 93)
Phosphorylation of the retinoblastoma (Rb) protein by Cdk4/6 is typically required for human cancer cell proliferation. Tumor biopsies were to be performed, to demonstrate inhibition of Cdk4/6 based on reduction in phosphorylated Rb (p-Rb) in tumor tissue, in correlation with respect to PD 0322991 dose.
Correlation of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) With Exposure
Time frame: Baseline, C1D1, C1D8, C1D15, C1D22, thereafter Day 1, 8, 15, and 22 of every other cycle up to end of treatment (up to Cycle 93)
Phosphorylation of the retinoblastoma (Rb) protein by Cdk4/6 is typically required for human cancer cell proliferation. Tumor biopsies were to be performed, to demonstrate inhibition of Cdk4/6 based on reduction in phosphorylated Rb (p-Rb) in tumor tissue, in correlation with PD 0322991 exposure.
Correlation of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) With Tumor Response
Time frame: Baseline, C1D1, C1D8, C1D15, C1D22, thereafter Day 1, 8, 15, and 22 of every other cycle up to end of treatment (up to Cycle 93)
Phosphorylation of the retinoblastoma (Rb) protein by Cdk4/6 is typically required for human cancer cell proliferation. Tumor biopsies were to be performed, to demonstrate inhibition of Cdk4/6 based on reduction in phosphorylated Rb (p-Rb) in tumor tissue, in correlation with tumor response.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 19238148Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009 Mar;9(3):153-66. doi: 10.1038/nrc2602.
- Derived from this study: PubMed 19164198Vaughn DJ, Flaherty K, Lal P, Gallagher M, O'Dwyer P, Wilner K, Chen I, Schwartz G. Treatment of growing teratoma syndrome. N Engl J Med. 2009 Jan 22;360(4):423-4. doi: 10.1056/NEJMc0808558. No abstract available.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PD-0332991 in people with Neoplasms and Lymphoma, Non-Hodgkin, run by Pfizer at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Oct 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose-Limiting Toxicities (DLT) (time frame: Baseline up to 28 days). The study lists 50 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00141297, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2016.