NeoplasmsPhase 1NCT01362374
Safety and Clinical Pharmacology of GDC-0068 in Combination With Docetaxel, Fluoropyrimidine Plus Oxaliplatin, Paclitaxel, or Enzalutamide in Participants With Advanced Solid Tumors
A Phase 1 study testing 5-FU, Docetaxel and Enzalutamide in people with Neoplasms, run by Genentech, Inc. at 11 sites in 4 countries.
Trial summary
This is an open-label, multicenter, Phase Ib, dose-escalation study designed to assess the safety, tolerability, and pharmacokinetics of oral ipatasertib (GDC-0068) administered in combination with either docetaxel (Arm A), or oxaliplatin, leucovorin, 5-fluorouracil (5-FU) (mFOLFOX6 chemotherapy) (Arm B), or… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- 5-FU, Docetaxel and Enzalutamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 122 participants
- Where
- 11 sitesin 4 countries
- Study dates
- 11 Jul 2011to 16 Oct 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening
- Histologically or cytologically documented advanced or metastatic solid tumors for which established therapy either does not exist or has proven ineffective or intolerable
- Life expectancy greater than or equal to (>=) 12 weeks
- Adequate hematologic and end organ function
- For female participants of childbearing potential and male participants with partners of childbearing potential, agreement (by participant and/or partner) to use highly effective forms of contraception and to continue its use for the duration of the study and for 4 months after last dose of study treatment (for females) and 6 months after last dose of study treatment (for males)
Who cannot join
- Prior anti-cancer therapy that fulfills the following criteria: a total of more than three (Arms A and B) or two (Arms C and D) prior cytotoxic chemotherapy regimens, high-dose chemotherapy requiring stem-cell support, and irradiation to >=25 percent (%) of bone marrow-bearing areas
- Treatment with chemotherapy, hormonal therapy (except hormone replacement therapy, oral contraceptives, or gonadotropin-releasing hormone (GnRH) agonists or antagonists for prostate cancer), immunotherapy, biologic therapy, radiation therapy (except palliative radiation to bony metastases), or herbal therapy as cancer therapy within 4 weeks prior to initiation of ipatasertib. Exceptions are kinase inhibitors approved by local regulatory authorities, which may be used within 2 weeks prior to initiation of ipatasertib, provided that any clinically-relevant drug-related toxicity has completely resolved and prior approval is obtained from the Medical Monitor
- Palliative radiation to bony metastases within 2 weeks prior to initiation of ipatasertib
- History of Type 1 or Type 2 diabetes requiring regular medication
- Grade >= 2 heart failure or history of unstable angina
- History of clinically significant ventricular arrhythmias or active ventricular arrhythmia requiring medication
- For Arm D only: History of seizure, unexplained loss of consciousness, transient ischemic attack within 12 months of enrollment, cerebral vascular accident, and any brain metastases
Trial locations and contacts
11 sites in 4 countries.
11 sites in 4 countries
United States7 sites
University Of Michigan
Ann Arbor, Michigan, 48109
Massachusetts General Hospital
Boston, Massachusetts, 02114
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89128
SCRI
Nashville, Tennessee, 37203
Virginia Oncology Associates
Norfolk, Virginia, 23502
California Pacific Med Center
San Francisco, California, 94115
Florida Cancer Specialists - Sarasota
Sarasota, Florida, 34232
Spain2 sites
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital Clinico Universitario de Valencia
Valencia, 46010
France1 site
Institut Gustave Roussy; Departement Oncologie Medicale
Villejuif, 94805
About this study
Official title: A Phase Ib, Open-label, Dose-escalation Study of the Safety and Pharmacology of Ipatasertib (GDC-0068) in Combination With Docetaxel, Fluoropyrimidine Plus Oxaliplatin, Paclitaxel, or Enzalutamide in Patients With Advanced Solid Tumors
This is an open-label, multicenter, Phase Ib, dose-escalation study designed to assess the safety, tolerability, and pharmacokinetics of oral ipatasertib (GDC-0068) administered in combination with either docetaxel (Arm A), or oxaliplatin, leucovorin, 5-fluorouracil (5-FU) (mFOLFOX6 chemotherapy) (Arm B), or paclitaxel (Arm C), in participants with advanced or metastatic solid tumors for which standard therapy either does not exist or has proven ineffective or intolerable. Arm D will assess the safety, tolerability, and pharmacokinetics of ipatasertib administered in combination with enzalutamide in participants with metastatic castration-resistant prostate cancer (CRPC). There will be two stages within each arm of this study: a dose-escalation stage (Stage 1) and a cohort-expansion stage (Stage 2). In Stage 1, approximately 3 to 6 cohorts in Arms A and B and 1 to 2 cohorts in Arms C and D will be evaluated to determine the maximum tolerated dose (MTD) of ipatasertib in a given combination. Additional participants will be enrolled in Stage 2 (cohort expansion), to further characterize the safety and tolerability of ipatasertib in these combinations and to confirm a potential recommended Phase II dose of ipatasertib for each regimen.
NOTE: Arms A, B, and C are closed.
- Conditions
- Neoplasms
- Being tested
- 5-FU, Docetaxel, Enzalutamide, Ipatasertib, Leucovorin
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-FUDrug
Also called Adrucil
5-FU at a dose level of 400 mg/m^2 as intravenous (IV) injection followed by a dose of 2400 mg/m^2 as IV infusion over 46 hrs will be administered on Day 1 of each 14-day cycle until disease progression or unacceptable toxicity.
DocetaxelDrug
Docetaxel will be administered at dose level of 75 mg/m^2 as IV infusion over 1 hr on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.
EnzalutamideDrug
Enzalutamide will be administered orally at a dose level of 160 mg once daily continuously as per schedule defined in respective arm until disease progression or unacceptable toxicity.
IpatasertibDrug
Ipatasertib will be administered orally (in escalating doses during Stage 1 followed by at a dose decided during Stage 1) as per schedule defined in the respective arms.
LeucovorinDrug
Also called Wellcovorin
Leucovorin at a dose level of 400 mg/m^2 as IV infusion over 2 hrs will be administered on Day 1 of each 14-day cycle until disease progression or unacceptable toxicity.
OxaliplatinDrug
Also called Eloxatin
Oxaliplatin at a dose level of 85 mg/m^2 as IV infusion over 2 hours will be administered on Day 1 of each 14-day cycle until disease progression or unacceptable toxicity.
PaclitaxelDrug
Also called Taxol
Paclitaxel at a dose of 90 mg/m^2 as IV infusion over 1 hr will be administered on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity.
| Study group | Role | What they receive |
|---|---|---|
| Arm A (Doc + Ipat 100mg) | Experimental | Participants received ipatasertib at a dose of 100 milligrams (mg) once daily for 14 consecutive days (beginning on Day 2) in combination with docetaxel on Day 1, in 21-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. Receives: Drug: Docetaxel; Drug: Ipatasertib |
| Arm A (Doc + Ipat 200mg) | Experimental | Participants received ipatasertib at a dose of 200mg once daily for 14 consecutive days (beginning on Day 2) in combination with docetaxel on Day 1, in 21-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. Receives: Drug: Docetaxel; Drug: Ipatasertib |
| Arm A (Doc + Ipat 400mg) | Experimental | Participants received ipatasertib at a dose of 400mg once daily for 14 consecutive days (beginning on Day 2) in combination with docetaxel on Day 1, in 21-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. Receives: Drug: Docetaxel; Drug: Ipatasertib |
| Arm A (Doc + Ipat 600mg) | Experimental | Participants received ipatasertib at a dose of 600mg once daily for 14 consecutive days (beginning on Day 2) in combination with docetaxel on Day 1, in 21-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. Receives: Drug: Docetaxel; Drug: Ipatasertib |
| Arm B (mFOLFOX + Ipat 100mg) | Experimental | Participants received ipatasertib at a dose of 100mg once daily for 7 consecutive days (beginning on Day 1) in combination with mFOLFOX6 chemotherapy (comprising of oxaliplatin, leucovorin, and 5-FU) on Day 1, in 14-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. Receives: Drug: 5-FU; Drug: Ipatasertib; Drug: Leucovorin; Drug: Oxaliplatin |
| Arm B (mFOLFOX + Ipat 200mg) | Experimental | Participants received ipatasertib at a dose of 200mg once daily for 7 consecutive days (beginning on Day 1) in combination with mFOLFOX6 chemotherapy (comprising of oxaliplatin, leucovorin, and 5-FU) on Day 1, in 14-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. Receives: Drug: 5-FU; Drug: Ipatasertib; Drug: Leucovorin; Drug: Oxaliplatin |
| Arm B (mFOLFOX + Ipat 400mg) | Experimental | Participants received ipatasertib at a dose of 400mg once daily for 7 consecutive days (beginning on Day 1) in combination with mFOLFOX6 chemotherapy (comprising of oxaliplatin, leucovorin, and 5-FU) on Day 1, in 14-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. Receives: Drug: 5-FU; Drug: Ipatasertib; Drug: Leucovorin; Drug: Oxaliplatin |
| Arm B (mFOLFOX + Ipat 600mg) | Experimental | Participants received ipatasertib at a dose of 600mg once daily for 7 consecutive days (beginning on Day 1) in combination with mFOLFOX6 chemotherapy (comprising of oxaliplatin, leucovorin, and 5-FU) on Day 1, in 14-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. Receives: Drug: 5-FU; Drug: Ipatasertib; Drug: Leucovorin; Drug: Oxaliplatin |
| Arm C (Pac + Ipat 400mg) | Experimental | Participants received ipatasertib at a dose of 400mg once daily for 21 consecutive days (beginning on Day 1) in combination with paclitaxel on Days 1, 8, and 15, in 28-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. Receives: Drug: Ipatasertib; Drug: Paclitaxel |
| Arm C (Pac + Ipat 600mg) | Experimental | Participants received ipatasertib at a dose of 600mg once daily for 21 consecutive days (beginning on Day 1) in combination with paclitaxel on Days 1, 8, and 15, in 28-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. Receives: Drug: Ipatasertib; Drug: Paclitaxel |
| Arm D (Enza + Ipat 400mg) | Experimental | Participants received ipatasertib at a dose of 400mg once daily alone for 8 days, then from Day 9, ipatasertib will be administered in combination with enzalutamide once daily for 27 days (Cycle 1 duration = 35 days). Participants received both ipatasertib and enzalutamide once daily continuously in subsequent 28-days cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. Higher (up to 600 mg) or lower dose of ipatasertib may be evaluated in subsequent cycles depending upon safety, tolerability, and pharmacokinetics of the first cycle. Receives: Drug: Enzalutamide; Drug: Ipatasertib |
| Arm D (Enza + Ipat 600mg) | Experimental | Participants received ipatasertib at a dose of 600mg once daily alone for 8 days, then from Day 9, ipatasertib will be administered in combination with enzalutamide once daily for 27 days (Cycle 1 duration = 35 days). Participants received both ipatasertib and enzalutamide once daily continuously in subsequent 28-days cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. Higher (up to 600 mg) or lower dose of ipatasertib may be evaluated in subsequent cycles depending upon safety, tolerability, and pharmacokinetics of the first cycle. Receives: Drug: Enzalutamide; Drug: Ipatasertib |
| Arm D (Enza + Ipat 400-600mg) | Experimental | Participants received ipatasertib at a dose of 400-600mg once daily alone for 8 days, then from Day 9, ipatasertib will be administered in combination with enzalutamide once daily for 27 days (Cycle 1 duration = 35 days). Participants received both ipatasertib and enzalutamide once daily continuously in subsequent 28-days cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. Higher (up to 600 mg) or lower dose of ipatasertib may be evaluated in subsequent cycles depending upon safety, tolerability, and pharmacokinetics of the first cycle. Receives: Drug: Enzalutamide; Drug: Ipatasertib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Limiting Toxicities (DLTs)
Measured: Arm A: Days 2-21 of Cycle 1 (cycle length=21 days); Arm B: Days 1-14 of Cycles 1 and 2 (cycle length=14 days); Arm C: Days 1-28 of Cycle 1 (cycle length=28 days); Arm D: Days 1-35 of Cycle 1 (cycle length=28 days except for Cycle 1=35 days)
Maximum Tolerated Dose (MTD) of Ipatasertib
Measured: Arm A: Days 2-21 of Cycle 1 (cycle length=21 days); Arm B: Days 1-14 of Cycles 1 and 2 (cycle length=14 days); Arm C: Days 1-28 of Cycle 1 (cycle length=28 days); Arm D: Days 1-35 of Cycle 1 (cycle length=28 days except for Cycle 1=35 days)
Recommended Phase II Dose (RP2D) of Ipatasertib
Measured: Arm A: Days 2-21 of Cycle 1 (cycle length=21 days); Arm B: Days 1-14 of Cycles 1 and 2 (cycle length=14 days); Arm C: Days 1-28 of Cycle 1 (cycle length=28 days); Arm D: Days 1-35 of Cycle 1 (cycle length=28 days except for Cycle 1=35 days)
Number of Participants With Adverse Events (AEs)
Measured: Baseline up until 30 days following the last administration of study treatment or until initiation of another anti-cancer therapy, whichever occurs first (up to a maximum of 9.25 years).
Secondary outcomes (56)
Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Docetaxel (Arm A)
Measured: Immediately prior to docetaxel infusion, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours (hrs) after start of docetaxel infusion on Day 1 Cycles 1 and 2 (1 cycle=21 days)
Plasma Terminal Half-Life (t1/2) of Docetaxel (Arm A)
Measured: Immediately prior to docetaxel infusion, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours (hrs) after start of docetaxel infusion on Day 1 Cycles 1 and 2 (1 cycle=21 days)
Plasma Clearance (CL) of Docetaxel (Arm A)
Measured: Immediately prior to docetaxel infusion, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours (hrs) after start of docetaxel infusion on Day 1 Cycles 1 and 2 (1 cycle=21 days)
Volume of Distribution (Vz) of Docetaxel (Arm A)
Measured: Immediately prior to docetaxel infusion, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours (hrs) after start of docetaxel infusion on Day 1 Cycles 1 and 2 (1 cycle=21 days)
Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Total Platinum (Arm B)
Measured: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days)
Plasma Terminal Half-Life (t1/2) of Total Platinum (Arm B)
Measured: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days)
Plasma CL of Total Platinum (Arm B)
Measured: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days)
Vz of Total Platinum (Arm B)
Measured: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days)
Maximum Observed Plasma Concentration (Cmax) of Total Platinum (Arm B)
Measured: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days)
Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Free Platinum (Arm B)
Measured: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days)
Plasma Terminal Half-Life (t1/2) of Free Platinum (Arm B)
Measured: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days)
Plasma CL of Free Platinum (Arm B)
Measured: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days)
Vz of Free Platinum (Arm B)
Measured: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days)
Maximum Observed Plasma Concentration (Cmax) of Free Platinum (Arm B)
Measured: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days)
Cmax of 5-FU (Arm B)
Measured: 2, 2.25, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days)
Steady-State Concentration (Css) of 5-FU (Arm B)
Measured: 2, 2.25, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days)
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24]) of 5-FU (Arm B)
Measured: 2, 2.25, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days)
Cmax of Paclitaxel (Arm C)
Measured: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days)
Cmax of Paclitaxel Metabolite (Arm C)
Measured: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days)
AUC(0-inf) of Paclitaxel (Arm C)
Measured: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days)
AUC(0-inf) of Paclitaxel Metabolite (Arm C)
Measured: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days)
Plasma CL of Paclitaxel (Arm C)
Measured: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days)
Plasma CL of Paclitaxel Metabolite (Arm C)
Measured: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days)
Vz of Paclitaxel (Arm C)
Measured: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days)
Vz of Paclitaxel Metabolite (Arm C)
Measured: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days)
Plasma t1/2 of Paclitaxel (Arm C)
Measured: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days)
Plasma t1/2 of Paclitaxel Metabolite (Arm C)
Measured: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days)
AUC(0-24) of Enzalutamide (Arm D)
Measured: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days)
AUC(0-24) of Enzalutamide Metabolite (Arm D)
Measured: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days)
Time to Reach Cmax (Tmax) of Enzalutamide (Arm D)
Measured: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days)
Tmax of Enzalutamide Metabolite (Arm D)
Measured: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days)
Cmax at Steady State (Cmax,ss) of Enzalutamide (Arm D)
Measured: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days)
Cmax,ss of Enzalutamide Metabolite (Arm D)
Measured: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days)
AUC(0-24) of Ipatasertib (Arm D)
Measured: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days)
AUC(0-24) of Ipatasertib Metabolite (G037720) (Arm D)
Measured: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days)
Tmax of Ipatasertib (Arm D)
Measured: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days)
Tmax of Ipatasertib Metabolite (Arm D)
Measured: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days)
Cmax,ss of Ipatasertib (Arm D)
Measured: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days)
Cmax,ss of Ipatasertib Metabolite (Arm D)
Measured: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days)
Tmax of Ipatasertib (Arm A)
Measured: PRDS, 0.5, 1, 2, 3, 4, 6, 24 hrs PSDS on Day 2 Cycle 1 (1 cycle=21 days)
Tmax of Ipatasertib (Arm B)
Measured: PRDS, 0.5, 1, 2, 3, 4, 6, 24 hrs PSDS Day 1 Cycle 1 (1 cycle=14 days)
Tmax of Ipatasertib (Arm C)
Measured: PRDS, 1, 2, 3, 4, 6, 24 hrs PSDS Day 8 Cycle 1 (1 cycle=28 days)
Tmax of Ipatasertib Metabolite (Arm A)
Measured: PRDS, 0.5, 1, 2, 3, 4, 6, 24 hrs PSDS on Day 2 Cycle 1 (1 cycle=21 days)
Tmax of Ipatasertib Metabolite (Arm B)
Measured: PRDS, 0.5, 1, 2, 3, 4, 6, 24 hrs PSDS Day 1 Cycle 1 (1 cycle=14 days)
Tmax of Ipatasertib Metabolite (Arm C)
Measured: PRDS, 1, 2, 3, 4, 6, 24 hrs PSDS Day 8 Cycle 1 (cycles=21 days, Cycle 1=35 days)
Cmax,ss of Ipatasertib (Arm A)
Measured: PRDS, 0.5, 1, 2, 3, 4, 6, 24 hrs PSDS on Day 2 Cycle 1 (1 cycle=21 days)
Cmax,ss of Ipatasertib (Arm B)
Measured: PRDS, 0.5, 1, 2, 3, 4, 6, 24 hrs PSDS Day 1 Cycle 1 (1 cycle=14 days)
Cmax,ss of Ipatasertib (Arm C)
Measured: PRDS, 1, 2, 3, 4, 6, 24 hrs PSDS Day 8 Cycle 1 (1 cycle=28 days)
Cmax,ss of Ipatasertib Metabolite (Arm A)
Measured: PRDS, 0.5, 1, 2, 3, 4, 6, 24 hrs PSDS on Day 2 Cycle 1 (1 cycle=21 days)
Cmax,ss of Ipatasertib Metabolite (Arm B)
Measured: PRDS, 0.5, 1, 2, 3, 4, 6, 24 hrs PSDS Day 1 Cycle 1 (1 cycle=14 days)
Cmax,ss of Ipatasertib Metabolite (Arm C)
Measured: PRDS, 1, 2, 3, 4, 6, 24 hrs PSDS Day 8 Cycle 1 (1 cycle=28 days)
Number of Participants With Objective Response as Determined by Investigator Review of Tumor Assessments Using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Measured: Baseline up to disease progression or death, whichever occurs first (up to approximately 6 years)
Duration of Response (DOR) as Determined by Investigator Review of Tumor Assessments Using RECIST v1.1
Measured: Baseline up to disease progression or death, whichever occurs first (up to approximately 6 years)
Progression-free Survival (PFS) as Determined by Investigator Review of Tumor Assessments Using RECIST v1.1
Measured: Baseline up to disease progression or death, whichever occurs first (up to approximately 6 years)
Radiographic Progression-free Survival (rPFS) as Determined by Investigator (Arm D only)
Measured: Baseline up to radiographic disease progression or death, whichever occurs first (up to approximately 6 years)
Time to Treatment Failure (TTF)
Measured: Baseline up to treatment discontinuation for any reason (up to approximately 6 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2011 (estimated)
- Study start11 Jul 2011
- Primary completion16 Oct 2020
- Study completion16 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by Genentech, Inc.The 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 122 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genentech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Daniel Maslyar, M.D., Study director, Genentech, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01362374
- Sponsor's protocol ID
- PAM4983g
- Other IDs
- GO27845, 2011-000782-13
- Status last verified
- Jan 2022
- First submitted
- 26 May 2011
- Last updated
- 12 Jan 2022
- Results posted
- No
Publications
Isakoff SJ, Tabernero J, Molife LR, Soria JC, Cervantes A, Vogelzang NJ, Patel MR, Hussain M, Baron A, Argiles G, Conkling PR, Sampath D, Maslyar D, Patel P, Chan W, Gendreau S, Musib L, Xu N, Ma H, Lin K, Bendell J. Antitumor activity of ipatasertib combined with chemotherapy: results from a phase Ib study in solid tumors. Ann Oncol. 2020 May;31(5):626-633. doi: 10.1016/j.annonc.2020.02.007. Epub 2020 Feb 20.
PubMed 32205017
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib, Open-label, Dose-escalation Study of the Safety and Pharmacology of Ipatasertib (GDC-0068) in Combination With Docetaxel, Fluoropyrimidine Plus Oxaliplatin, Paclitaxel, or Enzalutamide in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT01362374
- Acronym / sponsor ID
- PAM4983g
- Conditions
- Neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 122 participants (actual)
- Lead sponsor
- Genentech, Inc.Industry (pharma, biotech, devices)
- Study start
- 11 Jul 2011 (actual)
- Primary completion
- 16 Oct 2020 (actual)
- Study completion
- 16 Oct 2020 (actual)
- First posted
- 30 May 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, multicenter, Phase Ib, dose-escalation study designed to assess the safety, tolerability, and pharmacokinetics of oral ipatasertib (GDC-0068) administered in combination with either docetaxel (Arm A), or oxaliplatin, leucovorin, 5-fluorouracil (5-FU) (mFOLFOX6 chemotherapy) (Arm B), or paclitaxel (Arm C), in participants with advanced or metastatic solid tumors for which standard therapy either does not exist or has proven ineffective or intolerable. Arm D will assess the safety, tolerability, and pharmacokinetics of ipatasertib administered in combination with enzalutamide in participants with metastatic castration-resistant prostate cancer (CRPC). There will be two stages within each arm of this study: a dose-escalation stage (Stage 1) and a cohort-expansion stage (Stage 2). In Stage 1, approximately 3 to 6 cohorts in Arms A and B and 1 to 2 cohorts in Arms C and D will be evaluated to determine the maximum tolerated dose (MTD) of ipatasertib in a given combination. Additional participants will be enrolled in Stage 2 (cohort expansion), to further characterize the safety and tolerability of ipatasertib in these combinations and to confirm a potential recommended Phase II dose of ipatasertib for each regimen.
NOTE: Arms A, B, and C are closed.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 13
| Arm | Type | Receives |
|---|---|---|
| Arm A (Doc + Ipat 100mg) | Experimental | Drug: Docetaxel, Drug: IpatasertibParticipants received ipatasertib at a dose of 100 milligrams (mg) once daily for 14 consecutive days (beginning on Day 2) in combination with docetaxel on Day 1, in 21-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. |
| Arm A (Doc + Ipat 200mg) | Experimental | Drug: Docetaxel, Drug: IpatasertibParticipants received ipatasertib at a dose of 200mg once daily for 14 consecutive days (beginning on Day 2) in combination with docetaxel on Day 1, in 21-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. |
| Arm A (Doc + Ipat 400mg) | Experimental | Drug: Docetaxel, Drug: IpatasertibParticipants received ipatasertib at a dose of 400mg once daily for 14 consecutive days (beginning on Day 2) in combination with docetaxel on Day 1, in 21-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. |
| Arm A (Doc + Ipat 600mg) | Experimental | Drug: Docetaxel, Drug: IpatasertibParticipants received ipatasertib at a dose of 600mg once daily for 14 consecutive days (beginning on Day 2) in combination with docetaxel on Day 1, in 21-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. |
| Arm B (mFOLFOX + Ipat 100mg) | Experimental | Drug: 5-FU, Drug: Ipatasertib, Drug: Leucovorin, Drug: OxaliplatinParticipants received ipatasertib at a dose of 100mg once daily for 7 consecutive days (beginning on Day 1) in combination with mFOLFOX6 chemotherapy (comprising of oxaliplatin, leucovorin, and 5-FU) on Day 1, in 14-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. |
| Arm B (mFOLFOX + Ipat 200mg) | Experimental | Drug: 5-FU, Drug: Ipatasertib, Drug: Leucovorin, Drug: OxaliplatinParticipants received ipatasertib at a dose of 200mg once daily for 7 consecutive days (beginning on Day 1) in combination with mFOLFOX6 chemotherapy (comprising of oxaliplatin, leucovorin, and 5-FU) on Day 1, in 14-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. |
| Arm B (mFOLFOX + Ipat 400mg) | Experimental | Drug: 5-FU, Drug: Ipatasertib, Drug: Leucovorin, Drug: OxaliplatinParticipants received ipatasertib at a dose of 400mg once daily for 7 consecutive days (beginning on Day 1) in combination with mFOLFOX6 chemotherapy (comprising of oxaliplatin, leucovorin, and 5-FU) on Day 1, in 14-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. |
| Arm B (mFOLFOX + Ipat 600mg) | Experimental | Drug: 5-FU, Drug: Ipatasertib, Drug: Leucovorin, Drug: OxaliplatinParticipants received ipatasertib at a dose of 600mg once daily for 7 consecutive days (beginning on Day 1) in combination with mFOLFOX6 chemotherapy (comprising of oxaliplatin, leucovorin, and 5-FU) on Day 1, in 14-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. |
| Arm C (Pac + Ipat 400mg) | Experimental | Drug: Ipatasertib, Drug: PaclitaxelParticipants received ipatasertib at a dose of 400mg once daily for 21 consecutive days (beginning on Day 1) in combination with paclitaxel on Days 1, 8, and 15, in 28-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. |
| Arm C (Pac + Ipat 600mg) | Experimental | Drug: Ipatasertib, Drug: PaclitaxelParticipants received ipatasertib at a dose of 600mg once daily for 21 consecutive days (beginning on Day 1) in combination with paclitaxel on Days 1, 8, and 15, in 28-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. |
| Arm D (Enza + Ipat 400mg) | Experimental | Drug: Enzalutamide, Drug: IpatasertibParticipants received ipatasertib at a dose of 400mg once daily alone for 8 days, then from Day 9, ipatasertib will be administered in combination with enzalutamide once daily for 27 days (Cycle 1 duration = 35 days). Participants received both ipatasertib and enzalutamide once daily continuously in subsequent 28-days cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. Higher (up to 600 mg) or lower dose of ipatasertib may be evaluated in subsequent cycles depending upon safety, tolerability, and pharmacokinetics of the first cycle. |
| Arm D (Enza + Ipat 600mg) | Experimental | Drug: Enzalutamide, Drug: IpatasertibParticipants received ipatasertib at a dose of 600mg once daily alone for 8 days, then from Day 9, ipatasertib will be administered in combination with enzalutamide once daily for 27 days (Cycle 1 duration = 35 days). Participants received both ipatasertib and enzalutamide once daily continuously in subsequent 28-days cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. Higher (up to 600 mg) or lower dose of ipatasertib may be evaluated in subsequent cycles depending upon safety, tolerability, and pharmacokinetics of the first cycle. |
| Arm D (Enza + Ipat 400-600mg) | Experimental | Drug: Enzalutamide, Drug: IpatasertibParticipants received ipatasertib at a dose of 400-600mg once daily alone for 8 days, then from Day 9, ipatasertib will be administered in combination with enzalutamide once daily for 27 days (Cycle 1 duration = 35 days). Participants received both ipatasertib and enzalutamide once daily continuously in subsequent 28-days cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. Higher (up to 600 mg) or lower dose of ipatasertib may be evaluated in subsequent cycles depending upon safety, tolerability, and pharmacokinetics of the first cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening
- Histologically or cytologically documented advanced or metastatic solid tumors for which established therapy either does not exist or has proven ineffective or intolerable
- Life expectancy greater than or equal to (>=) 12 weeks
- Adequate hematologic and end organ function
- For female participants of childbearing potential and male participants with partners of childbearing potential, agreement (by participant and/or partner) to use highly effective forms of contraception and to continue its use for the duration of the study and for 4 months after last dose of study treatment (for females) and 6 months after last dose of study treatment (for males)
Key exclusion criteria (7 listed)
- Prior anti-cancer therapy that fulfills the following criteria: a total of more than three (Arms A and B) or two (Arms C and D) prior cytotoxic chemotherapy regimens, high-dose chemotherapy requiring stem-cell support, and irradiation to >=25 percent (%) of bone marrow-bearing areas
- Treatment with chemotherapy, hormonal therapy (except hormone replacement therapy, oral contraceptives, or gonadotropin-releasing hormone (GnRH) agonists or antagonists for prostate cancer), immunotherapy, biologic therapy, radiation therapy (except palliative radiation to bony metastases), or herbal therapy as cancer therapy within 4 weeks prior to initiation of ipatasertib. Exceptions are kinase inhibitors approved by local regulatory authorities, which may be used within 2 weeks prior to initiation of ipatasertib, provided that any clinically-relevant drug-related toxicity has completely resolved and prior approval is obtained from the Medical Monitor
- Palliative radiation to bony metastases within 2 weeks prior to initiation of ipatasertib
- History of Type 1 or Type 2 diabetes requiring regular medication
- Grade >= 2 heart failure or history of unstable angina
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 |
|---|---|---|
| 5-FUAlso: Adrucil5-FU at a dose level of 400 mg/m^2 as intravenous (IV) injection followed by a dose of 2400 mg/m^2 as IV infusion over 46 hrs will be administered on Day 1 of each 14-day cycle until disease progression or unacceptable toxicity. | Drug | Arm B (mFOLFOX + Ipat 100mg), Arm B (mFOLFOX + Ipat 200mg), Arm B (mFOLFOX + Ipat 400mg), Arm B (mFOLFOX + Ipat 600mg) |
| DocetaxelDocetaxel will be administered at dose level of 75 mg/m^2 as IV infusion over 1 hr on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity. | Drug | Arm A (Doc + Ipat 100mg), Arm A (Doc + Ipat 200mg), Arm A (Doc + Ipat 400mg), Arm A (Doc + Ipat 600mg) |
| EnzalutamideEnzalutamide will be administered orally at a dose level of 160 mg once daily continuously as per schedule defined in respective arm until disease progression or unacceptable toxicity. | Drug | Arm D (Enza + Ipat 400-600mg), Arm D (Enza + Ipat 400mg), Arm D (Enza + Ipat 600mg) |
| IpatasertibIpatasertib will be administered orally (in escalating doses during Stage 1 followed by at a dose decided during Stage 1) as per schedule defined in the respective arms. | Drug | Arm A (Doc + Ipat 100mg), Arm A (Doc + Ipat 200mg), Arm A (Doc + Ipat 400mg), Arm A (Doc + Ipat 600mg), Arm B (mFOLFOX + Ipat 100mg), Arm B (mFOLFOX + Ipat 200mg), Arm B (mFOLFOX + Ipat 400mg), Arm B (mFOLFOX + Ipat 600mg), Arm C (Pac + Ipat 400mg), Arm C (Pac + Ipat 600mg), Arm D (Enza + Ipat 400-600mg), Arm D (Enza + Ipat 400mg), Arm D (Enza + Ipat 600mg) |
| LeucovorinAlso: WellcovorinLeucovorin at a dose level of 400 mg/m^2 as IV infusion over 2 hrs will be administered on Day 1 of each 14-day cycle until disease progression or unacceptable toxicity. | Drug | Arm B (mFOLFOX + Ipat 100mg), Arm B (mFOLFOX + Ipat 200mg), Arm B (mFOLFOX + Ipat 400mg), Arm B (mFOLFOX + Ipat 600mg) |
| OxaliplatinAlso: EloxatinOxaliplatin at a dose level of 85 mg/m^2 as IV infusion over 2 hours will be administered on Day 1 of each 14-day cycle until disease progression or unacceptable toxicity. | Drug | Arm B (mFOLFOX + Ipat 100mg), Arm B (mFOLFOX + Ipat 200mg), Arm B (mFOLFOX + Ipat 400mg), Arm B (mFOLFOX + Ipat 600mg) |
| PaclitaxelAlso: TaxolPaclitaxel at a dose of 90 mg/m^2 as IV infusion over 1 hr will be administered on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity. | Drug | Arm C (Pac + Ipat 400mg), Arm C (Pac + Ipat 600mg) |
Primary outcome
Number of Participants With Dose Limiting Toxicities (DLTs)
Time frame: Arm A: Days 2-21 of Cycle 1 (cycle length=21 days); Arm B: Days 1-14 of Cycles 1 and 2 (cycle length=14 days); Arm C: Days 1-28 of Cycle 1 (cycle length=28 days); Arm D: Days 1-35 of Cycle 1 (cycle length=28 days except for Cycle 1=35 days)
Maximum Tolerated Dose (MTD) of Ipatasertib
Time frame: Arm A: Days 2-21 of Cycle 1 (cycle length=21 days); Arm B: Days 1-14 of Cycles 1 and 2 (cycle length=14 days); Arm C: Days 1-28 of Cycle 1 (cycle length=28 days); Arm D: Days 1-35 of Cycle 1 (cycle length=28 days except for Cycle 1=35 days)
Recommended Phase II Dose (RP2D) of Ipatasertib
Time frame: Arm A: Days 2-21 of Cycle 1 (cycle length=21 days); Arm B: Days 1-14 of Cycles 1 and 2 (cycle length=14 days); Arm C: Days 1-28 of Cycle 1 (cycle length=28 days); Arm D: Days 1-35 of Cycle 1 (cycle length=28 days except for Cycle 1=35 days)
Number of Participants With Adverse Events (AEs)
Time frame: Baseline up until 30 days following the last administration of study treatment or until initiation of another anti-cancer therapy, whichever occurs first (up to a maximum of 9.25 years).
56 secondary outcomes
Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Docetaxel (Arm A)
Time frame: Immediately prior to docetaxel infusion, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours (hrs) after start of docetaxel infusion on Day 1 Cycles 1 and 2 (1 cycle=21 days)
Plasma Terminal Half-Life (t1/2) of Docetaxel (Arm A)
Time frame: Immediately prior to docetaxel infusion, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours (hrs) after start of docetaxel infusion on Day 1 Cycles 1 and 2 (1 cycle=21 days)
Plasma Clearance (CL) of Docetaxel (Arm A)
Time frame: Immediately prior to docetaxel infusion, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours (hrs) after start of docetaxel infusion on Day 1 Cycles 1 and 2 (1 cycle=21 days)
Volume of Distribution (Vz) of Docetaxel (Arm A)
Time frame: Immediately prior to docetaxel infusion, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours (hrs) after start of docetaxel infusion on Day 1 Cycles 1 and 2 (1 cycle=21 days)
Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Total Platinum (Arm B)
Time frame: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days)
Plasma Terminal Half-Life (t1/2) of Total Platinum (Arm B)
Time frame: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days)
Plasma CL of Total Platinum (Arm B)
Time frame: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days)
Vz of Total Platinum (Arm B)
Time frame: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days)
Maximum Observed Plasma Concentration (Cmax) of Total Platinum (Arm B)
Time frame: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days)
Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Free Platinum (Arm B)
Time frame: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days)
Plasma Terminal Half-Life (t1/2) of Free Platinum (Arm B)
Time frame: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days)
Plasma CL of Free Platinum (Arm B)
Time frame: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days)
Vz of Free Platinum (Arm B)
Time frame: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days)
Maximum Observed Plasma Concentration (Cmax) of Free Platinum (Arm B)
Time frame: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days)
Cmax of 5-FU (Arm B)
Time frame: 2, 2.25, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days)
Steady-State Concentration (Css) of 5-FU (Arm B)
Time frame: 2, 2.25, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days)
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24]) of 5-FU (Arm B)
Time frame: 2, 2.25, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days)
Cmax of Paclitaxel (Arm C)
Time frame: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days)
Cmax of Paclitaxel Metabolite (Arm C)
Time frame: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days)
AUC(0-inf) of Paclitaxel (Arm C)
Time frame: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days)
AUC(0-inf) of Paclitaxel Metabolite (Arm C)
Time frame: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days)
Plasma CL of Paclitaxel (Arm C)
Time frame: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days)
Plasma CL of Paclitaxel Metabolite (Arm C)
Time frame: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days)
Vz of Paclitaxel (Arm C)
Time frame: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days)
Vz of Paclitaxel Metabolite (Arm C)
Time frame: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days)
Plasma t1/2 of Paclitaxel (Arm C)
Time frame: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days)
Plasma t1/2 of Paclitaxel Metabolite (Arm C)
Time frame: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days)
AUC(0-24) of Enzalutamide (Arm D)
Time frame: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days)
AUC(0-24) of Enzalutamide Metabolite (Arm D)
Time frame: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days)
Time to Reach Cmax (Tmax) of Enzalutamide (Arm D)
Time frame: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days)
Tmax of Enzalutamide Metabolite (Arm D)
Time frame: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days)
Cmax at Steady State (Cmax,ss) of Enzalutamide (Arm D)
Time frame: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days)
Cmax,ss of Enzalutamide Metabolite (Arm D)
Time frame: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days)
AUC(0-24) of Ipatasertib (Arm D)
Time frame: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days)
AUC(0-24) of Ipatasertib Metabolite (G037720) (Arm D)
Time frame: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days)
Tmax of Ipatasertib (Arm D)
Time frame: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days)
Tmax of Ipatasertib Metabolite (Arm D)
Time frame: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days)
Cmax,ss of Ipatasertib (Arm D)
Time frame: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days)
Cmax,ss of Ipatasertib Metabolite (Arm D)
Time frame: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days)
Tmax of Ipatasertib (Arm A)
Time frame: PRDS, 0.5, 1, 2, 3, 4, 6, 24 hrs PSDS on Day 2 Cycle 1 (1 cycle=21 days)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2022.
- Derived from this study: PubMed 32205017Isakoff SJ, Tabernero J, Molife LR, Soria JC, Cervantes A, Vogelzang NJ, Patel MR, Hussain M, Baron A, Argiles G, Conkling PR, Sampath D, Maslyar D, Patel P, Chan W, Gendreau S, Musib L, Xu N, Ma H, Lin K, Bendell J. Antitumor activity of ipatasertib combined with chemotherapy: results from a phase Ib study in solid tumors. Ann Oncol. 2020 May;31(5):626-633. doi: 10.1016/j.annonc.2020.02.007. Epub 2020 Feb 20.
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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.
Daniel Maslyar, M.D. study director
Genentech, Inc.
11 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 5-FU, Docetaxel and Enzalutamide in people with Neoplasms, run by Genentech, Inc. at 11 sites in 4 countries.
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 5 inclusion and 7 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 12 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Spain, France, United Kingdom. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 (DLTs) (time frame: Arm A: Days 2-21 of Cycle 1 (cycle length=21 days); Arm B: Days 1-14 of Cycles 1 and 2 (cycle length=14 days); Arm C: Days 1-28 of Cycle 1 (cycle length=28 days); Arm D: Days 1-35 of Cycle 1 (cycle length=28 days except for Cycle 1=35 days)). The study lists 4 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 NCT01362374, which also lists 1 linked publication.
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 12 Jan 2022.