OligodendrogliomaPhase 1NCT02764151
First in Patient Study for PF-06840003 in Malignant Gliomas
A Phase 1 study testing PF-06840003 in people with Oligodendroglioma and Astrocytoma, run by Pfizer at 14 sites in United States.
Trial summary
This study will evaluate the safety and tolerability of increasing doses of PF-06840003 in patients with malignant gliomas. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Oligodendroglioma, Astrocytoma, Malignant Glioma
- What is being tested?
- PF-06840003
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 14 sitesUnited States
- Study dates
- 9 Sep 2016to 26 Dec 2018
- 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
- Diagnosis of WHO Grade IV glioblastoma or WHO Grade III anaplastic gliomas
- For patients with Grade IV GBM, recurrent disease at the time of the first or second recurrence or progression. For patients with Grade III anaplastic gliomas, recurrent disease at the time of at least a first recurrence but no more than a fourth recurrence or progression
- Karnofsky performance score greater than or equal to 70%
- Adequate bone marrow, kidney and liver function
Who cannot join
- History of CNS bleeding within 6 months of registration
- Previous anti-angiogenics or anti-vascular endothelial growth factor within 12 months of registration
- Requires treatment with high dose systemic corticosteroids defined as >2 mg/day
- Radiation therapy within 12 weeks of registration
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
University of New Mexico Comprehensive Cancer Center
Albuquerque, New Mexico, 87102
Massachusetts General Hospital
Boston, Massachusetts, 02114
Brigham & Women's Hospital
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Duke Cancer Center
Durham, North Carolina, 27710
Duke University Medical Center, Duke Cancer Center
Durham, North Carolina, 27710
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095-6894
UCLA Clinical & Translational Research Center
Los Angeles, California, 90095
UCLA Oncology Center
Los Angeles, California, 90095
UCLA School of Medicine
Los Angeles, California, 90095
Columbia University Medical Center
New York, New York, 10019
Columbia University Medical Center
New York, New York, 10032
CUMC Research Pharmacy
New York, New York, 10032
Columbia Doctors Tarrytown
Tarrytown, New York, 10591
About this study
Official title: A PHASE 1 DOSE ESCALATION STUDY EVALUATING THE SAFETY AND TOLERABILITY OF PF-06840003 IN PATIENTS WITH MALIGNANT GLIOMAS
This study will evaluate the safety and tolerability of increasing doses of PF-06840003 in patients with malignant gliomas.
- Conditions
- Oligodendroglioma, Astrocytoma, Malignant Glioma
- Being tested
- PF-06840003
- Keywords
- GBM, malignant glioma, glioma, anaplastic glioma, astrocytoma, IDO, IDO1, PF-06840003
- Medical subject headings
- Oligodendroglioma, Astrocytoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PF-06840003Drug
Daily Oral PF-06840003
| Study group | Role | What they receive |
|---|---|---|
| PF-06840003 | Experimental | Daily Oral PF-06840003 Receives: Drug: PF-06840003 |
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) [Part 1]
DLTs: Any of the following adverse events (AE) occurring in the first cycle of treatment, unless there is a clear alternative explanation. Hematologic: Grade (Gr) 4 neutropenia lasting >=5 days; febrile neutropenia; Gr>=3 neutropenic with infection; Gr>=3 thrombocytopenia with bleeding; Gr 4 thrombocytopenia. Non-Hematologic: Any toxicity attributable to PF-06840003 that resulted in administration of less than 80% of the planned doses during Cycle 1; Gr 4 non-hematologic AE; Gr 3 AE lasting >7 days despite optimal supportive care; Gr 3 central nervous system (CNS) AE regardless of duration; Gr 3 QTc prolongation (QTc >500 milliseconds) (a DLT only if persisting after correction of any reversible causes); Concurrent aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3*upper limit of normal (ULN) and total bilirubin >2*ULN.
Measured: Baseline to Day 28
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Part 1]
An AE was any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were those with initial onset or increasing in severity after the first dose of study treatment.
Measured: Baseline up to 1 year
Number of Participants With TEAEs by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1]
Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03: Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
Measured: Baseline up to 1 year
Secondary outcomes (26)
Objective Response Rate (ORR) [Part 1]
Objective response rate (ORR), defined as the percentage of patients achieving complete response (CR) or partial response (PR) as assessed by Macdonald criteria: CR: complete disappearance of all enhancing measurable and non-measurable disease on consecutive MRI at least 4 weeks apart, off steroid, sustained for at least 4 weeks; PR: >=50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks.
Measured: Weeks 8, 16, and 24
Disease Control Rate (DCR) Based on the Immunotherapy Response Assessment for Neuro-Oncology (iRANO) Criteria [Part 1]
Disease control rate (DCR) was defined as the percentage of patients achieving CR, PR, or stable disease (SD). Overall DCR was based on iRANO criteria: CR: complete disappearance of all enhancing measurable and non-measurable disease on consecutive MRI at least 4 weeks apart, off steroid, sustained for at least 4 weeks; PR: >=50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks; SD: does not qualify for CR, PR, or progression disease, and stable clinically.
Measured: Weeks 8, 16, and 24
Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1]
Following parameters were analyzed for hematology laboratory test: hemoglobin, platelets, white blood cell (WBC), absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils, and absolute basophils. Laboratory abnormalities were graded per NCI CTCAE version 4.03 and those with at least 1 participant are presented here.
Measured: Baseline up to 1 year
Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1]
Following parameters were analyzed for chemistry laboratory test: Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), alkaline phosphatase, sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen (BUN) or urea, creatinine, uric acid, glucose (non-fasted), albumin, and phosphorous or phosphate. Laboratory abnormalities were graded per NCI CTCAE version 4.03 and those with at least 1 participant are presented here.
Measured: Baseline up to 1 year
Number of Participants With Clinically Significant Findings in Vital Signs [Part 1]
Vital signs included measurements of blood pressure and temperature (oral, tympanic, temporal or axillary). The investigator judged any clinically significant vital signs findings.
Measured: Baseline up to 1 year
Single Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1]
Cmax of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) were observed directly from data.
Measured: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1]
Tmax of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) were observed directly from data as time of first occurence.
Measured: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Single Dose: Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-06840002 and PF-06840001 [Part 1]
AUClast of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by linear/log trapezoidal method.
Measured: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Single Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1]
AUCtau of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by linear/log trapezoidal method.
Measured: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Single Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1]
CL/F of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by Dose/Area under the concentration-time profile from time 0 extrapolated to infinite time (AUCinf). The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
Measured: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Single Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1]
Vz/F of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by Dose/(AUC*kel). AUC is the area under concentration curve and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve. The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
Measured: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Single Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1]
t1/2 of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear concentration-time curve. Only those data points judged to describe the terminal log linear decline were used in the regression. The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
Measured: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Single Dose: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06840002 and PF-06840001 [Part 1]
AUCinf of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by AUClast + (Clast/kel), where AUClast is the area under the concentration-time profile from time zero to the time of the last quantifiable concentration, Clast is the predicted serum concentration at the last quantifiable time point estimated from the log linear regression analysis and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve. The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
Measured: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1]
Cmax of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) were observed directly from data.
Measured: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1]
Tmax of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) were observed directly from data as time of first occurence.
Measured: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Multiple Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1]
AUCtau of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by linear/log trapezoidal method.
Measured: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Multiple Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1]
t1/2 of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear concentration-time curve. Only those data points judged to describe the terminal log linear decline were used in the regression. The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
Measured: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Multiple Dose: Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06840002 and PF-06840001 [Part 1]
Cmin of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was observed directly from data.
Measured: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Multiple Dose: Average Concentration for the Dosing Interval (Cav) of PF-06840002 and PF-06840001 [Part 1]
Cav of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was observed directly from data.
Measured: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Multiple Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1]
CL/F of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by Dose/Area under the concentration-time profile from time 0 extrapolated to infinite time (AUCinf).
Measured: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Multiple Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1]
Vz/F of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by Dose/(AUC*kel). AUC is the area under concentration curve and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve. The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
Measured: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Multiple Dose: Observed Accumulation Ratio (Rac) of PF-06840002 and PF-06840001 [Part 1]
Rac of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by AUCtau (steady state) / AUCtau (single dose).
Measured: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Multiple Dose: Steady State Accumulation Ratio (Rss) of PF-06840002 and PF-06840001 [Part 1]
Rss of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by AUCtau (steady state) / AUCinf (single dose). The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
Measured: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Steady-State Trough Level Ratio [Part 1]
Steady-State trough level ratio was determined by cerebrospinal fluid (CSF)/Plasma. CSF/Plasma ratio was calculated based on the unbound concentration of each analyte. The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
Measured: Baseline and Day 15
Plasma Kynurenine and Tryptophan [Part 1]
The levels of Kynurenine and Tryptophan in blood samples were determined using the qualified analytical method.
Measured: Cycle 1 Day 1 pre-dose, and 1, 2, 4, 6, 8, 24 hours post-dose; Cycle 1 Day 4 and Day 8 pre-dose; Cycle 1 Day 15 pre-dose, and 1, 2, 4, 6, 8, 24 hours post-dose
Plasma Endogenous Kynurenine/Tryptophan Ratio [Part 1]
The Kynurenine/Tryptophan ratio was determined by 1000*Kynurenine/Tryptophan.
Measured: Cycle 1 Day 1 pre-dose, and 1, 2, 4, 6, 8, 24 hours post-dose; Cycle 1 Day 4 and Day 8 pre-dose; Cycle 1 Day 15 pre-dose, and 1, 2, 4, 6, 8, 24 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2016 (estimated)
- Study start9 Sep 2016
- Primary completion26 Dec 2018
- Study completion26 Dec 2018
Why it stopped: Sponsor decided to prematurely terminate the study and not to pursue marketing approval for the indication of malignant glioma.
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 OligodendrogliomaStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 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
- NCT02764151
- Sponsor's protocol ID
- C0591001
- Status last verified
- Jan 2020
- First submitted
- 27 Apr 2016
- Last updated
- 27 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
Publications
Reardon DA, Desjardins A, Rixe O, Cloughesy T, Alekar S, Williams JH, Li R, Taylor CT, Lassman AB. A phase 1 study of PF-06840003, an oral indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor in patients with recurrent malignant glioma. Invest New Drugs. 2020 Dec;38(6):1784-1795. doi: 10.1007/s10637-020-00950-1. Epub 2020 May 20.
PubMed 32436060Gomes B, Driessens G, Bartlett D, Cai D, Cauwenberghs S, Crosignani S, Dalvie D, Denies S, Dillon CP, Fantin VR, Guo J, Letellier MC, Li W, Maegley K, Marillier R, Miller N, Pirson R, Rabolli V, Ray C, Streiner N, Torti VR, Tsaparikos K, Van den Eynde BJ, Wythes M, Yao LC, Zheng X, Tumang J, Kraus M. Characterization of the Selective Indoleamine 2,3-Dioxygenase-1 (IDO1) Catalytic Inhibitor EOS200271/PF-06840003 Supports IDO1 as a Critical Resistance Mechanism to PD-(L)1 Blockade Therapy. Mol Cancer Ther. 2018 Dec;17(12):2530-2542. doi: 10.1158/1535-7163.MCT-17-1104. Epub 2018 Sep 19.
PubMed 30232146
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A PHASE 1 DOSE ESCALATION STUDY EVALUATING THE SAFETY AND TOLERABILITY OF PF-06840003 IN PATIENTS WITH MALIGNANT GLIOMAS
- ClinicalTrials.gov ID
- NCT02764151
- Acronym / sponsor ID
- C0591001
- Conditions
- Oligodendroglioma, Astrocytoma, Malignant Glioma
- Keywords
- GBM, malignant glioma, glioma, anaplastic glioma, astrocytoma, IDO, IDO1, PF-06840003
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decided to prematurely terminate the study and not to pursue marketing approval for the indication of malignant glioma.
- Enrolment
- 17 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- 9 Sep 2016 (actual)
- Primary completion
- 26 Dec 2018 (actual)
- Study completion
- 26 Dec 2018 (actual)
- First posted
- 6 May 2016 (estimated)
- Results
- Posted 27 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the safety and tolerability of increasing doses of PF-06840003 in patients with malignant gliomas.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PF-06840003 | Experimental | Drug: PF-06840003Daily Oral PF-06840003 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis of WHO Grade IV glioblastoma or WHO Grade III anaplastic gliomas
- For patients with Grade IV GBM, recurrent disease at the time of the first or second recurrence or progression. For patients with Grade III anaplastic gliomas, recurrent disease at the time of at least a first recurrence but no more than a fourth recurrence or progression
- Karnofsky performance score greater than or equal to 70%
- Adequate bone marrow, kidney and liver function
Key exclusion criteria (4 listed)
- History of CNS bleeding within 6 months of registration
- Previous anti-angiogenics or anti-vascular endothelial growth factor within 12 months of registration
- Requires treatment with high dose systemic corticosteroids defined as >2 mg/day
- Radiation therapy within 12 weeks of registration
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 |
|---|---|---|
| PF-06840003Daily Oral PF-06840003 | Drug | PF-06840003 |
Primary outcome
Number of Participants With Dose Limiting Toxicities (DLTs) [Part 1]
Time frame: Baseline to Day 28
DLTs: Any of the following adverse events (AE) occurring in the first cycle of treatment, unless there is a clear alternative explanation. Hematologic: Grade (Gr) 4 neutropenia lasting >=5 days; febrile neutropenia; Gr>=3 neutropenic with infection; Gr>=3 thrombocytopenia with bleeding; Gr 4 thrombocytopenia. Non-Hematologic: Any toxicity attributable to PF-06840003 that resulted in administration of less than 80% of the planned doses during Cycle 1; Gr 4 non-hematologic AE; Gr 3 AE lasting >7 days despite optimal supportive care; Gr 3 central nervous system (CNS) AE regardless of duration; Gr 3 QTc prolongation (QTc >500 milliseconds) (a DLT only if persisting after correction of any reversible causes); Concurrent aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3*upper limit of normal (ULN) and total bilirubin >2*ULN.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Part 1]
Time frame: Baseline up to 1 year
An AE was any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were those with initial onset or increasing in severity after the first dose of study treatment.
Number of Participants With TEAEs by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1]
Time frame: Baseline up to 1 year
Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03: Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
26 secondary outcomes
Objective Response Rate (ORR) [Part 1]
Time frame: Weeks 8, 16, and 24
Disease Control Rate (DCR) Based on the Immunotherapy Response Assessment for Neuro-Oncology (iRANO) Criteria [Part 1]
Time frame: Weeks 8, 16, and 24
Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1]
Time frame: Baseline up to 1 year
Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1]
Time frame: Baseline up to 1 year
Number of Participants With Clinically Significant Findings in Vital Signs [Part 1]
Time frame: Baseline up to 1 year
Single Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1]
Time frame: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1]
Time frame: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Single Dose: Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-06840002 and PF-06840001 [Part 1]
Time frame: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Single Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1]
Time frame: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Single Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1]
Time frame: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Single Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1]
Time frame: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Single Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1]
Time frame: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Single Dose: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06840002 and PF-06840001 [Part 1]
Time frame: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1]
Time frame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1]
Time frame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Multiple Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1]
Time frame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Multiple Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1]
Time frame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Multiple Dose: Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06840002 and PF-06840001 [Part 1]
Time frame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Multiple Dose: Average Concentration for the Dosing Interval (Cav) of PF-06840002 and PF-06840001 [Part 1]
Time frame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Multiple Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1]
Time frame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Multiple Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1]
Time frame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Multiple Dose: Observed Accumulation Ratio (Rac) of PF-06840002 and PF-06840001 [Part 1]
Time frame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Multiple Dose: Steady State Accumulation Ratio (Rss) of PF-06840002 and PF-06840001 [Part 1]
Time frame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Steady-State Trough Level Ratio [Part 1]
Time frame: Baseline and Day 15
Plasma Kynurenine and Tryptophan [Part 1]
Time frame: Cycle 1 Day 1 pre-dose, and 1, 2, 4, 6, 8, 24 hours post-dose; Cycle 1 Day 4 and Day 8 pre-dose; Cycle 1 Day 15 pre-dose, and 1, 2, 4, 6, 8, 24 hours post-dose
Plasma Endogenous Kynurenine/Tryptophan Ratio [Part 1]
Time frame: Cycle 1 Day 1 pre-dose, and 1, 2, 4, 6, 8, 24 hours post-dose; Cycle 1 Day 4 and Day 8 pre-dose; Cycle 1 Day 15 pre-dose, and 1, 2, 4, 6, 8, 24 hours post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32436060Reardon DA, Desjardins A, Rixe O, Cloughesy T, Alekar S, Williams JH, Li R, Taylor CT, Lassman AB. A phase 1 study of PF-06840003, an oral indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor in patients with recurrent malignant glioma. Invest New Drugs. 2020 Dec;38(6):1784-1795. doi: 10.1007/s10637-020-00950-1. Epub 2020 May 20.
- Derived from this study: PubMed 30232146Gomes B, Driessens G, Bartlett D, Cai D, Cauwenberghs S, Crosignani S, Dalvie D, Denies S, Dillon CP, Fantin VR, Guo J, Letellier MC, Li W, Maegley K, Marillier R, Miller N, Pirson R, Rabolli V, Ray C, Streiner N, Torti VR, Tsaparikos K, Van den Eynde BJ, Wythes M, Yao LC, Zheng X, Tumang J, Kraus M. Characterization of the Selective Indoleamine 2,3-Dioxygenase-1 (IDO1) Catalytic Inhibitor EOS200271/PF-06840003 Supports IDO1 as a Critical Resistance Mechanism to PD-(L)1 Blockade Therapy. Mol Cancer Ther. 2018 Dec;17(12):2530-2542. doi: 10.1158/1535-7163.MCT-17-1104. Epub 2018 Sep 19.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: No. Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
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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
14 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 PF-06840003 in people with Oligodendroglioma and Astrocytoma, run by Pfizer at 14 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 4 inclusion and 4 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: stopped early, as of the sponsor's last update on 27 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 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 27 Jan 2020). 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 (DLTs) [Part 1] (time frame: Baseline to Day 28). The study lists 3 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 NCT02764151, 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 27 Jan 2020.