Back to resultsFirst in Patient Study for PF-06840003 in Malignant Gliomas
Primary Purpose
Oligodendroglioma, Astrocytoma, Malignant Glioma
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PF-06840003
Sponsored by
About this trial
This is an interventional treatment trial for Oligodendroglioma focused on measuring GBM, malignant glioma, glioma, anaplastic glioma, astrocytoma, IDO, IDO1, PF-06840003
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Sites / Locations
- Ronald Reagan UCLA Medical Center
- UCLA Clinical & Translational Research Center
- UCLA Oncology Center
- UCLA School of Medicine
- Massachusetts General Hospital
- Brigham & Women's Hospital
- Dana-Farber Cancer Institute
- University of New Mexico Comprehensive Cancer Center
- Columbia University Medical Center
- Columbia University Medical Center
- CUMC Research Pharmacy
- Columbia Doctors Tarrytown
- Duke Cancer Center
- Duke University Medical Center, Duke Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
PF-06840003
Arm Description
Daily Oral PF-06840003
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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).
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.
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.
Plasma Kynurenine and Tryptophan [Part 1]
The levels of Kynurenine and Tryptophan in blood samples were determined using the qualified analytical method.
Plasma Endogenous Kynurenine/Tryptophan Ratio [Part 1]
The Kynurenine/Tryptophan ratio was determined by 1000*Kynurenine/Tryptophan.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02764151
Brief Title
First in Patient Study for PF-06840003 in Malignant Gliomas
Official Title
A PHASE 1 DOSE ESCALATION STUDY EVALUATING THE SAFETY AND TOLERABILITY OF PF-06840003 IN PATIENTS WITH MALIGNANT GLIOMAS
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Terminated
Why Stopped
Sponsor decided to prematurely terminate the study and not to pursue marketing approval for the indication of malignant glioma.
Study Start Date
September 9, 2016 (Actual)
Primary Completion Date
December 26, 2018 (Actual)
Study Completion Date
December 26, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will evaluate the safety and tolerability of increasing doses of PF-06840003 in patients with malignant gliomas.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oligodendroglioma, Astrocytoma, Malignant Glioma
Keywords
GBM, malignant glioma, glioma, anaplastic glioma, astrocytoma, IDO, IDO1, PF-06840003
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
17 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PF-06840003
Arm Type
Experimental
Arm Description
Daily Oral PF-06840003
Intervention Type
Drug
Intervention Name(s)
PF-06840003
Intervention Description
Daily Oral PF-06840003
Primary Outcome Measure Information:
Title
Number of Participants With Dose Limiting Toxicities (DLTs) [Part 1]
Description
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.
Time Frame
Baseline to Day 28
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Part 1]
Description
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.
Time Frame
Baseline up to 1 year
Title
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]
Description
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.
Time Frame
Baseline up to 1 year
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR) [Part 1]
Description
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.
Time Frame
Weeks 8, 16, and 24
Title
Disease Control Rate (DCR) Based on the Immunotherapy Response Assessment for Neuro-Oncology (iRANO) Criteria [Part 1]
Description
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.
Time Frame
Weeks 8, 16, and 24
Title
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]
Description
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.
Time Frame
Baseline up to 1 year
Title
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]
Description
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.
Time Frame
Baseline up to 1 year
Title
Number of Participants With Clinically Significant Findings in Vital Signs [Part 1]
Description
Vital signs included measurements of blood pressure and temperature (oral, tympanic, temporal or axillary). The investigator judged any clinically significant vital signs findings.
Time Frame
Baseline up to 1 year
Title
Single Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1]
Description
Cmax of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) were observed directly from data.
Time Frame
Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Title
Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1]
Description
Tmax of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) were observed directly from data as time of first occurence.
Time Frame
Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Title
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]
Description
AUClast of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by linear/log trapezoidal method.
Time Frame
Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Title
Single Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1]
Description
AUCtau of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by linear/log trapezoidal method.
Time Frame
Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Title
Single Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1]
Description
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.
Time Frame
Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Title
Single Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1]
Description
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.
Time Frame
Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Title
Single Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1]
Description
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.
Time Frame
Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Title
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]
Description
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.
Time Frame
Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Title
Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1]
Description
Cmax of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) were observed directly from data.
Time Frame
Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Title
Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1]
Description
Tmax of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) were observed directly from data as time of first occurence.
Time Frame
Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Title
Multiple Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1]
Description
AUCtau of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by linear/log trapezoidal method.
Time Frame
Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Title
Multiple Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1]
Description
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.
Time Frame
Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Title
Multiple Dose: Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06840002 and PF-06840001 [Part 1]
Description
Cmin of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was observed directly from data.
Time Frame
Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Title
Multiple Dose: Average Concentration for the Dosing Interval (Cav) of PF-06840002 and PF-06840001 [Part 1]
Description
Cav of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was observed directly from data.
Time Frame
Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Title
Multiple Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1]
Description
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).
Time Frame
Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Title
Multiple Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1]
Description
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.
Time Frame
Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Title
Multiple Dose: Observed Accumulation Ratio (Rac) of PF-06840002 and PF-06840001 [Part 1]
Description
Rac of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by AUCtau (steady state) / AUCtau (single dose).
Time Frame
Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Title
Multiple Dose: Steady State Accumulation Ratio (Rss) of PF-06840002 and PF-06840001 [Part 1]
Description
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.
Time Frame
Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Title
Steady-State Trough Level Ratio [Part 1]
Description
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.
Time Frame
Baseline and Day 15
Title
Plasma Kynurenine and Tryptophan [Part 1]
Description
The levels of Kynurenine and Tryptophan in blood samples were determined using the qualified analytical method.
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
Title
Plasma Endogenous Kynurenine/Tryptophan Ratio [Part 1]
Description
The Kynurenine/Tryptophan ratio was determined by 1000*Kynurenine/Tryptophan.
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Ronald Reagan UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-6894
Country
United States
Facility Name
UCLA Clinical & Translational Research Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
UCLA Oncology Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
UCLA School of Medicine
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Brigham & Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of New Mexico Comprehensive Cancer Center
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87102
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10019
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
CUMC Research Pharmacy
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Columbia Doctors Tarrytown
City
Tarrytown
State/Province
New York
ZIP/Postal Code
10591
Country
United States
Facility Name
Duke Cancer Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Duke University Medical Center, Duke Cancer Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
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.
Citations:
PubMed Identifier
32436060
Citation
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.
Results Reference
derived
PubMed Identifier
30232146
Citation
Gomes 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.
Results Reference
derived
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=C0591001
Description
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Learn more about this trial
First in Patient Study for PF-06840003 in Malignant Gliomas
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