Clinical trial NCT02764151: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Oligodendroglioma
Astrocytoma
Malignant Glioma
Keywords: GBM
malignant glioma
glioma
anaplastic glioma
astrocytoma
IDO
IDO1
PF-06840003
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2016-05-06
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety and tolerability of increasing doses of PF-06840003 in patients with malignant gliomas.


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

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs) [Part 1]
timeFrame: Baseline to Day 28
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Part 1]
timeFrame: Baseline up to 1 year
measure: 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]
timeFrame: Baseline up to 1 year
Secondary outcomes:
measure: Objective Response Rate (ORR) [Part 1]
timeFrame: Weeks 8, 16, and 24
measure: Disease Control Rate (DCR) Based on the Immunotherapy Response Assessment for Neuro-Oncology (iRANO) Criteria [Part 1]
timeFrame: Weeks 8, 16, and 24
measure: 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]
timeFrame: Baseline up to 1 year
measure: 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]
timeFrame: Baseline up to 1 year
measure: Number of Participants With Clinically Significant Findings in Vital Signs [Part 1]
timeFrame: Baseline up to 1 year
measure: Single Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1]
timeFrame: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
measure: Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1]
timeFrame: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
measure: 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]
timeFrame: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
measure: Single Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1]
timeFrame: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
measure: Single Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1]
timeFrame: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
measure: Single Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1]
timeFrame: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
measure: Single Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1]
timeFrame: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
measure: 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]
timeFrame: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
measure: Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1]
timeFrame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
measure: Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1]
timeFrame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
measure: Multiple Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1]
timeFrame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
measure: Multiple Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1]
timeFrame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
measure: Multiple Dose: Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06840002 and PF-06840001 [Part 1]
timeFrame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
measure: Multiple Dose: Average Concentration for the Dosing Interval (Cav) of PF-06840002 and PF-06840001 [Part 1]
timeFrame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
measure: Multiple Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1]
timeFrame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
measure: Multiple Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1]
timeFrame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
measure: Multiple Dose: Observed Accumulation Ratio (Rac) of PF-06840002 and PF-06840001 [Part 1]
timeFrame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
measure: Multiple Dose: Steady State Accumulation Ratio (Rss) of PF-06840002 and PF-06840001 [Part 1]
timeFrame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
measure: Steady-State Trough Level Ratio [Part 1]
timeFrame: Baseline and Day 15
measure: Plasma Kynurenine and Tryptophan [Part 1]
timeFrame: 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
measure: Plasma Endogenous Kynurenine/Tryptophan Ratio [Part 1]
timeFrame: 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
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Clinical & Translational Research Center
state: California
city: Los Angeles
country: United States
facility: UCLA Oncology Center
state: California
city: Los Angeles
country: United States
facility: UCLA School of Medicine
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Albuquerque
country: United States
facility: University of New Mexico Comprehensive Cancer Center
state: New Mexico
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: CUMC Research Pharmacy
state: New York
city: Tarrytown
country: United States
facility: Columbia Doctors Tarrytown
state: New York
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center, Duke Cancer Center
state: North Carolina
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
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.
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.