NCT02764151

Brief Summary

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

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
17

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Sep 2016

Typical duration for phase_1

Geographic Reach
1 country

14 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 27, 2016

Completed
9 days until next milestone

First Posted

Study publicly available on registry

May 6, 2016

Completed
4 months until next milestone

Study Start

First participant enrolled

September 9, 2016

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 26, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 26, 2018

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

January 27, 2020

Completed
Last Updated

January 27, 2020

Status Verified

January 1, 2020

Enrollment Period

2.3 years

First QC Date

April 27, 2016

Results QC Date

December 2, 2019

Last Update Submit

January 13, 2020

Conditions

OligodendrogliomaAstrocytomaMalignant Glioma

Keywords

GBMmalignant gliomagliomaanaplastic gliomaastrocytomaIDOIDO1PF-06840003

Outcome Measures

Primary Outcomes (3)

  • 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.

    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.

    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.

    Baseline up to 1 year

Secondary Outcomes (26)

  • Objective Response Rate (ORR) [Part 1]

    Weeks 8, 16, and 24

  • Disease Control Rate (DCR) Based on the Immunotherapy Response Assessment for Neuro-Oncology (iRANO) Criteria [Part 1]

    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]

    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]

    Baseline up to 1 year

  • Number of Participants With Clinically Significant Findings in Vital Signs [Part 1]

    Baseline up to 1 year

  • +21 more secondary outcomes

Study Arms (1)

PF-06840003

EXPERIMENTAL

Daily Oral PF-06840003

Drug: PF-06840003

Interventions

PF-06840003DRUG

Daily Oral PF-06840003

PF-06840003

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (14)

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095-6894, United States

Location

UCLA Clinical & Translational Research Center

Los Angeles, California, 90095, United States

Location

UCLA Oncology Center

Los Angeles, California, 90095, United States

Location

UCLA School of Medicine

Los Angeles, California, 90095, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, 87102, United States

Location

Columbia University Medical Center

New York, New York, 10019, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

CUMC Research Pharmacy

New York, New York, 10032, United States

Location

Columbia Doctors Tarrytown

Tarrytown, New York, 10591, United States

Location

Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

Duke University Medical Center, Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

Related Publications (2)

  • 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.

    PMID: 32436060DERIVED

  • 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.

    PMID: 30232146DERIVED

Related Links

MeSH Terms

Conditions

OligodendrogliomaAstrocytomaGlioma

Interventions

PF-06840003

Condition Hierarchy (Ancestors)

Neoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve Tissue

Limitations and Caveats

Part 2 of the study was not initiated. Because after reviewing efficacy, safety, PK and PD of all available data from enrolled patients, the Sponsor decided to prematurely terminate the study.

Results Point of Contact

Title
Pfizer ClinicalTrials.gov Call Center
Organization
Pfizer, Inc.
ClinicalTrials.gov_Inquiries@pfizer.com
1-800-718-1021

Study Officials

  • Pfizer CT.gov Call Center

    Pfizer

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 27, 2016

First Posted

May 6, 2016

Study Start

September 9, 2016

Primary Completion

December 26, 2018

Study Completion

December 26, 2018

Last Updated

January 27, 2020

Results First Posted

January 27, 2020

Record last verified: 2020-01

Data Sharing

IPD Sharing
Will not share

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.

Locations

US(14)