BGB-290 and Temozolomide in Treating Isocitrate Dehydrogenase (IDH)1/2-Mutant Grade I-IV Gliomas
PNOC017
A Target Validation/Phase1 Study of BGB-290 in Combination With Temozolomide in Adolescent and Young Adult IDH1/2 Newly Diagnosed and Recurrent Mutant Gliomas
3 other identifiers
interventional
78
1 country
11
Brief Summary
This phase I trial studies the side effects and best dose of BGB-290 and temozolomide in treating adolescents and young adults with IDH1/2-mutant grade I-IV glioma that is newly diagnosed or has come back. BGB-290 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving BGB-290 and temozolomide may work better in treating adolescents and young adults with IDH1/2-mutant grade I-IV glioma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Apr 2019
Longer than P75 for phase_1
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 19, 2018
CompletedFirst Posted
Study publicly available on registry
November 21, 2018
CompletedStudy Start
First participant enrolled
April 3, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 30, 2029
March 13, 2026
March 1, 2026
7.2 years
November 19, 2018
March 12, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Proportion of participants with Dose Limiting Toxicities (DLTs)
Events occurring on or after treatment on Day 1 will be classified using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Adverse events leading to treatment discontinuation will be listed.
Up to 28 days
Other Outcomes (2)
Progression free survival (PFS)
Up to 5 years
Overall survival (OS)
Up to 5 years
Study Arms (2)
Arm A (Pamiparib (BGB-290), Temozolomide (TMZ))
EXPERIMENTALParticipants with grades III-IV newly diagnosed IDH1/2 mutant glioma receive 60mg pamiparib (BGB-290) PO BID on days 1-28 and 20mg temozolomide (TMZ) PO daily on days 1-21. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
Arm B (BGB-290, Temozolomide)
EXPERIMENTALParticipants with grades I-IV recurrent IDH1/2 mutant glioma receive 60mg PARP inhibitor pamiparib (BGB-290) PO BID on days 1-28 and 20mg temozolomide PO daily on days 1-21. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Cohort B0: Participants who are surgical candidates with grades I-IV recurrent IDH1/2 mutant glioma receive 60mg PARP inhibitor BGB-290 PO BID for 7 days, pre-surgery. After recovery from surgery, participants receive PARP inhibitor BGB-290 PO BID on days 1-28 and 20mg temozolomide PO daily on days 1-21. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
Interventions
Given PO
Given PO
Eligibility Criteria
You may qualify if:
- Arm A Only: Participants must have histologically confirmed World Health Organization (WHO) grade III-IV newly diagnosed IDH1/2-mutant glioma.
- Arm B Only: WHO grades I-IV recurrent IDH1/2 mutant glioma. Participants in Arm B must have magnetic resonance imaging (MRI) confirming progressive disease; re-biopsy is encouraged, but not required at the time of recurrence for confirmation.
- Participants with a primary spinal tumor, secondary glioma, or multifocal disease in the brain, but without evidence of diffuse leptomeningeal spread, are eligible. In cases where there are questions about multifocality versus diffuse leptomeningeal spread, the study chair or co-chair must be contacted to make a final decision on eligibility.
- Participants must have IDH1 or IDH2 mutation associated with neomorphic activity of the encoded proteins.
- Participants must be willing to provide archival formalin-fixed embedded (FFPE) and frozen tissue specimens for biomarker studies if available.
- Participants in Arm A must have been treated with maximal safe resection of primary tumor followed by adjuvant radiation therapy (RT). Treatment with TMZ during radiation is allowed but not required.
- Participants in Arm B must have been treated with maximal safe resection of tumor.
- Lower grade glioma (LGG) participants who progressed after initial surgery alone are eligible. Any number of prior therapies are allowed.
- High grade glioma (HGG) participants enrolled on Arm B must have been treated with a minimum of maximal safe resection of primary tumor followed by adjuvant RT prior to recurrence. Any number of prior therapies are allowed.
- Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
- Myelosuppressive chemotherapy: participants must have received their last dose of known myelosuppressive anticancer chemotherapy at least three weeks prior to study registration or at least six weeks if nitrosourea.
- Biologic agent: participants must have recovered from any toxicity related to biologic agents and received their last dose \>= 7 days prior to study registration.
- For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval should be discussed with the study chair.
- For biologic agents that have a prolonged half-life, the appropriate interval since last treatment should be discussed with the study chair prior to registration.
- Monoclonal antibody treatment: at least three half-lives must have elapsed prior to registration, and participants on bevacizumab must have received their last dose \>= 32 days prior to study registration.
- +17 more criteria
You may not qualify if:
- Participants who are receiving any other investigational agents at any time may not be enrolled.
- Participants who have received a PARP inhibitor previously.
- Participants with active infection requiring antibiotics at time of therapy start.
- Participants with other diagnosis of malignancy.
- Participants with clinically significant active bleeding disorder, hemoptysis, or melena =\< 6 months prior to day 1.
- Participants on therapeutic anti-coagulation with heparin, warfarin, or other anticoagulants:
- Use of low-dose aspirin and/or non-steroidal anti-inflammatory agents are allowed.
- Use of thrombolytic to establish patency of indwelling venous catheters is allowed.
- Prophylactic anticoagulation for venous access devices is allowed as long as institutional normalized ratio (INR) is =\< 1.5 and partial thromboplastin time (aPTT) =\< 1.5 x institutional ULN.
- Use of low-molecular weight heparin is allowed.
- Participants with known disseminated leptomeningeal disease.
- Participants with diffuse intrinsic pontine glioma (DIPG) are not eligible for this study.
- Unresolved acute effects of any prior therapy of grade \>= 2, except for adverse events (AEs) not constituting a safety risk by investigator judgement.
- Use =\< 10 days (or =\< 5 half-lives, whichever is shorter) prior to day 1 or anticipated need for food or drugs known to be strong or moderate Cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or strong CYP3A inducers.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to TMZ or pamiparib (BGB-290).
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of California, San Franciscolead
- BeiGene USA, Inc.collaborator
Study Sites (11)
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
University of California, San Francisco
San Francisco, California, 94143, United States
Yale University
New Haven, Connecticut, 06520, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Joseph M. Sanzari Children's Hospital at Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Sabine Mueller, MD, PhD
University of California, San Francisco
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
November 19, 2018
First Posted
November 21, 2018
Study Start
April 3, 2019
Primary Completion (Estimated)
June 30, 2026
Study Completion (Estimated)
July 30, 2029
Last Updated
March 13, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL
Individual participant data after de-identification.