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.
PRIMARY OBJECTIVES: I. Determine the safety and tolerability of the combination of Poly (ADP-Ribose) polymerase (PARP) inhibitor BGB-290 (BGB-290) and temozolomide (TMZ) in adolescent and young adult (AYA) subjects with IDH1/2-mutant glioma, including the maximum tolerated dose (MTD) and characterization of dose-limiting toxicities (DLTs) in both, newly diagnosed and recurrent treatment arms. With the completion of ABTC1801, a Phase I/II Study of BGB-290 with Temozolomide in Recurrent Gliomas with IDH1/2 Mutations, a maximum tolerated dose (MTD) for adults has been found. This study will advance to evaluate preliminary efficacy using this dose in patients 13-25 years of age. EXPLORATORY OBJECTIVES: I. Evaluate the preliminary efficacy of BGB-290 and temozolomide in terms of progression free survival (PFS) and overall survival (OS) in Arm A and B stratified by tumor diagnosis, calculated using the Kaplan-Meier method with a goal of improving the historical high grade glioma progression free survival of 10% and overall survival of 20% at 2 years. II. Assess the mutational landscape studies via whole-exome sequencing (WES). III. Assessment of gene expression patterns using ribonucleic acid (RNA) sequencing (RNAseq). IV. Assess the methylation profiling with Infinium methylation assays. V. Assess the oncometabolite profiling via liquid chromatography (LC)/mass spectrometry (MS)-MS. VI. Assess the intratumoral drug level assessments via LC/MS-MS. VII. To assess Quality of Life (QOL) and cognitive measures in adolescent and young adult patients with newly diagnosed and recurrent mutant gliomas. VIII. To assess patient and/or proxy satisfaction with study participation via patient-reported outcome (PRO) measures in the context of race ethnicity and other health related social risks. IX. To assess on therapy toxicity in the context of race, ethnicity and other health related social risks. OUTLINE: Participants are assigned to 1 of 2 cohorts. The dose escalation component of the trial has been completed, which included patients ages 13-17 and the study will proceed with enrolling patients ages 13-25 years old onto the expansion cohort and target validation component at the ABTC pre-determined dose. Arm A: Newly diagnosed IDH1/2-mutant high-grade glioma patients receive PARP inhibitor BGB-290 orally (PO) twice daily (BID) on days 1-28 and 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. Arm B: Recurrent IDH1/2-mutant low-grade or high-grade glioma patients receive PARP inhibitor BGB-290 orally (PO) twice daily (BID) on days 1-28 and 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: Recurrent IDH1/2-mutant low-grade or high-grade glioma patients receive PARP inhibitor BGB-290 PO for 7 days pre-surgery at the ABTC-determined MTD. After recovery from surgery (14-28 days), the patient will proceed to the efficacy component of the trial. After completion of study treatment, patients are followed up for 5 years. If participants are co-enrolled on the PNOC COMP protocol, participants will be followed under the PNOC COMP protocol until death or withdrawal from study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
78
Given PO
Given PO
Children's Hospital Los Angeles
Los Angeles, California, United States
University of California, San Francisco
San Francisco, California, United States
Yale University
New Haven, Connecticut, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Washington University School of Medicine
St Louis, Missouri, United States
Joseph M. Sanzari Children's Hospital at Hackensack University Medical Center
Hackensack, New Jersey, United States
Duke University Medical Center
Durham, North Carolina, United States
Oregon Health and Science University
Portland, Oregon, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
...and 1 more locations
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.
Time frame: Up to 28 days
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