BGB-290 and Temozolomide in Treating Isocitrate Dehydrogenase (IDH)1/2-Mutant Grade I-IV Gliomas (PNOC017)
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ClinicalTrials.gov Identifier: NCT03749187 |
Recruitment Status :
Recruiting
First Posted : November 21, 2018
Last Update Posted : February 23, 2024
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Tracking Information | |||||||
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First Submitted Date ICMJE | November 19, 2018 | ||||||
First Posted Date ICMJE | November 21, 2018 | ||||||
Last Update Posted Date | February 23, 2024 | ||||||
Actual Study Start Date ICMJE | April 3, 2019 | ||||||
Estimated Primary Completion Date | June 30, 2024 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
Proportion of participants with Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 28 days ] 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.
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Original Primary Outcome Measures ICMJE |
Summary of Dose Limiting Toxicities Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 [ Time Frame: Up to 28 days ] Events occurring on or after treatment on Day 1 will be summarized by mapped term, appropriate thesaurus level, and CTCAE v5.0 grade. Adverse events leading to treatment discontinuation will be listed.
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Change History | |||||||
Current Secondary Outcome Measures ICMJE | Not Provided | ||||||
Original Secondary Outcome Measures ICMJE | Not Provided | ||||||
Current Other Pre-specified Outcome Measures |
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Original Other Pre-specified Outcome Measures |
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Descriptive Information | |||||||
Brief Title ICMJE | BGB-290 and Temozolomide in Treating Isocitrate Dehydrogenase (IDH)1/2-Mutant Grade I-IV Gliomas | ||||||
Official Title ICMJE | 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 | ||||||
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. | ||||||
Detailed Description | 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. 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. |
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Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 1 | ||||||
Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Recruiting | ||||||
Estimated Enrollment ICMJE |
78 | ||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||
Estimated Study Completion Date ICMJE | July 30, 2029 | ||||||
Estimated Primary Completion Date | June 30, 2024 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 13 Years to 25 Years (Child, Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | United States | ||||||
Removed Location Countries | Canada | ||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT03749187 | ||||||
Other Study ID Numbers ICMJE | 18083 NCI-2018-02345 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) PNOC017 ( Other Identifier: Pacific Pediatric Neuro-Oncology Consortium ) |
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Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | Sabine Mueller, MD, PhD, University of California, San Francisco | ||||||
Original Responsible Party | Same as current | ||||||
Current Study Sponsor ICMJE | University of California, San Francisco | ||||||
Original Study Sponsor ICMJE | Same as current | ||||||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | University of California, San Francisco | ||||||
Verification Date | February 2024 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |