BGB-290 and Temozolomide in Treating Patients With Recurrent Gliomas With IDH1/2 Mutations
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ClinicalTrials.gov Identifier: NCT03914742 |
Recruitment Status :
Completed
First Posted : April 16, 2019
Last Update Posted : February 9, 2024
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Tracking Information | |||||||
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First Submitted Date ICMJE | April 11, 2019 | ||||||
First Posted Date ICMJE | April 16, 2019 | ||||||
Last Update Posted Date | February 9, 2024 | ||||||
Actual Study Start Date ICMJE | January 3, 2020 | ||||||
Actual Primary Completion Date | October 31, 2023 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Same as current | ||||||
Change History | |||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | BGB-290 and Temozolomide in Treating Patients With Recurrent Gliomas With IDH1/2 Mutations | ||||||
Official Title ICMJE | Phase I/II Study of BGB-290 With Temozolomide in Recurrent Gliomas With IDH1/2 Mutations | ||||||
Brief Summary | This phase I/II trial studies the side effects and how well BGB-290 and temozolomide work in treating patients with gliomas (brain tumors) with IDH1/2 mutations that have 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 patients with recurrent gliomas. | ||||||
Detailed Description | PRIMARY OBJECTIVES: (Phase I) I. Determine the safety and tolerability of the combination of PARP inhibitor BGB-290 (BGB-290) and temozolomide (TMZ) in patients with recurrent IDH1/2 mutant glioma, including the maximum tolerated dose (MTD) and characterization of dose-limiting toxicities (DLTs) in the Phase I portion. (Phase II) II. Determine the overall response rate of BGB-290 with TMZ in patients with recurrent IDH1/2-mutant gliomas that have progressed on TMZ and another alkylator (Arm A) in the Phase II portion. III. Determine the overall response rate of BGB-290 with TMZ in patients with recurrent IDH1/2-mutant glioma that have failed one alkylator with >= 12 months since last treatment (Arm B) in the Phase II portion. PRIMARY OBJECTIVES: I. Determine the safety and tolerability of the combination of PARP inhibitor BGB-290 (BGB-290) and temozolomide (TMZ) in patients with recurrent IDH1/2 mutant glioma, including the maximum tolerated dose (MTD) and characterization of dose-limiting toxicities (DLTs) in the Phase I portion. (Phase I) II. Determine the overall response rate of BGB-290 with TMZ in patients with recurrent IDH1/2-mutant gliomas that have progressed on TMZ and another alkylator (Arm A) in the Phase II portion. (Phase II) III. Determine the overall response rate of BGB-290 with TMZ in patients with recurrent IDH1/2-mutant glioma that have failed one alkylator with >= 12 months since last treatment (Arm B) in the Phase II portion. (Phase II) SECONDARY OBJECTIVES: I. Determine the progression-free survival (PFS) and overall survival (OS) after treatment with BGB-290 and TMZ in recurrent IDH1/2-mutant gliomas in Arms A and B. II. Determine the duration of response to therapy in recurrent IDH1/2-mutant glioma. III. Confirm the safety and tolerability of BGB-290 in combination with TMZ. EXPLORATORY OBJECTIVES: I. Assess tumor response rates, PFS, and OS in patients with World Health Organization (WHO) grade IV glioblastoma (GBM) treated with BGB-290 and TMZ. II. Assess the mutational landscape via whole-exome sequencing (WES). III. Assess gene expression patterns using ribonucleic acid (RNA) sequencing (RNAseq). IV. Assess the methylation profiling with Infinium methylation assays. V. Quantify 2-hydroxyglutarate (2HG) in archival formalin-fixed paraffin-embedded (FFPE) specimens via liquid chromatography mass spectrometry (LC-MS) detection and correlate with treatment response. VI. Correlate response with 2HG levels, somatic alterations, gene expression/methylation patterns in FFPE tumor tissue. VII. Assess tumor tissue BGB-290 levels, 2HG, and PolyADP-ribosylation (PARylation) in a patient subset treated with drug prior to re-resection. VIII. Evaluate changes in tumor growth rate in subjects with non-enhancing glioma based on fluid attenuated inverse recovery (FLAIR) tumor volume measurements of serial MRI exams. IX. Assess if change in tumor growth rate (based on FLAIR tumor volume) in subjects with non-enhancing glioma before and after treatment is associated with progression by Response Assessment in Neuro-Oncology for Low Grade Gliomas (RANO LGG; phase II patients only) or survival. OUTLINE: This is a phase I, dose de-escalation study of temozolomide followed by a phase II study. PHASE I: Patients receive PARP inhibitor BGB-290 orally (PO) twice daily (BID) on days 1-28 and temozolomide PO once daily (QD) on days 1-28, 1-21, 1-14, or 1-7. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. SURGICAL PORTION: 10 patients eligible for re-resection at the time of recurrence receive PARP inhibitor BGB-290 PO BID on days 1-6 and QD on day 7 (the morning of surgery). Within 45 days after surgery, patients receive PARP inhibitor BGB-290 PO BID on days 1-28 and temozolomide on the schedule established in Phase I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. PHASE II: Patients receive PARP inhibitor BGB-290 PO BID on days 1-28 and temozolomide PO QD on the schedule established in Phase I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days, every 2 months for 2 years, then every 6 months thereafter. |
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Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 1 Phase 2 |
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Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Single Group Assignment Intervention Model Description: Phase 1: BGB-290 in combination with TMZ in patients w/ IDH1/2-mutant WHO grade II-IV recurrent glioma: Phase 2: Grade II-III patients in will be stratified into 2 arms based on the timing of prior alkylator chemotherapy exposure; a third arm will include the subset of glioblastoma (grade IV) patients 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 | Completed | ||||||
Actual Enrollment ICMJE |
60 | ||||||
Original Estimated Enrollment ICMJE |
100 | ||||||
Actual Study Completion Date ICMJE | October 31, 2023 | ||||||
Actual Primary Completion Date | October 31, 2023 (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 | 18 Years and older (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
Listed Location Countries ICMJE | United States | ||||||
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Administrative Information | |||||||
NCT Number ICMJE | NCT03914742 | ||||||
Other Study ID Numbers ICMJE | ABTC-1801 UM1CA137443 ( U.S. NIH Grant/Contract ) |
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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 | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | ||||||
Original Responsible Party | Same as current | ||||||
Current Study Sponsor ICMJE | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | ||||||
Original Study Sponsor ICMJE | Same as current | ||||||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | ||||||
Verification Date | February 2024 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |