BGB-290 and Temozolomide in Treating Isocitrate Dehydrogenase (IDH)1/2-Mutant Grade I-IV Gliomas

Titre officiel

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

Sommaire:

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 tumour 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 tumour 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.

Description de l'essai

Primary Outcome:

• Summary of Dose Limiting Toxicities Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0

PRIMARY OBJECTIVES:

• 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.

EXPLORATORY OBJECTIVES:

• 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 tumour 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.
• Assess the mutational landscape studies via whole-exome sequencing (WES).
• Assessment of gene expression patterns using ribonucleic acid (RNA) sequencing (RNAseq).
• Assess the methylation profiling with Infinium methylation assays.
• Assess the oncometabolite profiling via liquid chromatography (LC)/mass spectrometry (MS)-MS.
• Assess the intratumoural drug level assessments via LC/MS-MS.

OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 cohorts. After the MTD is established, additional patients will be enrolled into the efficacy component of the trial. 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 MTD determined in the Phase I portion. 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.

Voir cet essai sur ClinicalTrials.gov