BGB-290 and Temozolomide in Treating Patients With Recurrent Gliomas With IDH1/2 Mutations

Recruiting in Palo Alto (17 mi)

+12 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

No Placebo Group

Trial Summary

What is the purpose of this trial?

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.

Eligibility Criteria

Inclusion Criteria

- Recurrence in non-enhancing tumors will be defined as 25% or more increase in bi-dimensional product of FLAIR signal abnormality (measurable disease) per the low-grade glioma (LGG) RANO criteria. Contrast-enhancing tumors with measurable enhancing targets will be defined as recurrent based on standard RANO criteria.

Patients must have documented molecular 1p/19q and MGMT testing. If either of these studies has not been performed previously, they can be done prior to enrollment.

- 6 weeks from a nitrosourea chemotherapy

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Exclusion Criteria

Patients who have received bevacizumab within the last 6 months are ineligible.

Patients with a known hypersensitivity to TMZ are ineligible.

Patients who have received a PARP inhibitor previously are excluded.

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Treatment Details

Interventions

BGB-290 (PARP Inhibitor)
Temozolomide (Alkylating agents)
Therapeutic Conventional Surgery (Procedure)

Participant Groups

5Treatment groups

Experimental Treatment

Group I: Surgical ArmExperimental Treatment3 Interventions

Recurrent IDH1/2-mutant glioma (WHO grade II-IV) eligible for re-resection BGB-290: 60mg PO BID for 6 days AND day once day of surgery (day 7)

Group II: Phase 2: Arm B NOT Alkylator-resistantExperimental Treatment2 Interventions

Grade II-III:Recurrent IDH1/2-mutant glioma (WHO grades II/III) Failed TMZ OR another alkylator; \>/=12 months since last treatment BGB290 + TMZ at dose combination established in Phase 1

Group III: Phase 2: Arm A Alkylator-resistantExperimental Treatment2 Interventions

Grade II-III: Recurrent IDH1/2-mutant glioma (WHO grades II/III) who have failed TMZ AND another alkylator BGB290 + TMZ at dose combination established in Phase 1

Group IV: Phase 1: Dose FindingExperimental Treatment2 Interventions

Recurrent IDH1/2-mutant grade II-III glioma: BGB290: Days 1-28, 60 mg PO BID TMZ: Days 1-28, 20 QD starting dose TMZ de-escalated treatment schedule if necessary (days 1-21; days 1-14; days 1-7) BGG held constant at 60mg PO BID

Group V: GBM ArmExperimental Treatment2 Interventions

Exploratory grade IV patients only BGB290 at Ph II dose for 7 days pre-surgery Progressed following RT + Chemo