What side effects are associated with this type of intervention?

The most common treatments for gliomas, such as BGB-290 (enzyme inhibition) and temozolomide (chemotherapy), have distinct side effects. BGB-290 may cause fatigue, nausea, and liver enzyme abnormalities. Temozolomide is associated with nausea, vomiting, fatigue, and myelosuppression. Both treatments require careful management of these side effects to ensure patient safety and treatment efficacy.

What prior FDA approvals exist?

The FDA has approved several treatments for gliomas, focusing on both enzyme inhibition and chemotherapy. Temozolomide, an oral alkylating agent, is a cornerstone in the treatment of high-grade gliomas, particularly glioblastoma multiforme. It works by damaging the DNA of cancer cells, thereby inhibiting their ability to replicate. Enzyme inhibitors like BGB-290, which target specific enzymes necessary for tumor growth, are also being explored. While BGB-290 itself is still under investigation, other enzyme inhibitors such as bevacizumab, which targets vascular endothelial growth factor (VEGF), have been approved for recurrent glioblastoma. These treatments aim to halt tumor progression by interfering with the molecular pathways essential for cancer cell survival and proliferation.

What other types of research exist?

Promising novel alternatives for glioma treatment in 2024 include: 1) Immunotherapy agents such as checkpoint inhibitors (e.g., pembrolizumab, nivolumab) which enhance the immune system's ability to target cancer cells. 2) CAR-T cell therapy, which involves modifying a patient's T cells to better recognize and attack glioma cells. 3) Targeted therapies like FGFR inhibitors (e.g., infigratinib) for tumors with specific genetic alterations. 4) Novel anti-angiogenic agents that inhibit tumor blood vessel formation. These alternatives are currently being explored in clinical trials and may offer new hope for glioma patients.

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PARP Inhibitor

PARP Inhibitor + Temozolomide for Brain Cancer (PNOC017 Trial)

Phase 1

Recruiting

Led By Sabine Mueller

Research Sponsored by University of California, San Francisco

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Subjects in Arm B must have been treated with maximal safe resection of tumor.

Monoclonal antibody treatment: at least three half-lives must have elapsed prior to registration, and subjects on bevacizumab must have received their last dose >= 32 days prior to study registration.

Must not have

Subjects with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.

Subjects with diffuse intrinsic pontine glioma (DIPG) are not eligible for this study.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial studies the safety and best dose of BGB-290 and temozolomide in treating young people with a specific type of brain tumor. BGB-290 blocks enzymes needed for tumor growth, while temozolomide kills or stops cancer cells from growing. The goal is to find out if this combination works better for these patients.

Who is the study for?

Adolescents and young adults with newly diagnosed or recurrent IDH1/2-mutant grade I-IV glioma. Participants must have stable neurological deficits, not be on certain medications, have specific blood counts and organ functions within normal ranges, be able to swallow capsules, agree to use contraception if of childbearing potential, and provide tissue samples for study. Exclusions include prior treatment with IDH inhibitors, active infections or other cancers, bleeding disorders within the last 6 months, unresolved effects from previous therapies that pose a safety risk.

What is being tested?

The trial is testing the combination of BGB-290 (a PARP inhibitor) and Temozolomide (a chemotherapy drug) in treating brain tumors with specific genetic mutations. The goal is to determine the safest doses while assessing how well these drugs work together to inhibit tumor growth by blocking enzymes needed for cell growth and killing or stopping cancer cells from dividing.

What are the potential side effects?

Potential side effects may include typical reactions associated with chemotherapy such as nausea, fatigue, hair loss; as well as those related to BGB-290 like anemia or low white blood cell counts which can increase infection risk. There might also be liver function changes due to medication interactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have had surgery to remove as much of my tumor as safely possible.

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It has been long enough since my last monoclonal antibody treatment to join this study.

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My kidney function, measured by creatinine levels, is within the normal range.

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I had my last dose of strong chemotherapy 3 weeks ago, or 6 weeks ago if it was a specific type (nitrosourea).

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My cancer has a specific genetic change in IDH1 or IDH2.

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I am over 16 and can do most activities, or I am 16 or under and can do most activities for my age.

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My platelet count is at least 100,000/mm^3 without transfusions for 7 days.

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I can swallow capsules.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I can attend all required follow-up visits and tests.

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I do not have diffuse intrinsic pontine glioma.

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My cancer has spread to the lining of my brain and spinal cord.

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I am not on antibiotics for an infection when starting therapy.

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I have previously been treated with a PARP inhibitor.

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I have not been treated with IDH1 or IDH2 inhibitors or any investigational drugs.

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I have been diagnosed with another type of cancer.

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I am not HIV-positive or on antiretroviral therapy.

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I do not have any serious illnesses that would stop me from following the study's requirements.

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I am currently taking blood thinners like heparin or warfarin.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Proportion of participants with Dose Limiting Toxicities (DLTs)

Other study objectives

Overall survival (OS)

Progression free survival (PFS)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm B (BGB-290, temozolomide)Experimental Treatment2 Interventions

Patients with grades I-IV recurrent IDH1/2 mutant glioma receive 60mg PARP inhibitor BGB-290 PO BID on days 1-28 and 20mg 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: Patients who are surgical candidates with grades I-IV recurrent IDH1/2 mutant glioma receive 60mg PARP inhibitor BGB-290 PO BID for 7 days, pre-surgery. After recovery from surgery, patients receive PARP inhibitor BGB-290 PO BID on days 1-28 and 20mg 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.

Group II: Arm A (BGB-290, temozolomide)Experimental Treatment2 Interventions

Patients with grades III-IV newly diagnosed IDH1/2 mutant glioma receive 60mg PARP inhibitor BGB-290 PO BID on days 1-28 and 20mg 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

PARP Inhibitor BGB-290

2020

Completed Phase 2

~60

Temozolomide

2010

Completed Phase 3

~1880

0 / 18Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

BGB-290, a PARP inhibitor, works by blocking enzymes crucial for DNA repair, causing cancer cells to accumulate DNA damage and die. Temozolomide, an alkylating chemotherapy agent, damages DNA directly, preventing tumor cells from dividing. For glioma patients, these mechanisms are significant because gliomas are highly aggressive and often resistant to treatment. By combining BGB-290 with Temozolomide, the treatment can potentially enhance the DNA damage in tumor cells, improving the effectiveness of therapy and offering a better chance at controlling tumor growth and prolonging survival.