What side effects are associated with this type of intervention?

Common treatments for brain tumors, particularly those involving PI3K/mTOR inhibitors like GDC-0084, often include chemotherapy, radiation therapy, and targeted therapies. Known side effects of these treatments can include fatigue, nausea, vomiting, headache, and increased risk of infection due to immunosuppression. Specific to PI3K/mTOR inhibitors, side effects may also include hyperglycemia, mucositis, rash, and gastrointestinal disturbances. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for brain tumors, including targeted therapies and chemotherapeutic agents. While specific FDA approvals for PI3K/mTOR inhibitors like GDC-0084 are not detailed in the provided context, other related drugs such as everolimus, an mTOR inhibitor, have shown efficacy in treating various cancers, including brain tumors. Additionally, investigational therapies like ONC201 and DNX-2401 are being actively studied for their potential in treating diffuse intrinsic pontine glioma and other high-grade gliomas.

What other types of research exist?

Promising novel alternatives to GDC-0084 for brain tumor patients include: 1) Bevacizumab, an anti-VEGF antibody, which has shown efficacy in various brain tumors including gliomas and meningiomas. 2) ONC201, a selective DRD2 antagonist, which has demonstrated activity in H3 K27M-mutant diffuse midline gliomas. 3) Ivosidenib, a mutant-IDH1 inhibitor, which has shown promise in IDH1-mutant gliomas. 4) Everolimus, an mTORC1 inhibitor, which has been effective in combination therapies for meningiomas and other brain tumors. 5) Dual mutant-IDH1/2 inhibitor Vorasidenib, currently in phase III trials for IDH1/2-mutant gliomas.

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PI3K Inhibitor

GDC-0084 + Radiation for Brain Cancer

Phase 1

Waitlist Available

Led By T. Jonathan Yang, MD, PhD

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

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

Must have

KPS ≥ 70

Adequate bone marrow function

Must not have

Known hypersensitivity or intolerance to GDC-0084 or to any other inhibitor of the PI3K/ Akt/ mTOR pathway

Previous radiotherapy to the intended treatment site that precludes developing a treatment plan that respects tissue tolerances

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug, GDC-0084, combined with radiation therapy for people whose brain cancer has a specific genetic mutation. The goal is to find the safest dose and see if this combination treatment works better against their cancer.

Who is the study for?

This trial is for adults with solid tumor brain metastases or leptomeningeal metastases, specifically those with a PIK3CA mutation. Participants must be over 18, able to consent, have good performance status (KPS ≥ 70), and can swallow pills. They should not have had recent systemic therapy and must use effective contraception if of reproductive potential.

What is being tested?

The study is testing the safety and effectiveness of GDC-0084 when combined with whole brain radiation therapy in treating cancer that has spread to the brain. It aims to determine the highest dose of GDC-0084 that causes few or mild side effects.

What are the potential side effects?

Potential side effects may include issues related to organ inflammation such as interstitial lung disease, problems from drug interactions affecting metabolism, heart rhythm abnormalities (QT interval prolongation), and general intolerance or allergic reactions to components of GDC-0084.

Eligibility Criteria

Inclusion Criteria

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

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I am mostly able to care for myself.

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My bone marrow is working well.

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My seizures caused by brain cancer are under control with medication.

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I can swallow and keep down pills.

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My cancer has spread to my brain, confirmed by an MRI.

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I am 18 years old or older.

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My cancer has a PIK3CA mutation.

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I take less than 4mg of dexamethasone daily.

Exclusion Criteria

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

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I am allergic or have had a bad reaction to GDC-0084 or similar medications.

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I've had radiation before where they now want to treat, and can't have more without risking harm.

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I have health conditions that prevent me from receiving radiation therapy.

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I have had lung conditions that needed steroid treatment.

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I am not taking drugs that strongly affect how my body processes certain medications.

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I have heart problems.

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I am eligible for a specific type of brain radiation therapy.

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I take insulin for my diabetes.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 year for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

maximum tolerated dose (MTD)

Secondary study objectives

local recurrence rate

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Concurrent GDC-0084 with RadiationExperimental Treatment2 Interventions

GDC-0084 in 3 + 3 dose-escalation in 3 cohorts: 45, 60, 75 mg daily, with a potential de-escalation cohort to 30mg, to determine MTD in combination with whole brain radiation therapy radiation therapy to 30Gy in 10 fractions. Once MTD is determined, 12 additional patients will be treated with GDC-0084 at MTD in combination with whole brain radiation therapy.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

GDC-0084

Not yet FDA approved

0 / 16Eligibility 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

Common treatments for brain tumors include PI3K/mTOR inhibitors like GDC-0084, which target the PI3K/mTOR pathway involved in cell growth and survival, thereby inhibiting tumor progression. Temozolomide, an alkylating agent, works by damaging the DNA of cancer cells, leading to cell death. Bevacizumab, an anti-angiogenic drug, inhibits the formation of new blood vessels that tumors need to grow. These treatments are crucial for brain tumor patients as they target specific pathways and mechanisms essential for tumor growth and survival, potentially improving outcomes and providing more personalized therapeutic options.

Bioinformatics analysis reveals potential candidate drugs for different subtypes of glioma.