GDC-0084 + Radiation for Brain Cancer

Not currently recruiting at 11 trial locations

Overseen By Brandon Imber, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Enzyme inducers/inhibitors

Disqualifiers: Insulin-treated diabetes, Cardiac dysfunction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 10

Duration: 10 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if GDC-0084, a new potential drug, combined with radiation therapy, is safe and effective for treating brain cancer that has spread from other parts of the body. The focus is on individuals whose cancer has a specific genetic change called a PIK3CA mutation. Researchers will test different doses of GDC-0084 to identify the highest dose that remains safe with only mild side effects. This trial may suit those with solid tumor brain metastases who can manage their daily life with this condition. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that you cannot take medications that affect the metabolism of GDC-0084. If you are on such medications, you may need to stop or adjust them.

Is there any evidence suggesting that GDC-0084 in combination with radiation therapy is likely to be safe for humans?

Research has shown that GDC-0084, a drug designed to target certain cancer pathways, may help treat cancer that has spread to the brain. It effectively reaches the brain, indicating its potential as a treatment.

Since this trial is in its early stages, the main goal is to test the drug's safety when used with radiation therapy. Researchers aim to find the highest dose that causes only mild or few side effects. Previous studies have tested GDC-0084 alone and with other treatments, suggesting it could be safe. However, more research is needed to confirm this.

In summary, while early results are promising, this trial focuses on assessing the drug's safety in humans, especially when combined with radiation. Participants will help researchers understand how well people tolerate GDC-0084, which could lead to future treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for brain cancer, which often include surgery, chemotherapy, and radiation, GDC-0084 targets a specific pathway in cancer cells, known as the PI3K pathway. This pathway plays a crucial role in cancer cell growth and survival, making GDC-0084 potentially more effective at halting tumor progression. Researchers are excited because GDC-0084 is designed to work in conjunction with radiation therapy, which may enhance its overall impact by making cancer cells more sensitive to radiation. This combination could offer a more powerful approach to treating brain cancer than current options.

What evidence suggests that the combination of GDC-0084 and radiation might be an effective treatment for brain cancer?

Studies have shown that GDC-0084 can enter the brain and target a pathway often involved in cancer growth. Research indicates that this drug significantly slows tumor growth, achieving a 70% reduction in certain brain cancer models. In this trial, participants will receive a combination of GDC-0084 and whole brain radiation therapy. Early findings suggest that this combination might effectively treat cancer that has spread to the brain and could potentially improve outcomes for patients with specific cancer mutations. ^{1 2 6 7 8}

Who Is on the Research Team?

Brandon Imber, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

Patient at reproductive potential must agree to practice an effective contraceptive method

My kidneys are working well.

My liver is working well.

Exclusion Criteria

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

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

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive GDC-0084 in combination with radiation therapy to determine the maximum tolerated dose

10 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• GDC-0084
• Whole Brain Radiation Therapy

Trial Overview 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.

How Is the Trial Designed?

Group I: Concurrent GDC-0084 with Radiation Experimental Treatment 2 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.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Kazia Therapeutics

Collaborator

Trials

1

Recruited

20+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6685218/

The dual PI3K/mTOR-pathway inhibitor GDC-0084 ... The results of this study suggest that the brain-penetrant PI3K/mTOR-targeting GDC-0084 is a promising treatment option for breast cancer brain metastases with ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30796030/

The Dual PI3K/mTOR Pathway Inhibitor GDC-0084 Achieves ... The results of this study suggest that the brain-penetrant PI3K/mTOR targeting GDC-0084 is a promising treatment option for breast cancer ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0090955624099550

Brain Distribution and Efficacy of the Brain Penetrant PI3K ... GDC-0084 achieved significant tumor growth inhibition of 70% and 40% against the U87 and GS2 orthotopic models, respectively. GDC-0084 distribution throughout ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04192981

NCT04192981 | GDC-0084 With Radiation Therapy for ... This study will test the safety of the study drug, GDC-0084, in combination with radiation therapy in people who have solid tumor brain metastases or ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2019-08530

GDC-0084 and Radiation Therapy for the Treatment of ... Giving GDC-0084 with whole or partial brain radiation therapy may be an effective treatment for solid tumors brain metastases or leptomeningeal metastases.

6. aacrjournals.org aacrjournals.org/cancerres/article/80/4_Supplement/OT1-08-05/646114/Abstract-OT1-08-05-Phase-II-trial-of-GDC-0084-in

Abstract OT1-08-05: Phase II trial of GDC-0084 in combination ... Secondary endpoints include overall survival, safety and patient-reported outcomes.

7. trials.braintumor.org trials.braintumor.org/trials/NCT04192981

GDC-0084 With Radiation Therapy for People With PIK3CA ... This study will test the safety of the study drug, GDC-0084, in combination with radiation therapy in people who have solid tumor brain metastases or ...

8. pubs.acs.org pubs.acs.org/doi/10.1021/acsmedchemlett.6b00005

Discovery of Clinical Development Candidate GDC-0084, a ... Despite the evident free brain penetration of 1 and 2, they were not selected for clinical development due to poor projected clearance in humans ...