GDC-0084 + Radiation for Brain Cancer

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

21 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the treatment GDC-0084 + Whole Brain Radiation Therapy for brain cancer?

Research shows that whole brain radiation therapy can provide rapid neurological improvement and palliative benefits for patients with brain metastases, often maintaining these effects throughout the patient's life. Although the benefits of radiotherapy for highly malignant gliomas are modest, it is more effective than chemotherapy and can extend survival by several weeks to months. ^{1 2 3 4 5}

Is GDC-0084 safe for use in humans?

GDC-0084 has been tested in a phase I study with patients who have high-grade glioma, which is a type of brain cancer. This study is an early step in understanding its safety, and while it shows that GDC-0084 can reach the brain and affect cancer cells, more research is needed to fully understand its safety profile. ^{2 6 7 8 9}

How does the drug GDC-0084 differ from other treatments for brain cancer?

GDC-0084 is unique because it is a targeted therapy that inhibits the PI3K pathway, which is often overactive in brain cancer cells, potentially making it more effective when combined with radiation therapy compared to traditional treatments that do not specifically target this pathway. ^{10 11 12 13 14}

Research Team

Brandon Imber, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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.

I finished my last cancer treatment more than a week ago.

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

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

Treatment Details

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.

Participant Groups

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+

References

1. United States pubmed.ncbi.nlm.nih.gov

Utility of apparent diffusion coefficient in predicting the outcome of Gamma Knife-treated brain metastases prior to changes in tumor volume: a preliminary study. [2008]

2. France pubmed.ncbi.nlm.nih.gov

Radiation-enhancing effect of sodium glycididazole in patients suffering from non-small cell lung cancer with multiple brain metastases: A randomized, placebo-controlled study. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Stereotactic radiotherapy of appropriately selected meningiomas and metastatic brain tumor beds with gamma knife icon versus volumetric modulated arc therapy. [2021]

4. Korea (South) pubmed.ncbi.nlm.nih.gov

Efficacy of Gamma Knife Radiosurgery for Recurrent High-Grade Gliomas with Limited Tumor Volume. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Brain tumors. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

First-in-Human Phase I Study to Evaluate the Brain-Penetrant PI3K/mTOR Inhibitor GDC-0084 in Patients with Progressive or Recurrent High-Grade Glioma. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Multiparametric MR-PET Imaging Predicts Pharmacokinetics and Clinical Response to GDC-0084 in Patients with Recurrent High-Grade Glioma. [2021]

8. England pubmed.ncbi.nlm.nih.gov

An LC/ESI-MS/MS method to quantify the PI3K inhibitor GDC-0084 in human plasma and cerebrospinal fluid: Validation and clinical application. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Brain Distribution and Efficacy of the Brain Penetrant PI3K Inhibitor GDC-0084 in Orthotopic Mouse Models of Human Glioblastoma. [2019]

10. France pubmed.ncbi.nlm.nih.gov

[Radiotherapy of glioblastoma]. [2019]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Radiation-Induced Changes in Tumor Vessels and Microenvironment Contribute to Therapeutic Resistance in Glioblastoma. [2020]

12. United States pubmed.ncbi.nlm.nih.gov

Large dose fraction radiotherapy in the treatment of glioblastoma. [2019]

13. United States pubmed.ncbi.nlm.nih.gov

Accelerated Hypofractionated Radiotherapy in the Era of Concurrent Temozolomide Chemotherapy in Elderly Patients with Glioblastoma Multiforme. [2020]

14. United States pubmed.ncbi.nlm.nih.gov

Response to chemotherapy of a radiation-induced glioblastoma multiforme. [2018]