This phase I trial studies the side effects of GDC-0084 and radiation therapy to the brain in treating patients with PI3K pathway-mutated solid tumors that have spread to the brain and/or membranes lining the brain and spinal cord (brain and/or leptomeninges metastases). When a cancer has a PI3K pathway mutation, it sends signals to other cells in the body to encourage rapid growth, leading to the spread of cancer. PI3K mutations are common in many types of cancer, and they cause radiation therapy to be less effective. GDC-0084 reduces the activity of PI3K-related signaling. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving GDC-0084 with whole or partial brain radiation therapy may be an effective treatment for solid tumors brain metastases or leptomeningeal metastases.
Additional locations may be listed on ClinicalTrials.gov for NCT04192981.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVE:
I. To determine the safety and toxicity of concurrent paxalisib (GDC-0084) and radiation therapy to the brain in patients with solid tumor brain metastases and/or leptomeningeal metastases harboring PI3K pathway mutations.
SECONDARY OBJECTIVES:
I. To determine the local recurrence rate of brain metastases or leptomeningeal metastases treated with concurrent GDC-0084 and radiation therapy to the brain in patients with solid tumor brain metastases harboring PI3K pathway mutations.
II. To determine the intracranial progression-free survival and overall survival in patients with solid tumor brain metastases harboring PI3K pathway mutations.
III. To further assess the safety and toxicity of protocol therapy in the dose expansion cohort.
OUTLINE: This is a dose escalation study of GDC-0084.
Patients receive GDC-0084 orally (PO) once daily (QD) on days 1-21, and undergo undergo whole brain radiation therapy (WBRT) or partial radiation brain therapy (PBRT) for 10 fractions over approximately 2 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 1, 3, 6, 9,and 12 months, and then every 3 months thereafter.
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorBrandon Imber
