GDC-0084 With Radiation Therapy for People With PIK3CA-Mutated Solid Tumor Brain Metastases or Leptomeningeal Metastases

Inclusion Criteria:

* Histologically confirmed solid tumor malignancies harboring PIK3CA mutations which include mutations in any of the following genes: PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3C2G, PIK3C3, INPP4A, INPP4B, INPPL1, INPP5D, PTEN, AKT1, AKT2, AKT3, and MTOR.
* Brain metastases and/or leptomeningeal metastases involving the brain demonstrated by MR imaging of the brain. For patients with brain metastases, measurable lesion by RANO-BM is required28. Patients with spine leptomeningeal metastases are eligible for the study if they have leptomeningeal metastases of the brain demonstrated by MRI imaging of the brain.
* KPS ≥ 70
* Age ≥ 18 years
* Able to provide informed consent.
* If a patient is on corticosteroid, he/she must be on a stable daily dose of \< 4mg dexamethasone or equivalent. Patient does not need to be given corticosteroid as prophylaxis if not clinically indicated.
* No limit to prior therapies with the last systemic therapy ≥ 1 week from initiation of protocol therapy. Systemic therapy can resume after completion of protocol DLT assessment period.
* Patients with prior SRS are eligible, provided that there are new, non-irradiated brain lesions or leptomeningeal metastases. Patients must be ≥ 3 months post prior cranial radiation therapy.
* Patients with seizure history related to brain metastases or leptomeningeal metastases controlled on antiepileptic medications are eligible.
* Patient at reproductive potential must agree to practice an effective contraceptive method
* Patient must be able to swallow and retain oral medication
* Adequate organ function as assessed by laboratory tests.
* Adequate bone marrow function

  * Hemoglobin ≥ 8g/dL
  * Absolute neutrophil count ≥1,000/mm\^3
  * Platelet count ≥ 100,000/mm\^3
* Adequate liver function

  * Bilirubin ≤1.5 times upper limit normal (ULN)
  * AST and ALT ≤ 2.5 times ULN
  * Alkaline phosphatase ≤ 2 times ULN
* Adequate renal function ° BUN and Creatinine ≤ 1.5 times ULN

Exclusion Criteria:

* Previous radiotherapy to the intended treatment site that precludes developing a treatment plan that respects tissue tolerances
* Patients with brain metastases eligible for single fraction stereotactic radiation therapy
* Serious medical co-morbidities precluding radiotherapy
* Insulin-treated diabetes; subjects with diabetes or impaired glucose tolerance that is not treated with insulin may be enrolled
* QT interval ≥ 450 msec on EKG
* Cardiac dysfunction defined as: myocardial infarction within 6 months of study entry, NYHA Class II/III/IV heart failure, unstable angina or unstable cardiac arrhythmias
* Known hypersensitivity or intolerance to GDC-0084 or to any other inhibitor of the PI3K/ Akt/ mTOR pathway
* Past medical history of interstitial lung disease, drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active interstitial lung disease
* Subject receiving any medications or substances that are moderate and/or potent enzyme inducers or inhibitors which may have an effect on the metabolism of GDC-0084.
* Pregnant or lactating women.