Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)

Inclusion Criteria:

Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol
Patients must have an AKT mutation as determined via the MATCH Master Protocol

Patients with hormone receptor positive, defined as estrogen receptor and/or progesterone receptor > 1% by immunohistochemistry, AND HER2 negative unresectable breast cancer, with no overexpression by immunohistochemistry (IHC) or amplification by in-situ hybridization, are allowed to continue fulvestrant or an aromatase inhibitor (anastrozole, letrozole, exemestane) with AZD5363 if patient just progressed on this anti-estrogen therapy. Gonadotrophin releasing hormone (GnRH) agonists (such as leuprolide or goserelin) are allowed. For instance, if the last treatment was letrozole plus goserelin, the patient is allowed to continue the letrozole plus goserelin with AZD5363

NOTE: Selective estrogen receptor modulators (SERMs), such as tamoxifen or toremifene, are not allowed, given concerns about CYPD26 and CYP3A4 metabolism, respectively
Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)

Patients with diabetes or risk for hyperglycemia are eligible. Patients with diabetes mellitus may enter the study unless any of the following exclusion criteria are fulfilled:

Baseline fasting glucose value of > 8.9 mmol/L or 160 mg/dL (fasting is defined as no calorific intake for at least 8 hours)
Insulin required for routine diabetic management and control
More than two oral hypoglycemic medications required for routine diabetic management and control

Exclusion Criteria:

Patients must not have known hypersensitivity to AZD5363 or compounds of similar chemical or biologic composition
Patients with known KRAS, NRAS, HRAS, or BRAF mutations are not eligible for this protocol, as these mutations may lead to limited response due to resistance
Patients may not have received treatment with another inhibitor of PI3K, AKT or mTOR in the neoadjuvant, adjuvant or metastatic setting with the exception of FDA approved rapalogs. Patients with metastatic cancer, who received PI3K/AKT/mTOR inhibitors on short preoperative window trials (treatment for 4 weeks or less) will be eligible if the treatment was over 6 months prior to registration
Patients may not have received strong inhibitors or potent inducers or substrates of CYP3A4 or substrates of CYP2D6 within 2 weeks before the first dose of study treatment (3 weeks for St John's Wort)