Clinical Trial Finder

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)

PRIMARY OBJECTIVE:

• I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.

SECONDARY OBJECTIVES:

• I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.

• II. To evaluate time until death or disease progression.

• III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.

• IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens.

OUTLINE: Patients receive capivasertib (AZD5363) orally (PO) twice daily (BID) on days 1-4, 8-11, 15-18, and 22-25. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months if less than 2 years from study entry, and then every 6 months for year 3 from study entry.

Arms

Experimental: Treatment (capivasertib)

Patients receive capivasertib PO BID on days 1-4, 8-11, 15-18, and 22-25. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Interventions

Drug: - Capivasertib

Given PO