This phase II MATCH treatment trial tests how well ipatasertib works in treating patients with cancer that has certain genetic changes called AKT mutations. Ipatasertib is in a class of medications called protein kinase B (AKT) inhibitors. It may stop the growth of cancer cells and may kill them.

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 ipatasertib orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) during screening and on study, as well as during follow-up as clinically necessary. Patients undergo biopsies and blood sample collection on study.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 1 year.

THE MATCH SCREENING TRIAL:

Please see NCT02465060 for information on the MATCH Screening Protocol and applicable documents.

Inclusion Criteria:

• Patients must have met applicable eligibility criteria in the Master MATCH Protocol EAY131/ NCI-2015-00054 prior to registration to treatment subprotocol

• Patients must have an AKT mutation as determined via the MATCH Master Protocol

• Patients with breast cancer are excluded

• Patients with castration-resistant prostate cancer should maintain castrate levels of testosterone (i.e., with gonadotropin-releasing hormone (GnRH) agonists or through surgical castration). Patients are allowed to continue abiraterone acetate/prednisone with Ipatasertib if the patient just progressed on abiraterone acetate/prednisone

• Patients must not have known hypersensitivity to Ipatasertib 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 with diabetes or risk for hyperglycemia are eligible. Patients with diabetes mellitus should be on a stable dose of oral hypoglycemic agents for >= 4 weeks and appropriate diet. 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)
  • Patients not on a stable dose of oral hypoglycemic medication for >= 4 weeks and appropriate diet
  • Insulin required for routine diabetic management and control
  • More than two oral hypoglycemic medications required for routine diabetic management and control
  • Glycosylated hemoglobin (hemoglobin A1C) >= 7.5%

• Prior PI3K and mTOR inhibitors are allowed, including in the metastatic setting. Prior AKT inhibitors are excluded

• Patients with a history of inflammatory bowel diseases (Crohn's disease and ulcerative colitis) or active diverticulitis are not eligible

• Patients may not have received strong inhibitors or potent inducers or substrates of CYP3A4/5 within 2 weeks before the first dose of study treatment (3 weeks for St John's wort)

• In addition to the patient contraception requirements outlined in EAY131 MATCH Master Protocol, male patients must also refrain from donating sperm for the duration of study participation, and for 4 months after completion of study

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