A Phase II Study of Akt Inhibitor MK2206 in the Treatment of Recurrent Platinum-Resistant Ovarian, Fallopian Tube, or Peritoneal Cancer

Inclusion Criteria

• Participants must have histologically or cytologically confirmed high grade (grade 2 or 3) serous ovarian, fallopian tube, or primary peritoneal cancer; participants with mixed histology are eligible if the serous component is the dominant histological subtype
• Participants must have measurable disease as defined by RECIST 1.1 criteria
• Participants must have evidence of a defect in the PI3K/AKT pathway, defined by A) evidence of loss of PTEN by immunohistochemistry in a CLIA-certified assay or B) documentation of PIK3CA or AKT mutation in a CLIA-certified assay; for patients without prior CLIA-certified evidence of a PI3K/AKT pathway defect, PTEN testing will be performed by immunohistochemistry in a CLIA-certified assay; availability of a formalin fixed paraffin embedded (FFPE) block of cancer tissue from the original or most recent biopsy must be available for mutational and immunohistochemical analysis
• Prior therapy:
• Prior chemotherapy must have included a first-line platinum-based regimen with or without consolidation chemotherapy
• Patients may have received up to 2 lines of therapy (including cytotoxic or biological and/or targeted therapies) in the recurrent setting
• Prior hormonal therapy is acceptable and will not count as an additional line of therapy
• Patients may not have previously received prior AKT or PI3 kinase pathway inhibitors (including mTOR inhibitors)
• Patients should have platinum-resistant disease, where platinum resistance is defined as having progressive disease within 6 months of receipt of prior platinum therapy
• Life expectancy of greater than 6 months
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Karnofsky > 60%)
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Hemoglobin >= 8.0 g/dL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) 60 mL/min/1.73 m^2 for subjects with creatinine levels about institutional normal
• Toxicities of prior therapy (excepting alopecia) should be resolved to less than or equal to grade 1 as per NCI-CTCAE v4.0
• Patients must be able to tolerate oral medications and not have gastrointestinal illnesses that would preclude absorption of MK-2206
• The effects of MK-2206 on the developing human fetus are unknown; for this reason, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study
• Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered to grade 1 or less (excepting alopecia) due to agents administered more than 4 weeks earlier
• Participants may not be receiving any other study agents
• Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-2206
• Participants receiving any medications or substances that are strong inhibitors or inducers of CYP450 3A4 are ineligible; lists including medications and substances known or with the potential to interact with the CYP450 3A4 isoenzymes are provided in Appendix