Intervention: MK-2206
Trial phase: Phase 2
SMILES: NC1(c2ccc(-c3nc4ccn5c(=O)[nH]nc5c4cc3-c3ccccc3)cc2)CCC1
Sex: Female
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 5
Group description: Akt inhibitor MK2206 will be taken PO once a week for four weeks (one cycle). Treatment will continue for as long as a subject is benefiting from the study drug.

Akt Inhibitor MK2206: Given PO

Laboratory Biomarker Analysis: Correlative studies
Eligibility criteria:
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]) < 2.5 X institutional upper limit of normal
Creatinine within normal institutional limits or creatinine clearance > 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 C; if the participant is taking any agent known to affect or with the potential to affect CYP450 3A4 isoenzymes, this should be discussed with the overall PI
Preclinical studies demonstrated the potential of MK-2206 for induction of hyperglycemia in all preclinical species tested; patients with diabetes or at risk for hyperglycemia are eligible for this study, but the hyperglycemia should be well controlled on oral agents before the patient enters the trial; a fasting serum glucose of > 130 mg/dL or a HgbA1c > 7.5 mg/dL will exclude patients from entry on study; patients requiring insulin for control of their hyperglycemia are excluded from entry on this study
Preclinical studies indicated transient changes in QTc interval during MK-2206 treatment; prolongation of QTc interval is potentially a safety concern while on MK-2206 therapy; cardiovascular: baseline QTcF > 450 msec (male) or QTcF > 470 msec (female) will exclude patients from entry on study; a list of medications that may cause QTc interval prolongation are listed in Appendix D, and should be avoided by patients entering on trial
Due to a high incidence of bradycardia by Holter monitor, preexisting significant heart block or baseline bradycardia due to cardiac disease will exclude patients from treatment with MK-2206
Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Current signs and/or symptoms of bowel obstruction
Current dependency on IV hydration or TPN
Pregnant women are excluded from this study because MK-2206 is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with MK-2206, breastfeeding should be discontinued if the mother is treated with MK-2206; these potential risks may also apply to other agents used in this study
Individuals with a history of a different malignancy are ineligible except for the following circumstances; individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy; individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: breast cancer in situ, cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin
Human immunodeficiency virus (HIV)-positive individuals on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with MK-2206; iIn addition, these individuals are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated
Patients may not use natural herbal products or other "folk remedies" while participating in this study