Akt Inhibitor MK2206 in Treating Patients With Recurrent or Advanced Endometrial Cancer

Inclusion Criteria:

• Participants must have histologically confirmed recurrent or persistent carcinoma of endometrial origin, which is refractory to curative therapy or established treatments; histologic confirmation of the original primary tumor is required; patients with the following histologic epithelial cell types are eligible: endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.), mucinous adenocarcinoma, squamous cell carcinoma, and transitional cell carcinoma; tumors of endometrial histotype that arise from endometriosis are eligible
• All patients must have measurable disease as defined by RECIST 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by CT, MRI or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI
• Patients must have had one prior chemotherapeutic regimen for management of endometrial carcinoma initial treatment may include chemotherapy, chemotherapy and radiation therapy, and/or consolidation/maintenance therapy; chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen
• Patients are allowed to receive, but are not required to receive, one additional prior treatment regimen (including a single chemotherapeutic, a combination of chemotherapeutics, or an anti-angiogenic drug such as bevacizumab) for management of their recurrent or persistent disease; prior hormonal therapy is allowed and does not count towards this prior regimen
• Patients must have NOT received any class of drugs targeted to the PI3K pathway (such has PI3K inhibitors or mTOR inhibitors) for management of recurrent or persistent disease
• Life expectancy of greater than 6 months
• ECOG performance status =< 2 (Karnofsky >50%)
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Total bilirubin within normal institutional limits
• AST (SGOT)/ALT (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
• HgA1c =< 7.5% and fasting blood glucose less than 130mg/dL
• Availability of a formalin fixed paraffin embedded (FFPE) block of cancer tissue from the original or most recent biopsy for mutational analysis
• Women of childbearing potential must use two forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a patient become pregnant or suspect she is pregnant while she is participating in this study, she should inform the treating physician immediately
• Toxicities of prior therapy (excepting alopecia) should be resolved to =< grade 1 per the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4
• MK-2206 is an oral medication; patients must be able to tolerate oral medications and not have gastrointestinal illnesses that would preclude absorption of MK-2206
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered to =< grade 1 (excepting alopecia) from adverse events (as per the revised NCI CTCAE version 4) due to agents administered more than 3 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; should patients develop brain metastases while on trial and have clinical benefit from MK-2206 otherwise, patients may continue on drug after clinical management of the brain metastases with the permission of the principal investigator. MK-2206 should be restarted between 3 and 6 weeks after the last radiation treatment
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-2206
• Patients requiring any medications or substances that are strong inhibitors or inducers of CYP 450 3A4 are ineligible
• Preclinical studies demonstrated the potential of MK-2206 for induction of hyperglycemia in all preclinical species tested; patients with diabetes or in risk for hyperglycemia should not be excluded from trials with MK-2206, but the hyperglycemia should be well controlled on oral agents before the patient enters the trial. HgbA1c > 7.5% or fasting glucose greater than 130mg/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
• Due to a high incidence of bradycardia by Holter monitor, preexisting bundle branch 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
• Pregnant women are excluded from this study; 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
• MK-2206 is an oral medication; patients who are unable to tolerate oral medication are not eligible; patients with signs and symptoms of bowel obstruction or with uncontrolled, persistent diarrhea will be excluded
• 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
• HIV-positive individuals on combination antiretroviral therapy are ineligible
• Patients may not use natural herbal products or other "folk remedies" while participating in this study