PIK3CA Mutation Stratified Trial of MK-2206 in Recurrent or Advanced Endometrial Cancer

Inclusion Criteria:

• Histologically confirmed recurrent or persistent endometrial carcinoma, which is refractory to curative therapy or established treatments.
• 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 at least 10 mm when measured by CT, MRI or caliper measurement by clinical exam; or at least 20 mm when measured by chest x-ray. Lymph nodes must be at least 15 mm in short axis when measured by CT or MRI.
• Patients must have had at least one prior chemotherapeutic regimen for management of endometrial carcinoma. Initial treatment may include chemotherapy, chemotherapy and radiation therapy, and/or consolidation/maintenance therapy.
• Patients must have not received any class of drugs targeted to the PI3K pathway (including mTOR inhibitors) for management of recurrent or persistent disease.
• 18 years of age or greater
• Life expectancy of greater than 6 months
• ECOG performance status of 0, 1 or 2
• Normal organ and marrow function as outlined in the protocol
• Availability of formalin fixed paraffin embedded block of cancer tissue from the original or most recent biopsy for mutational analysis
• Women of childbearing potential must use two forms of contraception prior to study entry and for the duration of study participation.
• Toxicities of prior therapy (excepting alopecia) should be resolved to grade 1 or lower per CTCAE version 4.
• Subjects with treated limited-stage basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the breast or cervix are eligible. Subjects with stage I or II cancer treated with curative intent with no evidence of recurrent disease 5 years following diagnosis are eligible.
• Patients must be able to tolerate oral medications and not have gastrointestinal illnesses that would preclude absorption of MK-2206

Exclusion Criteria:

• 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 from adverse events due to agents administered more than 4 weeks earlier.
• Participants may not be receiving any other study agents
• Participants with known brain metastases
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-2206
• Patients who require medications or substances that are strong inhibitors of inducers of CYP 450 3A4
• Patients with diabetes or in risk of hyperglycemia should not be excluded, but the hyperglycemia should be well controlled on oral agents before the patient enters the trial
• Baseline QTcF > 470msec
• 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 or breastfeeding women
• Patients who are unable to tolerate oral medication. Patients with signs and symptoms of bowel obstruction or with uncontrolled, persistent diarrhea.
• HIV-positive individuals on combination antiretroviral therapy
• Patients may not use any natural herbal products or other "folk remedies" while on study