Study of LY3023414 for the Treatment of Recurrent or Persistent Endometrial Cancer

Inclusion Criteria

• Patients must have recurrent or persistent endometrial carcinoma 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, transitional cell carcinoma, and carcinosarcoma.
• Age ≥ 18 years
• Patients must have had at least one but no more than four prior chemotherapeutic regimens for management of endometrial carcinoma (including neo-adjuvant and/or adjuvant chemotherapy). 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 tumors must have known PI3K pathway activation defined as EITHER of the following on a CLIA-approved molecular diagnostics test:
• Genomic alteration resulting in loss of PTEN function including a) whole or partial gene deletion, frame shift mutations, or non-sense mutations. Missense mutations in PTEN will not be considered qualifying.
• A previously characterized activating mutation in any component of the pathway including: PIK3CA, AKT1, PIK3R1, PIK3R2, mTOR
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Resolution of adverse effects of recent surgery, radiotherapy, or chemotherapy to Grade ≤1 prior to first study treatment (with the exception of alopecia or neuropathy).
• Patients must have measurable disease. Measurable disease is defined by RECIST (version 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.
• No active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection).
• Any other prior therapy directed at the malignant tumor, including immunologic agents and radiotherapy, must be discontinued at least 2 weeks prior to first study treatment.
• Adequate hematologic defined by the following laboratory results obtained within 14 days prior to first study treatment:
• Absolute neutrophil count (ANC) ≥1500/10^9dL
• Platelet count ≥ 100,000/10^9dL
• Hemoglobin ≥ 9.0 g/dL
• Adequate hepatic function defined by the following laboratory results obtained within 14 days prior to first study treatment:
• Total bilirubin≤1.5x the upper limit of normal (ULN)
• AST and ALT ≤ 3.0x ULN (unless the patient has Gilbert's Syndrome, in which case AST and ALT ≤ 5.0x ULN is permitted
• Albumin ≥ 3.5 g/dL
• Adequate renal function defined by the following laboratory results obtained within 14 days prior to first study treatment:
• Serum creatinine≤1.5x ULN OR creatinine clearance ≥50 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation
• For all patients (regardless of known diabetes) the following is required at screening: Fasting blood glucose ≤ 135 mg/dL (7.49 mmol/L) and HbA1c ≤7.0%
• For patients of childbearing potential, agreement to use two effective forms of contraception (e.g., surgical sterilization, a reliable barrier method, birth control pills, or contraceptive hormone implants) and to continue its use for the duration of the study and for 30 days after the last LY3023414 dose.
• Patients must have been enrolled, or agree to consent to the companion genomic profiling study MSKCC IRB# 12-245.
• Willingness to sign written informed consent to this study.

Exclusion Criteria

• Patients with known concurrent activating RAS/RAF mutation or loss of function mutation or deletion in NF1 of NF2 resulting in MAP kinase pathway activation.