Samotolisib in Treating Patients with 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
• 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 Clinical Laboratory Improvement Amendments (CLIA)-approved molecular diagnostics test: * Genomic alteration resulting in loss of phosphatase and tensin homolog (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: phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), v-akt murine thymoma viral oncogene homolog 1 (AKT1), phosphoinositide-3-kinase, regulatory subunit 1 (alpha) (PIK3R1), phosphoinositide-3-kinase, regulatory subunit 2 (beta) (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 computed tomography (CT), magnetic resonance imaging (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
• Absolute neutrophil count (ANC) >= 1500/10^9 dL (within 14 days prior to first study treatment)
• Platelet count >= 100,000/10^9 dL (within 14 days prior to first study treatment)
• Hemoglobin >= 9.0 g/dL (within 14 days prior to first study treatment)
• Total bilirubin =< 1.5 x the upper limit of normal (ULN) (within 14 days prior to first study treatment)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 x upper limit of normal (ULN) (within 14 days prior to first study treatment) (unless the patient has Gilbert’s syndrome, in which case AST and ALT =< 5.0 x ULN is permitted)
• Albumin >= 3.5 g/dL (within 14 days prior to first study treatment)
• Serum creatinine =< 1.5 x ULN OR creatinine clearance >= 50 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation (within 14 days prior to first study treatment)
• For all patients (regardless of known diabetes) the following is required at screening: fasting blood glucose =< 135 mg/dL (7.49 mmol/L) and glycosylated hemoglobin (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 retrovirus-associated DNA sequence (RAS)/v-RAF-1 murine leukemia viral oncogene homolog (RAF) mutation or loss of function mutation or deletion in neurofibromin (NF)1 of NF2 resulting in mitogen-activated protein (MAP) kinase pathway activation; patients are not required to be evaluated for these alterations if not already performed
• Patients with diabetes requiring insulin or requiring more than one non-insulin hypoglycemia agents
• Patients previously treated with an mTOR, AKT, or PI3K inhibitor (including but not limited to GDC-0941, GDC-0980, BEZ235, BKM120, LY294002, PIK-75, TGX-221, XL147, XL765, SF1126, PX-866, D-87503, D-106669, GSK615, CAL101, everolimus, temsirolimus, and ridaforolimus); for agents not listed, the study principal investigator (PI) or Co-PI will make a determination
• History of myocardial infarction or unstable angina within 6 months prior to first study treatment
• New York Heart Association class II or greater congestive heart failure
• Patients with a corrected QT interval using Fridericia's formula (QTcF) interval of > 450 msec on screening electrocardiogram (ECG); Note: if > 450 msec on the first ECG, 2 additional ECGs can be ordered same day and then the average may be used to determine eligibility
• History of malabsorption syndrome or other condition that would interfere with enteral absorption
• Inability or unwillingness to swallow pills
• Clinically significant history of liver disease, including cirrhosis and current alcohol abuse
• Active hepatitis B or hepatitis C infection; patients with previously resolved hepatitis B infection are eligible; presence of positive test results for hepatitis B infection who have resolved the infection (defined by being positive for hepatitis B [HB] surface antibody [anti-HBs] and polymerase chain reaction [PCR] assay is negative for HB virus [HBV] DNA) are eligible; patients positive for hepatitis C virus (HCV) antibody are eligible only if testing for HCV ribonucleic acid (RNA) is negative
• Known human immunodeficiency virus (HIV) infection
• Need for current chronic corticosteroid therapy (>= 10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids)
• Pregnancy, lactation, or breastfeeding
• Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease)
• Major surgical procedure or significant traumatic injury within 28 days prior to day 1 or anticipation of the need for major surgery during the course of study treatment
• Known untreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control); patients with a history of treated CNS metastases are eligible, provided that they meet all of the following criteria: * Presence of measurable disease outside the CNS * No radiographic evidence of worsening upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study * No history of intracranial hemorrhage or spinal cord hemorrhage * No ongoing requirement for dexamethasone as therapy for CNS disease (anticonvulsants at a stable dose are allowed) * Absence of leptomeningeal disease
• Inability to comply with study and follow-up procedures
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator’s opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications