Single Agent ONC201 in Recurrent or Metastatic Endometrial Cancer

Inclusion Criteria: 1. Patients must have histologically confirmed metastatic or recurrent endometrial cancer. Eligible histologies include but are not limited to endometrioid, serous, clear cell, carcinosarcoma, adenosquamous, and mixed histologies. 2. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v. 1.1 3. Must have radiographic disease progression after 1 line of systemic cytotoxic therapy for metastatic disease or with progression within 12 months of completing adjuvant chemotherapy 4. Available archived tissue biopsies will be provided for correlative studies 5. Age \> 18 years. 6. Eastern Cooperative Oncology group (ECOG) performance status of 0, 1, or 2 7. Patients must have adequate bone marrow, hepatic and renal function as defined below: * Leukocytes \> 3,000/micro-liter (mcl) * Absolute neutrophil count \> 1,500/mcL * Platelets \> 100,000/mcL * Total bilirubin ≤1.5 upper limit of normal (ULN) * Aspartate aminotransferase/ Alanine aminotransferase (AST/ALT) \< 2 ULN * Creatinine ≤1.5 ULN OR * Creatinine clearance \> 60 Ml/min/1.73 m2 for patients with creatinine levels above ULN calculated using Calvert formula 8. Prior chemotherapy, hormonal and radiation therapy administered in the adjuvant setting will be allowed. 9. Life expectancy at least 3 months 10. Ability to understand and willingness to sign a written informed consent and HIPAA consent document 11. Patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of the trial and for at least 90 days after completion of treatment. Exclusion Criteria: 1. No prior treatment with ONC201 2. Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier 3. The subjects who have not recovered to baseline or CTCAE ≤ Grade 1 from related toxicity to all prior therapies will be excluded. Patients with Non-serious adverse events such as alopecia, fatigue, weakness, loss of appetite and nausea that are non-significant will not be excluded. 4. Any other prior malignancy from which the patient has been disease free for less than 3 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of any site. 5. The subject is unable to swallow capsules 6. Patients receiving any other investigational agents 7. Patients with symptomatic brain metastases are excluded. Patients with asymptomatic and treated central nervous system (CNS) metastases may participate in this trial. The patient must have completed any prior treatment for CNS metastases \> 28 days prior to study entry including radiotherapy or surgery. Steroids for the treatment of brain metastasis are not permitted, and patients must be stable off steroid treatment for 4 weeks prior to enrollment 8. Uncontrolled inter-current illness including, but not limited to ongoing or active infection. Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism. 9. Active inflammatory gastrointestinal disease, chronic diarrhea (unless related to underlying malignancy or prior related treatment) or history of abdominal fistula, gastrointestinal perforation, peptic ulcer disease, or intra-abdominal abscess within 6 months prior to study enrollment. Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed. 10. Known Human Immunodeficiency Virus (HIV)-positive patients on combination antiretroviral therapy 11. Known history of Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection. 12. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, or in the judgment of the investigator would make the patient inappropriate for entry into the study. 13. Pregnant or breast feeding. Refer to section 4.4 for further details.