ONC201 in Recurrent or Metastatic Type II Endometrial Cancer Endometrial Cancer

Study Overview
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Brief Summary
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This is a a Simon's two-stage, non-randomized, open label, 2-arm Phase II trial of ONC201 in women with metastatic or recurrent Type II endometrial cancer who failed at least 1 prior chemotherapy regimen.

Official Title
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A Phase II Study of ONC201 in Recurrent or Metastatic Type II Endometrial Cancer

Conditions
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Endometrial Cancer Recurrent

Intervention / Treatment
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* Drug: ONC201


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed metastatic or recurrent Type II EC (serous, clear cell, carcinosarcoma, adenosquamous and mixed histologies). 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. Availability of at least 12 unstained slides from archival FFPE tumor tissue. For Arm A, patients must have disease that is amenable to biopsy and must be willing to provide consent for a tumor biopsy at baseline (within 30 days of beginning ONC201) and at least 1 on-treatment tumor biopsy. Must have radiographic disease progression after at least 1 line of systemic cytotoxic therapy for metastatic disease or with progression within 12 months of completing adjuvant chemotherapy. Age > 18 years. ECOG performance status of 0, 1, or 2. Patients must have adequate bone marrow, hepatic and renal function as defined below: Leukocytes > 3,000/mcL Absolute neutrophil count > 1,500/mcL Platelets > 100,000/mcL Total bilirubin ≤1.5 ULN AST/ALT (SGOT/SGPT) < 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 Life expectancy at least 3 months. Ability to understand and willingness to sign a written informed consent and HIPAA consent document. 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: No prior treatment with ONC201. 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. 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. 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. The subject is unable to swallow capsules. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of ONC201 (uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection). Patients receiving any other investigational agents. Patients with symptomatic brain metastases are excluded. Patients with asymptomatic and treated 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. Uncontrolled intercurrent 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. 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. Known HIV-positive patients on combination antiretroviral therapy. Known history of HBV or HCV infection. 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. Pregnant or breast feeding.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Biopsy-mandated<br> | Drug: ONC201<br>* ONC201<br>|
| Experimental: Biopsy-optional<br> | Drug: ONC201<br>* ONC201<br>|
| Experimental: Dosing twice per week on two consecutive days<br> | Drug: ONC201<br>* ONC201<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progress-free survival | PFS2 | 2 months |