| Eligibility |
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.
|
