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Akt / ERK inhibitor ONC201 in Treating Patients with Recurrent or Metastatic Endometrial Cancer

Trial Status: Active

This phase II trial studies how well Akt / ERK inhibitor ONC201 works in treating patients with endometrial cancer that has come back or has spread to other places in the body. Akt / ERK inhibitor ONC201 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Inclusion Criteria

  • 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
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) criteria version (v.) 1.1
  • 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
  • Available archived tissue biopsies will be provided for correlative studies
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 upper limit of normal (ULN)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) (serum glutamic-oxaloacetic transaminase [SGOT]/serum glutamate pyruvate transaminase [SGPT]) =< 2 ULN
  • Creatinine =< 1.5 ULN OR creatinine clearance >= 60 Ml/min/1.73 m^2 for patients with creatinine levels above ULN calculated using Calvert formula
  • Prior chemotherapy, hormonal and radiation therapy administered in the adjuvant setting will be allowed
  • Life expectancy at least 3 months
  • Ability to understand and willingness to sign a written informed consent and Health Insurance Portability and Accountability Act (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
  • Patients who are receiving any therapeutic agent for non-neoplastic indication, determined on case by case basis by the principal investigator

Exclusion Criteria

  • No prior treatment with ONC201
  • Patients who have had hormonal therapy, 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; patients with side-effects Common Terminology Criteria for Adverse Events (CTCAE) =< grade 1 due to previous therapy are included
  • 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
  • Patients receiving any other investigational agents
  • 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
  • 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 human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy
  • Known history of hepatitis B virus (HBV) or hepatitis C virus (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


Fox Chase Cancer Center
Status: ACTIVE
Contact: Gina Marie Mantia Smaldone
Phone: 215-728-3175
Temple University Hospital
Status: ACTIVE
Contact: Enrique Hernandez
Phone: 215-707-3002


I. Determine the efficacy of single agent Akt/ERK inhibitor ONC201 (ONC201) dosed 625 mg orally, once every week in women with metastatic or recurrent endometrial cancer.


I. Evaluation of the safety profile of single agent ONC201 in women with recurrent or metastatic endometrial cancers.

II. To determine the duration of response and duration of stable disease in patients treated with ONC201 dosed 625 mg orally, once every week.

III. To determine the median progression free survival (PFS) of patients treated with ONC201 dosed 625 mg orally, once every week.


Patients receive Akt/ERK inhibitor ONC201 orally (PO) once a week. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Fox Chase Cancer Center

Principal Investigator
Gina Marie Mantia Smaldone

  • Primary ID GYN-106
  • Secondary IDs NCI-2017-01060
  • ID NCT03099499