ONC201 in Recurrent or Metastatic Type II Endometrial Cancer Endometrial Cancer

• ClinicalTrials.gov Identifier: NCT03485729
• Recruitment Status: Active, not recruiting
• First Posted: April 2, 2018
• Last Update Posted: March 14, 2022
• Sponsor: Chimerix
• Information provided by (Responsible Party): Chimerix

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Endometrial Cancer Recurrent	Drug: ONC201	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of ONC201 in Recurrent or Metastatic Type II Endometrial Cancer
• Actual Study Start Date: March 21, 2018
• Estimated Primary Completion Date: August 31, 2022
• Estimated Study Completion Date: December 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Biopsy-mandated	Drug: ONC201; ONC201
Experimental: Biopsy-optional	Drug: ONC201; ONC201
Experimental: Dosing twice per week on two consecutive days	Drug: ONC201; ONC201

Outcome Measures

Primary Outcome Measures :

1. Progress-free survival [ Time Frame: 2 months ]
   PFS2

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, New Jersey

Rutgers, The State University of New Jersey

New Brunswick, New Jersey, United States, 08903

United States, North Carolina

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States, 27599

United States, Pennsylvania

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States, 19111

Sponsors and Collaborators

Chimerix

More Information

• Responsible Party: Chimerix
• ClinicalTrials.gov Identifier: NCT03485729
• Other Study ID Numbers: ONC012
• First Posted: April 2, 2018
• Last Update Posted: March 14, 2022
• Last Verified: March 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Endometrial Neoplasms; Recurrence; Disease Attributes; Pathologic Processes; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; TIC10 compound; Antineoplastic Agents