Phase 1 Trial of ONC201 for Chemoprevention in Colorectal Cancer
The purpose of this phase I trial is to test the safety and cancer preventive effects of different doses of ONC201 in people with familial adenomatous polyposis (FAP) or a history of multiple polyps. People with familial adenomatous polyposis (FAP) or a history of multiple polyps are at higher than average risk of developing colorectal cancer. ONC201, now known as dordaviprone, is a drug that may stop cancer cells from growing. This drug has been shown in previous studies to cause cancer cell death but not harm normal cells. If successful, this study may help us develop a new option for colorectal cancer prevention.
• Be identified as high risk for recurrent colorectal adenomas, as defined by:
‣ A diagnosis of FAP AND/OR
⁃ Findings of either \> 5 small (less than 1 cm) adenomas OR \>= 3 with at least one \>= 10 mm on most recent colonoscopy performed in the past 5 years
• Be \>= 18 years of age on day of signing informed consent
• Have an Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
• Leukocytes \>= 3,000/microliter
• Absolute neutrophil count \>= 1,000/microliter
• Platelets \>= 100,000/microliter
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum (glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase (\[SGPT\]) =\< 1.5 x institutional upper limit of normal
• Creatinine =\< 1.5 x institutional upper limit of normal
• Participant is due to undergo a standard of care lower gastrointestinal (GI) colonoscopy for detection and removal of colorectal polyps. On this colonoscopy, participant is required to have:
‣ Two (2) adenomatous polyps of at least five (5) mm in size
⁃ At least one (1) polyp within reach of a flexible sigmoidoscope (which will be retained in the colon or rectum and marked)
⁃ In addition to polypectomy, six (6) biopsies of normal colonic mucosa \>= 1 cm from a collected polyp will also be collected
• Willing to undergo a second, research intent endoscopic procedure (either sigmoidoscopy or colonoscopy), approximately 12 weeks after initiating ONC201 treatment
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
• Life expectancy of at least 5-years
• ONC201 is an imipridone agent with the potential for teratogenic or abortifacient effects. For this reason and because imipridones potential teratogenic effects are unknown, men and women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for four weeks after study treatment is completed. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should STOP the study medication and inform her study physician immediately
• Ability to understand and the willingness to sign a written informed consent document