36 Participants Needed

ONC201 for Colorectal Cancer Prevention

Recruiting at 5 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on testing a new treatment called ONC201 to prevent colorectal cancer in individuals at high risk due to familial adenomatous polyposis (FAP) or a history of multiple polyps. The trial aims to assess the safety of ONC201, identify potential side effects, and determine the optimal dose. ONC201 may inhibit tumor growth by blocking certain enzymes necessary for cell growth. It is suitable for those diagnosed with FAP or who have had more than five small polyps or at least three larger polyps during a colonoscopy in the past five years. Participants should also be willing to undergo additional procedures such as blood tests and colonoscopies. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, you cannot be on any other investigational agents or have taken them in the past four weeks.

Is there any evidence suggesting that ONC201 is likely to be safe for humans?

Research shows that ONC201 looks promising for safety and cancer prevention. In animal studies, ONC201 greatly reduced the number of colon tumors. Female mice treated with ONC201 had up to 75% fewer tumors than those without the treatment. This suggests ONC201 might help stop tumors from forming.

Although detailed human safety data for ONC201 is not yet available, its testing in a phase 1 trial means researchers are still determining its safety for people. Phase 1 trials usually focus on finding the safest dose and monitoring for any side effects. Researchers are studying ONC201 because it might block certain enzymes that tumors need to grow, which could be important for its safety and effectiveness.

Overall, while early research is encouraging, more information is needed to fully understand ONC201's safety in humans. Joining the trial is important to help gather this information.12345

Why do researchers think this study treatment might be promising?

Unlike the standard of care for colorectal cancer prevention, which typically involves surgery, chemotherapy, and radiation, ONC201 offers a unique approach by targeting specific pathways in cancer cells. Researchers are excited about ONC201 because it works by activating a stress response pathway that can lead to cancer cell death while sparing healthy cells. This new mechanism of action could potentially offer a safer and more effective alternative to current treatments, with fewer side effects. Additionally, the oral administration of ONC201 makes it a more convenient option for patients compared to traditional therapies.

What evidence suggests that ONC201 might be an effective treatment for colorectal cancer prevention?

Research suggests that ONC201, the investigational treatment in this trial, may help prevent colorectal cancer. Studies in mice have shown that ONC201 can reduce the number of colon tumors and non-cancerous growths called adenomas. This effect likely occurs because ONC201 increases a protein called TRAIL, which helps destroy cancer cells, and triggers cell death based on the dose given. Additionally, ONC201 turns off signals inside cancer cells, such as ERK and AKT, that help them survive, thereby stopping their growth. These findings strongly support testing ONC201 in humans to determine its potential to prevent cancer in people with a history of polyps.36789

Who Is on the Research Team?

AG

Alexander G Raufi

Principal Investigator

Rhode Island Hospital

Are You a Good Fit for This Trial?

This trial is for adults at high risk of colorectal adenomas, specifically those with familial adenomatous polyposis (FAP) or a history of multiple polyps. Participants must be in good health with an ECOG performance status <=1 and have normal organ function. They should not have had invasive cancer treatments within the last 3 years, except for certain skin cancers or cervical cancer in situ.

Inclusion Criteria

I am willing and able to follow the study's schedule and procedures.
I am at high risk for colorectal adenomas due to FAP or having more than 5 small adenomas or at least 3 with one being larger than 10mm.
Leukocytes >= 3,000/microliter
See 13 more

Exclusion Criteria

I have a history of Lynch syndrome.
I am not pregnant or nursing, as the treatment may harm the baby.
I am not currently on any experimental drugs and haven't been for the last 4 weeks.
See 5 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ONC201 orally once weekly or once every 3 weeks for 12 weeks. Blood, tissue biopsy, and sigmoidoscopy/colonoscopy are conducted throughout the study.

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • ONC201
Trial Overview The trial is testing ONC201's safety and optimal dosage to prevent colorectal cancer in patients prone to developing polyps. It involves procedures like colonoscopy, biopsy collection, and questionnaires to monitor effects on tumor cell growth inhibition by targeting specific enzymes.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Prevention (ONC201, biopsy, sigmoidoscopy, colonoscopy)Experimental Treatment6 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Citations

Oral administration of TRAIL-inducing small molecule ...ONC201 reduced colon tumor incidence in Apcmin/+ mice​​ Based on these data, two doses of ONC201, 25 mg/kg BW (low dose) and 50 mg/kg BW (high-dose), were ...
Abstract 4780: TRAIL-inducing imipridone ONC201/TIC10 ...More recently, we have shown that ONC201 induces TRAIL and apoptosis in a dose-dependent manner and reduces adenoma formation in the Apcmin/+ ...
Study Details | Testing ONC201 to Prevent Colorectal CancerAn unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...
prevention of colorectal cancer by onc201 - NIH RePORTERA phase I clinical trial with ONC201 in patients with advanced solid tumors, showed some evidence of efficacy (stable disease) at doses that were well ...
Karmanos Researcher Co-discovered Compound, Led to ...Preclinical and clinical trials revealed that ONC201 worked in multiple ways: it shut down survival signals inside cancer cells (ERK and AKT), ...
NCT05630794 | Testing for Safety and Colorectal Cancer ...This phase I trial tests the safety, side effects, and best dose of ONC201 in preventing colorectal cancer in patients with familial adenomatous polyposis ...
Testing for Safety and Colorectal Cancer Preventive Effects of ...This phase I trial tests the safety, side effects, and best dose of ONC201 in preventing colorectal cancer in patients with familial adenomatous polyposis ...
Small molecule ONC201/TIC10 targets chemotherapy ...ONC201/TIC10 is a promising agent for colorectal cancer therapy that targets both non-CSCs and CSCs in an Akt-Foxo3a-TRAIL-dependent manner.
Dordaviprone – Application in Therapy and Current ...Colorectal Cancer Prevention Trial: This Phase 1 trial is testing dordaviprone's safety and effectiveness in preventing colorectal cancer in high-risk ...
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