Eflornithine + Sulindac for Colorectal Cancer Prevention

(PACES Trial)

Recruiting at 1010 trial locations

Overseen By Raed Al-Rajabi

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Southwest Oncology Group

Must not be taking: Corticosteroids, NSAIDs, Anticoagulants

Disqualifiers: High cardiovascular risk, Uncontrolled hypertension, Gastric/duodenal ulcer, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 3 years

354 Participants Needed

Trial Summary

What is the purpose of this trial?

The investigators hypothesize that the combination of eflornithine and sulindac will be effective in reducing a three-year event rate of adenomas and second primary colorectal cancers in patients previously treated for Stages 0 through III colon or rectal cancer.

Will I have to stop taking my current medications?

The trial requires that you do not take certain medications regularly, such as intravenous corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), or anticoagulants. You can use NSAIDs for up to 10 days per month, and aspirin is limited to a maximum dose of 100 mg per day or two 325 mg tablets per week. Inhaled steroids are allowed.

What data supports the effectiveness of the drug combination Eflornithine and Sulindac for colorectal cancer prevention?

Research shows that the combination of Eflornithine (also known as DFMO) and Sulindac is effective in preventing the development of colorectal adenomas (small growths that can lead to cancer) in people at high risk. This combination works better than either drug alone and has been a significant advancement in preventing these growths with minimal side effects. ^{1 2 3 4 5}

Is the combination of Eflornithine (DFMO) and Sulindac safe for humans?

The combination of Eflornithine (DFMO) and Sulindac has been studied for safety, and it was not associated with any serious toxicity in clinical trials. However, there was a non-significant trend of mild hearing issues in some patients, which may be linked to genetic factors. ^{1 3 6 7 8}

How is the drug Eflornithine + Sulindac unique for colorectal cancer prevention?

The combination of Eflornithine (DFMO) and Sulindac is unique because it targets polyamines, which are compounds involved in cell growth, to prevent colorectal cancer. This drug combination has shown a significant reduction in the recurrence of high-risk adenomas, making it a promising option for those at high risk of colorectal cancer. ^{1 3 6 8 9}

Research Team

Jason A. Zell

Principal Investigator

University of California, Irvine

Eligibility Criteria

This trial is for adults who've had Stage 0-III colon or rectal cancer and completed surgery a year ago, with no current evidence of disease. They must have finished chemo and radiation at least 30 days prior, be able to swallow pills, not take certain drugs regularly (like NSAIDs), and have stable vital signs. Pregnant women or those with high cardiovascular risks are excluded.

Inclusion Criteria

I had surgery for colon or rectal cancer that was stage 0-III, over a year ago.

I am not regularly taking steroids, NSAIDs more than 10 days a month, or blood thinners.

I had surgery for colon or rectal cancer that was stage 0-III, over a year ago.

Exclusion Criteria

I have a high risk of heart problems and my high blood pressure is not under control.

I am scheduled for more chemotherapy or radiation therapy.

I have had a stomach or upper small intestine ulcer in the past year.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive eflornithine and sulindac or corresponding placebos daily for 3 years

3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, with analyses of colorectal event rates through year 8

5 years

Treatment Details

Interventions

• Eflornithine
• Sulindac

Trial Overview The study tests if eflornithine combined with sulindac can prevent the return of adenomas or colorectal cancers in patients previously treated for these conditions. Participants will receive either both drugs, one drug plus a placebo, or double placebos over three years.

Participant Groups

Group I: Eflornithine plus sulindac Experimental Treatment 1 Intervention

Eflornithine two 250 mg tablets PO daily for 3 years. Sulindac one 150 mg tablet PO daily for 3 years.

Group II: Eflornithine placebo & sulindac Experimental Treatment 1 Intervention

Eflornithine placebo 2 tablets PO daily for 3 years. Sulindac one 150 mg tablet PO daily for 3 years.

Group III: Eflornithine & sulindac placebo Experimental Treatment 1 Intervention

Eflornithine two 250 mg tablets PO daily for 3 years. Sulindac placebo one tablet PO daily for 3 years.

Group IV: eflornithine placebo & sulindac placebo Placebo Group 1 Intervention

Eflornithine placebo 2 tablets, PO, daily for 3 years. Sulindac placebo, 1 tablet, PO, daily for 3 years.

Eflornithine is already approved in European Union, United States for the following indications:

Approved in European Union as Vaniqa for:

• Hirsutism
• African trypanosomiasis

Approved in United States as Vaniqa for:

• Hirsutism

Approved in United States as Iwilfin for:

• High-risk neuroblastoma

Who Is Running the Clinical Trial?

Southwest Oncology Group

Lead Sponsor

Trials

389

Recruited

260,000+

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Cancer Prevention Pharmaceuticals, Inc.

Industry Sponsor

Trials

8

Recruited

800+

Findings from Research

A clinical trial showed that a combination of low-dose eflornithine (DFMO) and sulindac reduced the incidence of high-risk adenomas by over 90% in patients at risk for colorectal cancer, suggesting a promising preventive strategy.

The ongoing Phase III trial (CPP FAP-310) is evaluating the safety and efficacy of DFMO and sulindac in preventing progression of Familial Adenomatous Polyposis (FAP), with 138 participants randomized across three treatment groups to assess polyp burden over 24 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of eflornithine (CPP-1X)/sulindac combination therapy versus each as monotherapy in patients with familial adenomatous polyposis (FAP): design and rationale of a randomized, double-blind, Phase III trial. Burke, CA., Dekker, E., Samadder, NJ., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Eflornithine plus Sulindac for Prevention of Progression in Familial Adenomatous Polyposis. [2020]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Eflornithine for chemoprevention in the high-risk population of colorectal cancer: a systematic review and meta-analysis with trial sequential analysis. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Role of dietary polyamines in a phase III clinical trial of difluoromethylornithine (DFMO) and sulindac for prevention of sporadic colorectal adenomas. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Concomitant DFMO and sulindac chemoprevention of colorectal adenomas: a major clinical advance. [2008]

5. United States pubmed.ncbi.nlm.nih.gov

Phase I trial of sulindac plus 5-fluorouracil and levamisole: potential adjuvant therapy for colon carcinoma. [2013]

6. England pubmed.ncbi.nlm.nih.gov

Polyamines as mediators of APC-dependent intestinal carcinogenesis and cancer chemoprevention. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Phospho-sulindac (OXT-328) combined with difluoromethylornithine prevents colon cancer in mice. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of eflornithine (CPP-1X)/sulindac combination therapy versus each as monotherapy in patients with familial adenomatous polyposis (FAP): design and rationale of a randomized, double-blind, Phase III trial. [2018]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Role of obesity in a randomized placebo-controlled trial of difluoromethylornithine (DFMO) + sulindac for the prevention of sporadic colorectal adenomas. [2021]