Eflornithine + Sulindac for Colorectal Cancer Prevention

(PACES Trial)

Not currently recruiting at 1022 trial locations

Overseen By Leon C. Hwang

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a combination of two drugs, eflornithine (also known as Vaniqa, Iwilfin, Ornidyl, α-difluoromethylornithine, or DFMO) and sulindac, can prevent new adenomas (a type of tumor) and additional colorectal cancers in individuals previously treated for early-stage colon or rectal cancer. The trial includes different groups where participants may receive both drugs, one of the drugs, or a placebo (a non-active substance) to compare effectiveness. Individuals who have undergone surgery for Stage 0-III colon or rectal cancer and show no current signs of cancer might be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer prevention treatments.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using eflornithine with a non-steroidal anti-inflammatory drug (NSAID) like sulindac is safe and effective in preventing colorectal adenomas, which are polyps that can lead to cancer. Studies have found that this combination therapy reduces the chance of these polyps returning in individuals with a history of advanced colorectal tumors.

Sulindac, an NSAID, is known for its role in preventing colorectal cancer. It has undergone testing in human clinical trials and is considered safe for treating colorectal polyps. However, its efficacy and safety as a standalone treatment for this purpose remain unclear.

Past studies indicated that using eflornithine and sulindac together did not significantly slow disease progression compared to using either drug alone, but both drugs have been well-tolerated in clinical settings. Participants can therefore expect a reasonable level of safety if they join a trial involving these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using eflornithine and sulindac for colorectal cancer prevention because these drugs offer a unique approach. Unlike standard treatments, which often focus on surgical removal or chemotherapy, eflornithine and sulindac work by interfering with specific biochemical pathways that promote cancer cell growth. Eflornithine inhibits an enzyme called ornithine decarboxylase, which is crucial for cell division, while sulindac reduces inflammation and related cancer risk. This combination could potentially prevent cancer before it even starts, offering a promising strategy for high-risk individuals.

What evidence suggests that this trial's treatments could be effective for colorectal cancer prevention?

This trial will evaluate the effectiveness of eflornithine and sulindac, both separately and in combination, for colorectal cancer prevention. Studies have shown that using eflornithine with sulindac can significantly reduce the recurrence of adenomatous polyps, which are colon growths that can become cancerous. This combination treatment has successfully lowered the number of these polyps in individuals with a history of advanced colorectal tumors. Research also shows that sulindac alone can help prevent tumors, as it is a non-steroidal anti-inflammatory drug (NSAID). While eflornithine alone has produced mixed results, its combination with sulindac appears promising for reducing cancer risks. Overall, evidence suggests that eflornithine and sulindac together may help prevent colorectal cancer. ^{1 2 4 6 7}

Who Is on the Research Team?

Jason A. Zell

Principal Investigator

University of California, Irvine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10686413/

Eflornithine for chemoprevention in the high-risk population ... Objectives. To evaluate the efficacy of Difluoromethylornithine (DFMO) chemoprevention in the high-risk population for colorectal cancer (CRC).

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38033490/

Eflornithine for chemoprevention in the high-risk population ... The combination therapy of DFMO effectively diminishes the occurrence of recurrent adenomas in patients with a history of advanced colorectal tumors.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1521691811000837

5 DFMO: Targeted risk reduction therapy for colorectal ... Human trials of DFMO alone have shown mixed results in cancer chemoprevention. Topical DFMO reduced by one-quarter the number of pre-malignant actinic keratoses ...

4. fda.gov fda.gov/media/172661/download

eflornithine (dfmo) tablets to reduce the risk of ... DFMO in adult patients at risk of colorectal cancer, with history of and risk for recurrent adenomas, or at risk of skin cancer were reviewed.

5. researchgate.net researchgate.net/publication/375681845_Eflornithine_for_chemoprevention_in_the_high-risk_population_of_colorectal_cancer_a_systematic_review_and_meta-analysis_with_trial_sequential_analysis

a systematic review and meta-analysis with trial sequential ... PDF | Objectives To evaluate the efficacy of Difluoromethylornithine (DFMO) chemoprevention in the high-risk population for colorectal cancer.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3227870/

DFMO: targeted risk reduction therapy for colorectal ... DFMO in combination with a non-steroidal anti-inflammatory drug (NSAID) has been shown to be safe and effective in chemoprevention of colorectal adenomas.

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa1916063

Eflornithine plus Sulindac for Prevention of Progression in ... The incidence of disease progression was not significantly lower with the combination of eflornithine and sulindac than with either drug alone.