Sulindac for Pancreatic Cancer Prevention

Recruiting at 3 trial locations

Overseen By Peter Allen, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Duke University

Must not be taking: Corticosteroids, NSAIDs

Disqualifiers: Pancreatic adenocarcinoma, Renal insufficiency, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: 1

Duration: 3 years

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing whether sulindac, an anti-inflammatory medication, can help prevent the progression of high-risk pancreatic growths in patients. The goal is to see if reducing inflammation can stop these growths from getting worse or turning into cancer. Sulindac is a promising treatment for chronic pancreatitis by reducing inflammation and tissue scarring.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot participate if you take a systemic corticosteroid or NSAID more than 3 times a week. If you are on these medications, you may need to stop or reduce them to join the trial.

What data supports the effectiveness of the drug Sulindac for pancreatic cancer prevention?

Sulindac, a type of nonsteroidal anti-inflammatory drug (NSAID), has been shown to help prevent colorectal cancer in some studies. While there is no direct evidence for its effectiveness in preventing pancreatic cancer, other NSAIDs like aspirin have shown potential in reducing the risk of pancreatic cancer, suggesting that Sulindac might have similar benefits. ^{1 2 3 4 5}

Is sulindac generally safe for human use?

Sulindac, a type of nonsteroidal anti-inflammatory drug (NSAID), has been studied for its potential to prevent various cancers, including colorectal and lung cancer. While specific safety data for pancreatic cancer prevention is not available, sulindac has been used in clinical trials for other conditions, suggesting it is generally considered safe for human use in those contexts. ^{1 4 5 6 7}

How does the drug sulindac differ from other treatments for pancreatic cancer?

Sulindac is unique in its ability to inhibit pancreatic cancer growth by targeting specific enzymes like AKR1B10, which are involved in cancer development. It also shows potential in combination therapies, enhancing the effects of other drugs by inhibiting pathways like NF-kappaB and COX, which are often overactive in pancreatic cancer. ^{5 7 8 9 10}

Research Team

Peter Allen, MD

Principal Investigator

Duke University

Eligibility Criteria

This trial is for adults aged 21-85 with high-risk IPMN of the pancreas, who are medically fit for an endoscopic ultrasound and can undergo imaging studies. Women able to have children must use contraception during the study. Exclusions include heart failure, recent cancer treatments, certain surgical histories, severe drug reactions to contrast agents or NSAIDs, recent heart attacks or bypass surgery, and ongoing renal insufficiency or other conditions that conflict with sulindac use.

Inclusion Criteria

I am between 21 and 85 years old.

I am willing to use birth control during the study.

I am able to care for myself and perform daily activities.

Exclusion Criteria

I have been diagnosed with pancreatic cancer.

You have a history of severe allergic reactions to NSAIDs or aspirin, or have had stomach ulcers or bleeding from using NSAIDs.

I have kidney, heart, or stomach issues that may prevent me from taking certain medications.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

3 months

1 visit (in-person)

Treatment

Participants receive sulindac or placebo twice daily for up to 3 years with regular assessments

3 years

Bi-annual visits (in-person), bi-monthly phone calls

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Annual imaging and EUS assessments

Treatment Details

Interventions

• Placebo
• Sulindac

Trial Overview The trial tests if sulindac (a nonsteroidal anti-inflammatory drug) can prevent progression of pancreatic lesions in patients with high-risk IPMNs compared to a placebo. Participants will receive either sulindac (400 mg daily) or a placebo alongside standard surveillance over up to three years. The process includes random assignment into groups considering prior dysplasia and metformin usage.

Participant Groups

Group I: Sulindac Experimental Treatment 1 Intervention

Patients will be randomized to receive standard radiographic/endoscopic surveillance plus sulindac. The sulindac starting dose is 200 mg by mouth 2x daily. Patients will continue drug for 3 years during follow-up.

Group II: Placebo Placebo Group 1 Intervention

Patients will be randomized to receive standard radiographic/endoscopic surveillance plus placebo. Patients will continue placebo for 3 years during follow-up.

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Memorial Sloan Kettering Cancer Center

Collaborator

Trials

1,998

Recruited

602,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

References

1. England pubmed.ncbi.nlm.nih.gov

Rectal epithelial apoptosis in familial adenomatous polyposis patients treated with sulindac. [2022]

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

Chemoprevention for pancreatic cancer. [2018]

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

Targeting pancreatitis blocks tumor-initiating stem cells and pancreatic cancer progression. [2021]

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

Association between nonsteroidal anti-inflammatory drug use and the incidence of pancreatic cancer. [2019]

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

Intermittent Dosing with Sulindac Provides Effective Colorectal Cancer Chemoprevention in the Azoxymethane-Treated Mouse Model. [2018]

6. Ireland pubmed.ncbi.nlm.nih.gov

Randomized phase II trial of sulindac for lung cancer chemoprevention. [2021]

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

Growth inhibition and apoptosis induction of Sulindac on Human gastric cancer cells. [2019]

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

Sulindac inhibits pancreatic carcinogenesis in LSL-KrasG12D-LSL-Trp53R172H-Pdx-1-Cre mice via suppressing aldo-keto reductase family 1B10 (AKR1B10). [2021]

9. Greece pubmed.ncbi.nlm.nih.gov

Phospho-sulindac inhibits pancreatic cancer growth: NFATc1 as a drug resistance candidate. [2021]

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

Suppression of pancreatic tumor growth by combination chemotherapy with sulindac and LC-1 is associated with cyclin D1 inhibition in vivo. [2020]