Linaclotide for Colorectal Cancer

Not currently recruiting at 2 trial locations

Overseen By Scott Waldman, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University

Must not be taking: Linaclotide, Investigational agents

Disqualifiers: Gastroparesis, Celiac, Inflammatory bowel, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests linaclotide, a small protein, to evaluate its effectiveness in treating stages 0-3 colorectal cancer. Linaclotide prompts intestinal cells to release water and salt, potentially impacting cancer treatment. Participants will receive either linaclotide or a placebo (a harmless pill with no active ingredients) and will undergo standard procedures like colonoscopy or surgery after a week. Ideal participants are those diagnosed with stage 0-3 colorectal cancer or those who have had one or more colorectal polyps found in previous exams and are scheduled for surgery. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to significant advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on chronic anti-coagulants or non-NSAID anti-platelet agents, you may need to stop them if they can't be safely discontinued before study procedures.

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

Research shows that linaclotide is generally safe and well-tolerated. It has proven effective and safe for older adults, though some people might experience diarrhea as a side effect. Linaclotide also helps clean the bowels and has shown potential in detecting early signs of colon cancer.

These results suggest that linaclotide is safe enough for testing in a Phase 2 trial. Phase 2 trials continue to assess the safety of a treatment, indicating that linaclotide has already passed initial safety tests. However, like any medical treatment, side effects may occur. Prospective participants should discuss any concerns with a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for colorectal cancer?

Unlike the standard treatments for colorectal cancer that typically involve chemotherapy, radiation, or surgery, linaclotide is unique because it works by targeting the intestinal environment. Linaclotide, primarily used to treat irritable bowel syndrome, works by increasing fluid secretion in the intestine, which may improve the bowel's health and function. Researchers are excited about its potential to offer a novel, less invasive option that could complement or enhance the effectiveness of existing treatments. Additionally, linaclotide's oral administration makes it a convenient option for patients compared to more invasive treatments.

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

Research has shown that linaclotide can help prepare the bowel for procedures like colonoscopies. It improves bowel cleanliness, aiding doctors in identifying issues more clearly during exams. One study found that linaclotide increased the detection of polyps, which are growths in the colon that can become cancerous if untreated. This trial will compare linaclotide with a placebo to evaluate its effectiveness in spotting potential problems early, supporting colorectal health. While linaclotide doesn't directly treat colorectal cancer, it shows promise in assisting with procedures related to colorectal health. ^{3 6 7 8 9}

Who Is on the Research Team?

Scott Waldman, MD

Principal Investigator

Sidney Kimmel Cancer Center at Thomas Jefferson University

Are You a Good Fit for This Trial?

This trial is for individuals with stages 0-3 colorectal cancer or those who've had colorectal adenomas. Participants must be able to swallow capsules, sign consent forms, maintain pill diaries, and use effective contraception if of childbearing potential. Exclusions include certain digestive diseases, recent linaclotide use, other cancers treated within the last 6 months (except some skin cancers), current participation in other trials or severe health issues.

Inclusion Criteria

You can easily swallow capsules without any problems.

Participants must have no chronic, clinically severe health issues which, in the opinion of their physician or the research team, could preclude trial activities including the one week drug exposure phase

Ability to maintain pill diaries

Exclusion Criteria

Pregnant or lactating women

I have a history of bleeding problems but can use NSAIDs like aspirin.

I have taken linaclotide in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive linaclotide or placebo orally daily for 7 days and undergo standard of care colonoscopy or surgery on day 7

1 week

1 visit (in-person) for colonoscopy or surgery

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

1 visit (in-person) on day 14

Long-term follow-up

Participants are monitored for secondary outcomes and adverse events

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Linaclotide

Trial Overview

The study is testing how well linaclotide works for patients with early-stage colorectal cancer by comparing it to a placebo. Linaclotide is a small protein that encourages intestinal cells to release water and salt. The trial will see if this treatment can benefit patients awaiting surgery.

How Is the Trial Designed?

Group I: Arm I (linaclotide) Experimental Treatment 1 Intervention

Patients receive linaclotide PO daily on days 1-7 and undergo standard of care colonoscopy or surgery on day 7.

Group II: Arm II (placebo) Placebo Group 1 Intervention

Patients receive placebo PO QD on days 1-7 and undergo standard of care colonoscopy or surgery on day 7.

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

Approved in United States as Linzess for:

• Chronic idiopathic constipation
• Irritable bowel syndrome with constipation (IBS-C)
• Functional constipation in pediatric patients 6 to 17 years of age

Approved in European Union as Constella for:

• Chronic idiopathic constipation
• Irritable bowel syndrome with constipation (IBS-C)

Approved in Canada as Linzess for:

• Chronic idiopathic constipation
• Irritable bowel syndrome with constipation (IBS-C)
• Functional constipation in pediatric patients 6 to 17 years of age

Who Is Running the Clinical Trial?

Sidney Kimmel Cancer Center at Thomas Jefferson University

Lead Sponsor

Trials

164

Recruited

10,900+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

The combination of fluorouracil (5-FU)/leucovorin and irinotecan (CPT-11) has significantly improved response rates and survival times for patients with metastatic colorectal cancer, making it a recommended first-line treatment.

Ongoing randomized phase III trials in Europe are investigating the efficacy of this combination as adjuvant chemotherapy for patients with stage II or III colorectal cancer, aiming to enhance cure rates in those with resected, locally advanced, nonmetastatic disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on European adjuvant trials with irinotecan for colorectal cancer. Douillard, JY., Barbarot, V., Bennouna, J.[2018]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5758862/

Bioactivity of oral linaclotide in human colorectum for ...

Here, we demonstrate that administration of 0.87 milligrams of oral linaclotide daily for 7 days to healthy volunteers, after oral colon ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12174239/

a network meta-analysis of 14 randomized controlled trials

Outcomes (O): the primary outcomes included adequate bowel preparation (success rate) and the total Boston Bowel Preparation Scale (BBPS) score.

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01950403?term=AREA%5BBasicSearch%5D(Linaclotide)&rank=1

Linaclotide Acetate in Preventing Colorectal Cancer ...

This randomized phase I trial studies the side effects and best dose of linaclotide acetate in preventing colorectal cancer in healthy volunteers.

4.

journals.lww.com

journals.lww.com/ajg/fulltext/9900/effect_of_3_day_linaclotide_administration_to.1765.aspx

Effect of 3-day linaclotide administration to reduce the PEG...

Several studies have investigated the role of linaclotide in bowel preparation and have shown its efficacy in reducing PEG intake.

5.

onlinelibrary.wiley.com

onlinelibrary.wiley.com/doi/10.1111/1751-2980.70008

Efficacy and Safety of Linaclotide as an Adjunct ...

Polyp detection rate improved significantly in the 3-L PEG plus linaclotide subgroup (RR 1.78, 95% CI 1.32–2.40), whereas adenoma detection rate ...

6.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK578208/

Linaclotide - StatPearls - NCBI Bookshelf

Geriatric patients: Clinical trials revealed that linaclotide is safe and effective in geriatric patients. The incidence of diarrhea might ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03796884

Linaclotide in Treating Patients With Stages 0-3 Colorectal ...

To confirm the safety and tolerability of linaclotide in sporadic adenoma and cancer patients. TRANSLATIONAL OBJECTIVE: I. To assess the pharmacodynamic ...

8.

e-ce.org

e-ce.org/journal/view.php?number=8042

a grade-assessed systematic review and meta-analysis

Our results suggest that the addition of linaclotide may specifically improve the detection of precancerous polyps. Since the risk of cancer is ...

9.

link.springer.com

link.springer.com/article/10.1007/s00384-025-04931-9

a network meta-analysis of 14 randomized controlled trials

Our objective is to evaluate whether Lin-based regimens offer improved outcomes in bowel cleansing while maintaining safety and tolerability.