Linaclotide for Colorectal Cancer

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

230 Participants Needed

Trial Summary

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.

How does the drug Linaclotide differ from other treatments for colorectal cancer?

Linaclotide is unique for colorectal cancer treatment because it contains linalool, a compound known for its ability to induce cancer cell death (apoptosis) by generating hydroxyl radicals specifically in cancer cells, which is different from traditional chemotherapy drugs like irinotecan that target rapidly dividing cells more broadly. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial studies how well linaclotide works in patients with early-stage colorectal cancer. Linaclotide helps the intestines release water and salt by binding to cell receptors. Researchers want to see if it affects cancer-related markers. Linaclotide is an FDA-approved drug primarily used for treating chronic idiopathic constipation and irritable bowel syndrome with constipation (IBS-C).

Research Team

Scott Waldman, MD

Principal Investigator

Sidney Kimmel Cancer Center at Thomas Jefferson University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

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

Anticancer effect of linalool via cancer-specific hydroxyl radical generation in human colon cancer. [2019]

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

Update on European adjuvant trials with irinotecan for colorectal cancer. [2018]

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

Anticancer activity of linalool: comparative investigation of ultrastructural changes and apoptosis in breast cancer cells. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

Linalool preferentially induces robust apoptosis of a variety of leukemia cells via upregulating p53 and cyclin-dependent kinase inhibitors. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

Levistolide A Induces Apoptosis via ROS-Mediated ER Stress Pathway in Colon Cancer Cells. [2022]