Linaclotide in Treating Patients With Stages 0-3 Colorectal Cancer

NCT03796884 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 18F.524CDMRP-CA170223JT 13271
• Study Type: interventional
• Target: 230
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial studies the how well linaclotide works in treating patients with stages 0-3 colorectal cancer. Linaclotide is a very small protein that binds to receptors on intestinal cells and makes them secrete water and salt.

Conditions

Colorectal Adenoma; Stage 0 Colorectal Cancer AJCC v8; Stage I Colorectal Cancer AJCC v8; Stage II Colorectal Cancer AJCC v8; Stage IIA Colorectal Cancer AJCC v8; Stage IIB Colorectal Cancer AJCC v8; Stage IIC Colorectal Cancer AJCC v8; Stage III Colorectal Cancer AJCC v8; Stage IIIA Colorectal Cancer AJCC v8; Stage IIIB Colorectal Cancer AJCC v8; Stage IIIC Colorectal Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Pharmacodynamics effect on cGMP levels

  Will compare cGMP levels in adenomas between study arms using a two-sample t-test (alpha=.05; two-sided) or Wilcoxon rank sum test.

  Up to 2 years, plus an additional 12 months for primary analysis

Secondary Outcomes (4)

• Incidence of adverse events (AEs)

  From the time of first dose of linaclotide or placebo until resolution, if related to linaclotide, or through 30 days after occurrence

• Ki-67 expression

  Up to 2 years

• GUCY2C expression

  Up to 2 years

• Guanylin levels

  Up to 2 years

Other Outcomes (5)

• VASP serine 239 phosphorylation

  Up to 2 years

• Beta-catenin levels

  Up to 2 years

• Beta-catenin nuclear localization

  Up to 2 years

Study Arms (2)

Arm I (linaclotide)

EXPERIMENTAL

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

Drug: Linaclotide

Arm II (placebo)

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Linaclotide DRUG

Given PO

Also known as: 851199-59-2, Linzess, [9-L-tyrosine]heat-stable enterotoxin (Escherichia coli)-(6-19)-peptide, L-Tyrosine, L-cysteinyl-L-cysteinyl-L-alpha-glutamyl-L-tyrosyl-L-cysteinyl-L-cysteinyl-L- asparaginyl-L-prolyl-L-alanyl-L-cysteinyl-L-threonylglycyl-L-cysteiny, cyclic (1->6), (2->10), (5->13)-tris(disulfide), MD-1100

Arm I (linaclotide)

Placebo OTHER

Given PO

Arm II (placebo)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• History of 1 or more sporadic colorectal adenoma on previous endoscopy (adenoma cohort) or stage 0-3 biopsy proven colorectal cancer (CRC) (colorectal cancer cohort) who are scheduled for a surgical procedure
• Ability to understand and willingness to sign a written informed consent document and follow study procedures
• Ability to swallow capsules without difficulty
• Ability to maintain pill diaries
• Willingness to employ adequate contraception for men and women of childbearing potential for the duration of the study. Acceptable methods include double barrier methods, intrauterine device (IUD), postmenopausal status, and/or documentation of surgical sterilization
• 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

You may not qualify if:

• History of gastroparesis
• History of celiac disease
• Inflammatory bowel disease (Crohn's disease, ulcerative colitis)
• Microscopic colitis, including collagenous colitis
• Has taken linaclotide within 30 days prior to consent
• Any malignancy except colorectal cancer or any active radiotherapy or cytotoxic chemotherapy within the last 6 months of baseline. Participants with a history of basal cell or squamous cell skin cancer may be enrolled at the discretion of the investigator
• Participants may not be receiving any other investigational agents, or be active participants in any clinical trials. If participants previously participated in a clinical trial, a 30 day washout period for the investigational drug is needed before the participant can be considered for this study
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to linaclotide
• Uncontrolled current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or lactating women
• History of bleeding/coagulation problems. Concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin is acceptable
• Any medical condition judged by the investigator to constitute a risk to safe participation
• At risk for obstructing or near-obstructing mechanical gastrointestinal obstruction

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University: lead
• United States Department of Defense: collaborator

Study Sites (3)

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19126, United States

Location

VA Puget Sound Health Care Sysem

Seattle, Washington, 98108, United States

Location

Related Links

• Thomas Jefferson University Hospital

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

linaclotide; Tyrosine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Scott Waldman, MD

  Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 7, 2019
• First Posted: January 8, 2019
• Study Start: October 30, 2019
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: April 2, 2026

Record last verified: 2026-03

Locations

US (3)