A Phase 2 interventional study of Linaclotide and Placebo in Colorectal Adenoma, Stage 0 Colorectal Cancer AJCC v8 and Stage I Colorectal Cancer AJCC v8, sponsored by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University. Active, not recruiting at 3 sites in United States. Open to female participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-07-22.
Sponsored by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University · Phase 2, Interventional, and Treatment
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.
PRIMARY OBJECTIVES:
I. To determine whether, compared to placebo, linaclotide administered as a single oral daily dose x 7 days, induces a pharmacodynamics (PD) effect on cGMP levels, based on biopsy samples of adenomas or resected colorectal adenocarcinomas.
SECONDARY OBJECTIVES:
I. To compare Ki-67, guanylin levels and GUCY2C expression in adenomas and cancers versus normal tissue after exposure to linaclotide or placebo.
II. To confirm the safety and tolerability of linaclotide in sporadic adenoma and cancer patients.
TRANSLATIONAL OBJECTIVE:
I. To assess the pharmacodynamic effect of linaclotide on pathway-specific biomarkers relevant to GUCY2C signaling (i.e. VASP phosphorylation), markers of mutant APC-beta-catenin signaling (beta-catenin levels, beta-catenin nuclear localization, axin levels, c-Myc levels, guanylin levels, PCNA expression), based on adenoma/cancer and normal mucosa biopsy samples obtained by endoscopy following linaclotide or placebo exposure.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive linaclotide orally (PO) daily on days 1-7 and undergo standard of care colonoscopy or surgery on day 7.
ARM II. Patients receive placebo PO QD on days 1-7 and undergo standard of care colonoscopy or surgery on day 7.
After completion of study treatment, patients are followed up at day 14.
Exclusion Criteria:
Patients receive linaclotide PO daily on days 1-7 and undergo standard of care colonoscopy or surgery on day 7.
Drug: Linaclotide
Patients receive placebo PO QD on days 1-7 and undergo standard of care colonoscopy or surgery on day 7.
Other: Placebo
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
Given PO
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.
Time frame: Up to 2 years, plus an additional 12 months for primary analysis
Incidence of adverse events (AEs)
All participants will be evaluated for toxicity. Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be used to summarize adverse events associated with linaclotide.
Time frame: 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
Wilcoxon rank sum test will be used to compare Ki-67 expression in adenomas across arms.
Time frame: Up to 2 years
GUCY2C expression
Wilcoxon rank sum and Fisher's exact tests will be used to compare GUCY2C expression between study arms.
Time frame: Up to 2 years
Guanylin levels
Wilcoxon rank sum and Fisher's exact tests will be used to compare guanylin levels between study arms.
Time frame: Up to 2 years
VASP serine 239 phosphorylation
Assessed by immunoblot analysis. Wilcoxon rank sum and Fisher's exact tests will be used to compare VASP phosphorylation between study arms.
Time frame: Up to 2 years
Beta-catenin levels
Assessed by immunoblot analysis. Wilcoxon rank sum and Fisher's exact tests will be used to compare beta-catenin accumulation and downstream signaling between study arms.
Time frame: Up to 2 years
Beta-catenin nuclear localization
Assessed by immunofluorescence. Wilcoxon rank sum and Fisher's exact tests will be used to compare beta-catenin accumulation and downstream signaling between study arms
Time frame: Up to 2 years
Axin and c-Myc messenger ribonucleic acid (mRNA) levels
Assessed by quantitative reverse transcriptase-polymerase chain reaction. Wilcoxon rank sum and Fisher's exact tests will be used to compare axin and c-Myc mRNA levels between study arms.
Time frame: Up to 2 years
PCNA expression
Assessed by immunofluorescence.
Time frame: Up to 2 years
This study is active, not recruiting, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
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Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University