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 2026-10-08.
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.
6,541 studies on the registry are indexed under Colorectal Neoplasms; 1,667 are open to participants now.
This study's enrollment of 150 is above the median of 76 across 4,800 interventional studies indexed under Colorectal Neoplasms.
Browse Colorectal Neoplasms studies →Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University is the lead sponsor of 41 studies on the registry; 3 are open to participants now.
Of its 17 completed or terminated interventional studies of FDA-regulated products, 14 (82%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Washout period
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is active, not recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Linaclotide
Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University