Linaclotide in Treating Patients With Stages 0-3 Colorectal Cancer

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.

II. To confirm the safety and tolerability of linaclotide in sporadic adenoma and cancer
patients.

Inclusion Criteria:

- 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)

- 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

Exclusion Criteria:

- History of gastroparesis

- History of celiac disease

- Inflammatory bowel disease (Crohn's disease, ulcerative colitis)

- Microscopic colitis, including collagenous colitis

- Any malignancy within 3 years of baseline except colorectal cancer. 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 competing clinical trials

- 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

- Chronic use of anti-coagulants or non-NSAID anti-platelet agents will serve as an
exclusion only when such medications cannot be safely discontinued before study
related endoscopy or surgery