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Linaclotide in Treating Patients With Stages 0-3 Colorectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03796884
Recruitment Status : Recruiting
First Posted : January 8, 2019
Last Update Posted : December 5, 2019
Sponsor:
Collaborator:
United States Department of Defense
Information provided by (Responsible Party):
Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )

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.

Condition or disease Intervention/treatment Phase
Colorectal Adenoma Drug: Linaclotide Other: Placebo Phase 2

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 230 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Phase II Randomized, Placebo-Controlled Trial of Linaclotide to Demonstrate Bioactivity in Patients With Sporadic Colorectal Adenomas and With Colorectal Cancer
Actual Study Start Date : October 30, 2019
Estimated Primary Completion Date : October 1, 2020
Estimated Study Completion Date : October 1, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm I (linaclotide)
Patients receive linaclotide PO daily on days 1-7 and undergo standard of care colonoscopy or surgery on day 8.
Drug: Linaclotide
Given PO
Other Names:
  • 851199-59-2
  • Linzess

Placebo Comparator: Arm II (placebo)
Patients receive placebo PO QD on days 1-7 and undergo standard of care colonoscopy or surgery on day 8.
Other: Placebo
Given PO




Primary Outcome Measures :
  1. Pharmacodynamics effect on cGMP levels [ Time Frame: Up to 2 years ]
    Will compare cGMP levels in adenomas between study arms using a two-sample t-test (alpha=.05; two-sided) or Wilcoxon rank sum test.


Secondary Outcome Measures :
  1. Incidence of adverse events (AEs) [ Time Frame: From day 7 to day 14 ]
    All participants will be evaluated for toxicity from the time of their first dose of linaclotide or placebo. Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be used to summarize adverse events associated with linaclotide.

  2. Ki-67 expression [ Time Frame: Up to 2 years ]
    Wilcoxon rank sum test will be used to compare Ki-67 expression in adenomas across arms.

  3. GUCY2C expression [ Time Frame: Up to 2 years ]
    Wilcoxon rank sum and Fisher's exact tests will be used to compare GUCY2C expression between study arms.

  4. Guanylin levels [ Time Frame: Up to 2 years ]
    Wilcoxon rank sum and Fisher's exact tests will be used to compare guanylin levels between study arms.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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) 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

Exclusion Criteria:

  • History of gastroparesis
  • History of celiac disease
  • Inflammatory bowel disease (Crohn's disease, ulcerative colitis)
  • Microscopic colitis, including collagenous colitis
  • Currently taking or have previously taken Linaclotide
  • 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 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03796884


Contacts
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Contact: Scott Waldman, MD 215-955-6086 scott.waldman@jefferson.edu

Locations
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United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: David Weinberg, MD       david.weinberg@fccc.edu   
Sidney Kimmel Cancer Center at Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19126
United States, Washington
VA Puget Sound Health Care Sysem Not yet recruiting
Seattle, Washington, United States, 98108
Contact: Jason Dominitz, MD       jason.dominitz@va.gov   
Sponsors and Collaborators
Sidney Kimmel Cancer Center at Thomas Jefferson University
United States Department of Defense
Investigators
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Principal Investigator: Scott Waldman, MD Sidney Kimmel Cancer Center at Thomas Jefferson University
Additional Information:
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Responsible Party: Sidney Kimmel Cancer Center at Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT03796884    
Other Study ID Numbers: 18F.524
First Posted: January 8, 2019    Key Record Dates
Last Update Posted: December 5, 2019
Last Verified: December 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Adenoma
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Linaclotide
Guanylyl Cyclase C Agonists
Enzyme Activators
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Agents