Clinical Trials /

Linaclotide in Treating Patients With Stages 0-3 Colorectal Cancer

NCT03796884

Description:

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.

Related Conditions:
  • Colorectal Adenoma
  • Colorectal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Linaclotide in Treating Patients With Stages 0-3 Colorectal Cancer
  • Official Title: Phase II Randomized, Placebo-Controlled Trial of Linaclotide to Demonstrate Bioactivity in Patients With Sporadic Colorectal Adenomas and With Colorectal Cancer

Clinical Trial IDs

  • ORG STUDY ID: 18F.524
  • NCT ID: NCT03796884

Conditions

  • Colorectal Adenoma

Interventions

DrugSynonymsArms
Linaclotide851199-59-2, LinzessArm I (linaclotide)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (linaclotide)ExperimentalPatients receive linaclotide PO daily on days 1-7 and undergo standard of care colonoscopy or surgery on day 8.
  • Linaclotide
Arm II (placebo)Placebo ComparatorPatients receive placebo PO QD on days 1-7 and undergo standard of care colonoscopy or surgery on day 8.

    Eligibility 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
          
    Maximum Eligible Age:70 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:Female
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Pharmacodynamics effect on cGMP levels
    Time Frame:Up to 2 years
    Safety Issue:
    Description: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

    Measure:Incidence of adverse events (AEs)
    Time Frame:From day 7 to day 14
    Safety Issue:
    Description: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.
    Measure:Ki-67 expression
    Time Frame:Up to 2 years
    Safety Issue:
    Description:Wilcoxon rank sum test will be used to compare Ki-67 expression in adenomas across arms.
    Measure:GUCY2C expression
    Time Frame:Up to 2 years
    Safety Issue:
    Description:Wilcoxon rank sum and Fisher's exact tests will be used to compare GUCY2C expression between study arms.
    Measure:Guanylin levels
    Time Frame:Up to 2 years
    Safety Issue:
    Description:Wilcoxon rank sum and Fisher's exact tests will be used to compare guanylin levels between study arms.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Sidney Kimmel Cancer Center at Thomas Jefferson University

    Last Updated

    December 4, 2019