Clinical Trials /

A Study of Niclosamide in Patients With Resectable Colon Cancer

NCT02687009

Description:

This study evaluates the safety of Niclosamide in patients with colon cancer that are undergoing primary resection of their tumor. This is a phase I study with three dosage levels to determine the maximum tolerated dose (MTD).

Related Conditions:
  • Colon Adenocarcinoma
  • Rectal Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of Niclosamide in Patients With Resectable Colon Cancer
  • Official Title: A Phase I Study of Niclosamide in Patients With Resectable Colon Cancer

Clinical Trial IDs

  • ORG STUDY ID: Pro00066964
  • NCT ID: NCT02687009

Conditions

  • Colon Cancer

Interventions

DrugSynonymsArms
NiclosamideYomensanNiclosamide

Purpose

This study evaluates the safety of Niclosamide in patients with colon cancer that are undergoing primary resection of their tumor. This is a phase I study with three dosage levels to determine the maximum tolerated dose (MTD).

Detailed Description

      Niclosamide is a drug traditionally used in parasitic infections that has recently been
      shown to regulated the Wnt signaling pathway in cells at the level of the Frizzled receptor.

      The Wnt pathway is critical for embryogenesis, differentiation of progenitor cells, and
      supports proliferation of neoplastic tissue. In cancer, activation of the Wnt pathway leads
      to increased transcription of genes important for growth, proliferation, differentiation,
      apoptosis, genetic stability, migration, and angiogenesis. The Wnt pathway has particular
      importance in colorectal cancer.

      The purpose of this study is to obtain safety data along with pharmacokinetic data and
      information on the changes in the WNT pathway signalling following niclosamide
      administration in humans. This phase I study will support future studies in patients with
      more advanced cancer and other cancers with dysregulation of the Wnt pathway.
    

Trial Arms

NameTypeDescriptionInterventions
NiclosamideExperimental
  • Niclosamide

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of colon adenocarcinoma with a plan to undergo
             surgical resection no sooner than 7 days from the projected date of study drug
             initiation. Patients with rectal cancer not receiving pre-operative chemoradiotherapy
             are also eligible.

          -  Karnofsky performance status greater than or equal to 70%

          -  Age ≥ 18 years.

          -  Adequate hematologic function, with ANC > 1500/microliter, hemoglobin ≥ 9 g/dL (may
             transfuse or use erythropoietin to achieve this level), platelets ≥
             100,000/microliter; INR <1.5, PTT <1.5X ULN

          -  Adequate renal and hepatic function, with serum creatinine < 1.5 mg/dL, bilirubin <
             1.5 mg/dL (except for Gilbert's syndrome which will allow bilirubin ≤ 2.0 mg/dL), ALT
             and AST ≤ 2.5 x upper limit of normal.

          -  Ability to understand and provide signed informed consent that fulfills Institutional
             Review Board's guidelines.

          -  Ability to return to Duke University Medical Center for adequate follow-up, as
             required by this protocol.

        Exclusion Criteria:

          -  Patients with concurrent cytotoxic chemotherapy or radiation therapy are excluded

          -  Known active brain or leptomeningeal metastases (defined as symptomatic metastases)
             or continued requirement for glucocorticoids for brain or leptomeningeal metastases.
             Treated, asymptomatic metastases are permitted provided the patient has been off
             steroids for at least 1 month prior to day 1 of study drug.

          -  Patients with serious intercurrent chronic or acute illness, such as cardiac disease
             (NYHA class III or IV), hepatic disease, or other illness considered by the Principal
             Investigator as unwarranted high risk for investigational drug treatment.

          -  Patients with a medical or psychological impediment to probable compliance with the
             protocol should be excluded.

          -  Concurrent (or within the last 5 years) second malignancy other than non melanoma
             skin cancer, cervical carcinoma in situ, controlled superficial bladder cancer, or
             other carcinoma in situ that has been treated.

          -  Presence of a known active acute or chronic infection including: a urinary tract
             infection, HIV or viral hepatitis.

          -  Patients with prior use of niclosamide or allergies to niclosamide will be excluded
             from the protocol.

          -  Concomitant use of strong CYP3A4, CYP 1A2 , or CYP2C9 substrates (See
             http://medicine.iupui.edu/clinpharm/ddis/main-table).

          -  Pregnant and nursing women should be excluded from the protocol since this research
             may have unknown and harmful effects on an unborn child or on young children. If the
             patient is sexually active, the patient must agree to use a medically acceptable form
             of birth control while receiving treatment and for a period of 12 months following
             the last dose of niclosamide. It is not known whether the treatment used in this
             study could affect the sperm and could potentially harm a child that may be fathered
             while on this study.

          -  Patients with complete bowel obstruction or who are at high risk for GI perforation
             or severe hemorrhage. Patients with inflammatory bowel disease.
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose limiting toxicity
Time Frame:5 DAYS
Safety Issue:
Description:The NCI Common Toxicity Criteria version 4.0 will be used to grade adverse events to determine dose limiting toxicity for safety measure

Secondary Outcome Measures

Measure:Niclosamide blood levels
Time Frame:1 DAY
Safety Issue:
Description:
Measure:Niclosamide blood levels
Time Frame:2 days
Safety Issue:
Description:
Measure:Niclosamide blood levels
Time Frame:8 days
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Michael Morse, MD

Trial Keywords

  • colon cancer
  • Wnt pathway
  • Frizzled

Last Updated

April 18, 2017