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A Study of Niclosamide in Patients With Resectable Colon 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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02687009
Recruitment Status : Terminated (low accrual)
First Posted : February 22, 2016
Last Update Posted : February 19, 2020
Sponsor:
Information provided by (Responsible Party):
Michael Morse, MD, Duke University

Tracking Information
First Submitted Date  ICMJE February 10, 2016
First Posted Date  ICMJE February 22, 2016
Last Update Posted Date February 19, 2020
Actual Study Start Date  ICMJE November 7, 2017
Actual Primary Completion Date December 12, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 16, 2016)
  • Dose limiting toxicity [ Time Frame: 5 DAYS ]
    The NCI Common Toxicity Criteria version 4.0 will be used to grade adverse events to determine dose limiting toxicity for safety measure
  • Dose limiting toxicity [ Time Frame: 30 DAYS ]
    he NCI Common Toxicity Criteria version 4.0 will be used to grade adverse events to determine dose limiting toxicity for safety measure
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 16, 2016)
  • Niclosamide blood levels [ Time Frame: 1 DAY ]
  • Niclosamide blood levels [ Time Frame: 2 days ]
  • Niclosamide blood levels [ Time Frame: 8 days ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Niclosamide in Patients With Resectable Colon Cancer
Official Title  ICMJE A Phase I Study of Niclosamide in Patients With Resectable Colon Cancer
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Colon Cancer
Intervention  ICMJE Drug: Niclosamide
Niclosamide will be taken orally in the morning of each day from day 1-7 prior to surgery for resection of primary tumor. Niclosamide tablets must be chewed well prior to swallowing.
Other Name: Yomensan
Study Arms  ICMJE Experimental: Niclosamide
Intervention: Drug: Niclosamide
Publications * Osada T, Chen M, Yang XY, Spasojevic I, Vandeusen JB, Hsu D, Clary BM, Clay TM, Chen W, Morse MA, Lyerly HK. Antihelminth compound niclosamide downregulates Wnt signaling and elicits antitumor responses in tumors with activating APC mutations. Cancer Res. 2011 Jun 15;71(12):4172-82. doi: 10.1158/0008-5472.CAN-10-3978. Epub 2011 Apr 29.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: February 17, 2020)
1
Original Estimated Enrollment  ICMJE
 (submitted: February 16, 2016)
18
Actual Study Completion Date  ICMJE December 12, 2017
Actual Primary Completion Date December 12, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02687009
Other Study ID Numbers  ICMJE Pro00066964
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Michael Morse, MD, Duke University
Study Sponsor  ICMJE Michael Morse, MD
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Duke University
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP