A Study of Niclosamide in Patients With Resectable Colon Cancer

NCT02687009 | Terminated Phase 1 FDA Drug

• 1 other identifier: Pro00066964
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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).

Conditions

Colon Cancer

Keywords

colon cancer; Wnt pathway; Frizzled

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicity

  The NCI Common Toxicity Criteria version 4.0 will be used to grade adverse events to determine dose limiting toxicity for safety measure

  5 DAYS

• Dose limiting toxicity

  he NCI Common Toxicity Criteria version 4.0 will be used to grade adverse events to determine dose limiting toxicity for safety measure

  30 DAYS

Secondary Outcomes (3)

• Niclosamide blood levels

  1 DAY

• Niclosamide blood levels

  2 days

• Niclosamide blood levels

  8 days

Study Arms (1)

Niclosamide

EXPERIMENTAL

Drug: Niclosamide

Interventions

Niclosamide DRUG

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.

Also known as: Yomensan

Niclosamide

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Michael Morse, MD: lead

Study Sites (1)

Duke University

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• 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.

  PMID: 21531761 BACKGROUND

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Niclosamide

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Salicylanilides; Anilides; Amides; Organic Chemicals; Salicylamides; Aniline Compounds; Amines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 10, 2016
• First Posted: February 22, 2016
• Study Start: November 7, 2017
• Primary Completion: December 12, 2017
• Study Completion: December 12, 2017
• Last Updated: February 19, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)