Drug Trial to Investigate the Safety and Efficacy of Niclosamide Tablets in Patients With Metastases of a Colorectal Cancer Progressing After Therapy (Nikolo)

Phase II Trial to Investigate the Safety and Efficacy of Orally Applied Niclosamide in Patients With Metachronous or Synchronous Metastases of a Colorectal Cancer Progressing After Therapy

Phase II trial evaluating the safety and efficacy of oral appliqued niclosamide in patients who are progressive with metachronous or synchronous metastases of colorectal cancer among the previous therapy (Nikolo). Monocentric open-label clinical trial of phase II. All patients received 2 g p.o. niclosamide daily until progression (according to RECIST) or unacceptable toxicity or discontinuation of study for other reasons.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Niclosamide

Detailed Description

Effectiveness:

• effectiveness is measured by progression-free survival evaluated by RECIST (Response Evaluation Criteria In Solid tumor).

Overall survival For overall survival, the curves are estimated using the Kaplan-Meier method

• Study Type: Interventional
• Enrollment (Anticipated): 37
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Susen Burock; Phone Number: 0049 (0)30450564648; Email: susen.burock@charite.de

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Recruiting
    • Charité Universitätsmedizin Berlin; Charité Comprehensive Cancer Center
    • Contact: Susen Burock; Phone Number: 0049(0)30450564648; Email: susen.burock@charite.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient with metachronous or synchronous metastases of a colorectal cancer progression under standard therapy
• no proven brain metastases
• no curative option
• no standard therapy available
• Age > 18 years
• At least one metastases measurable according to Response Evaluation Criteria In Solid Tumors V 1.1 in CT or MRI scan not older than 2 weeks before inclusion into the trial
• Lab values within the usual borders for these patient group e.g.
• Neutrophil ≥ 1.5x109/ •Platelets ≥ 100x109/L
• Leukocytes ≥ 1.0x109/L
• Hemoglobin ≥ 9.0 g/dL or 5.59 mmol/l
• Bilirubin ≤ 2 x Upper Limit of Normal (ULN) if not due to Gilbert's syndrome
• Aspartate Aminotransferase ≤ 2.5x Upper Limit of Normal in patients without liver metastases or ≤ 5.0x Upper Limit of Normal in patients with liver metastases
• Alanine aminotransferase ≤ 2.5x Upper Limit of Normal in patients without liver metastases < 5.0 x Upper Limit of Normal in patients with liver metastases
• adequate renal function (creatinin ≤ 1.5x Upper Limit of Normal)
• Eastern Cooperative Oncology Group 0 - 1
• EKG without clinical significant abnormalities
• No other malignant disease (except colorectal cancer) within the last 5 years before inclusion in the trial except adequately treated basal cell carcinoma of the skin or squamous cell carcinoma of the skin, in situ carcinoma of the cervix. Patients with a malignant disease in history have to be free of disease for 5 years.
• No clinical significant heart disease like e.g.
• Uncontrolled blood pressure
• Heart failure New York Heart Association grade > 2
• Cardiac infarction within the last 12 months
• No known uncontrolled concomitant disease despite treatment like e.g.
• Chronic obstructive pulmonary disease (COPD)
• Serious infections
• No known alcohol or drug abuses
• Absence of any psychological, familial, sociological or geographical condition, potentially hampering compliance with the study protocol and follow-up schedule
• Patients should use adequate birth control measures, during the study treatment period and for at least 3 months after the last study treatment.
• For women of childbearing potential (WOCBP):negative pregnancy test 72 hours before the application of the first dose if the study drug
• Patients who are breastfeeding must stop breastfeeding before the first dose of the study drug and not restart till 8 week after the last drug intake.
• Written informed consent before inclusion according to the International Conference on Harmonisation good clinical practice (ICH GCP) and national/local regulations

Exclusion Criteria:

• Life expectancy < 3 months
• Participation in another interventional study within the last 30 days
• Known hypersensitivity against a part of the study drug
• Pregnancy or breastfeeding
• HIV infection oder active hepatitis B/C

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Niclosamid; Patients receive 2 g niclosamide orally per day until progression or toxicity	Drug: Niclosamide; 2 g per day orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	defined as the time from patient inclusion to the date of progression	At 4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	defined as the time from patient inclusion to the date of death or date of last follow-up news (censured data)	From date of randomization until the date of death, assessed up to 2 years
Time to progression	Progression according to RECIST	From date of randomization until the date of first documented progression, assessed up to 2 years
Disease control rate	remission + partial remission + stable disease	From date of randomization, assessed up to 2 years
Number of Adverse Events > grade 2 toxicities according to NCI Common Toxicity Criteria for Adverse Effects v 4.03	number of adverse events > grade 2 toxicities according to NCI Common Toxicity Criteria for Adverse Effects v 4.03	From date of randomization, assessed up to 1 months after end ot therapy
Number of Serious Adverse Events	number of serious adverse events	From date of randomization, assessed up to 1 months after end ot therapy

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: Center for Molecular Medicine

Publications and helpful links

General Publications

• Burock S, Daum S, Keilholz U, Neumann K, Walther W, Stein U. Phase II trial to investigate the safety and efficacy of orally applied niclosamide in patients with metachronous or sychronous metastases of a colorectal cancer progressing after therapy: the NIKOLO trial. BMC Cancer. 2018 Mar 15;18(1):297. doi: 10.1186/s12885-018-4197-9.

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): August 1, 2020

Study Registration Dates

• First Submitted: July 30, 2015
• First Submitted That Met QC Criteria: August 6, 2015
• First Posted (Estimate): August 11, 2015

Study Record Updates

• Last Update Posted (Actual): September 12, 2018
• Last Update Submitted That Met QC Criteria: September 11, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Colorectal Cancer; S100A4
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Anti-Infective Agents; Antiparasitic Agents; Antinematodal Agents; Anthelmintics; Antiplatyhelmintic Agents; Anticestodal Agents; Niclosamide
• Other Study ID Numbers: CCCC-mCRC-01