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

Phase 2

• Conditions: Colorectal Cancer
• Interventions: Drug: Niclosamide

• Registration Number: NCT02519582
• Lead Sponsor: Charite University, Berlin, Germany

Brief Summary

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.

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 Timeline

• Study First Submitted: 2015-07-30
• Study Start: 2015-08
• Study First Submitted QC: 2015-08-06
• Study First Posted: 2015-08-11
• Status Verified: 2018-09
• Last Update Submitted: 2018-09-11
• Last Update Posted: 2018-09-12
• Primary Completion: 2019-12
• Study Completion: 2020-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 37

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Niclosamid	Niclosamide	Patients receive 2 g niclosamide orally per day until progression or toxicity

Primary Outcome Measures

Name	Time	Method
Progression free survival	At 4 months	defined as the time from patient inclusion to the date of progression

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Charité Universitätsmedizin Berlin; Charité Comprehensive Cancer Center; 🇩🇪 Berlin, Germany