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

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.

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

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