Table 1 Nikolo trial inclusion and exclusion criteria

Inclusion criteria

 Disease related

  Patients with metachronous or synchronous metastases of a colorectal cancer progressing under standard therapy

  No proven brain metastases

  No curative option available

  No standard therapy available

  At least one metastasis has to be measurable according to RECIST V 1.1 in X-ray computed tomography or magnetic resonance imaging (not older than 2 weeks before inclusion into the trial)

 Demographic

  Age > 18 years

  Eastern Cooperative Oncology Group performance status ECOG 0–1

 Laboratory

  Absolute neutrophil count ≥ 1.5 × 10⁹/ L

  Platelet count ≥ 100 × 10⁹/L

  Leukocytes ≥ 1.0 × 10⁹/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

  AST ≤ 2.5xULN in patients without liver metastases or ≤ 5.0xULN in patients with liver metastases

  ALT ≤ 2.5xULN in patients without liver metastases or < 5.0xULN in patients with liver metastases

  Adequate renal function (creatinine ≤ 1.5xULN)

 Ethical/Other

  Electrocardiography without clinical significant abnormalities

  Written informed consent before inclusion according to the ICH-GCP and national/local regulations

  Patients should use adequate birth control measures, during the study treatment period and for at least 3 months after the last study treatment

  Women of childbearing potential need to have a negative pregnancy test 72 h before the application of the first dose of niclosamide

  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

Exclusion criteria

 Concurrent conditions

  Pregnant or lactating females

  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

  Clinical significant heart disease like e.g. uncontrolled blood pressure; heart failure NYHA grade > 2; cardiac infarction within the last 12 months

  Known uncontrolled concomitant disease despite treatment like e.g. chronic obstructive pulmonary disease

  Known alcohol or drug abuse

  Serious infection

  Any psychological, familial, sociological or geographical condition, potentially hampering compliance with the study protocol and follow-up schedule

 Ethical/Other

  Participation in another interventional study within the last 30 days

  Known hypersensitivity against a part of the study drug

  Life expectancy < 3 months

  Human immunodeficiency virus infection or active hepatitis B/C

  Patients that are committed to an institution by official or judicial order

  Persons that are depending on the sponsor, investigator or deputy