A Clinical Safety and Efficacy Study of Mebendazole on GI Cancer or Cancer of Unknown Origin.

This study will evaluate the safety and efficacy of mebendazole (ReposMBZ) in patient with advanced gastrointestinal cancer or cancer of unknown origin. All patients will be given ReposMBZ for 16 weeks continuous treatment, individually dosed based on the serum concentration of mebendazole.

Mebendazole has been used extensively during long time for local gut helminthic infections at low dose but also at considerably higher doses during months to years against invasive echinococcus infections. Recent research has now clearly indicated that mebendazole has anticancer effect. Given these observations and the experience of excellent tolerance to mebendazole the current clinical trial protocol is based on the repositioning strategy to more extensively investigate whether mebendazole could be developed into a useful anticancer drug.

Eligibility Criteria:
Inclusion Criteria:

1. At least 18 years of age.
2. Histologically confirmed diagnosis of squamous cell cancer or adenocarcinoma, including primary cancer of the liver, of the gastrointestinal tract or cancer of unknown origin.
3. Measurable disease according to RECIST 1.1.
4. Defined time to tumour progression on the standard/experimental treatment preceding the trial treatment.
5. Locally advanced or metastatic disease not amenable to standard treatment, i.e. progress on standard therapy or observed/expected intolerance to standard therapy.
6. - (removed via Amendment 1)
7. Pharmacological treatment attempt considered reasonable.
8. Females of childbearing potential should use adequate contraception throughout the study;

   1. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal)
   2. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable)
   3. Intrauterine device (IUD)
   4. Intrauterine hormone-releasing system (IUS)
   5. Bilateral tubal occlusion
   6. Vasectomized partner
   7. Sexual abstinence
9. Signed informed consent.

Exclusion Criteria:

1. Anti-tumour therapy within 3 weeks prior to study drug administration day
2. Ongoing infection or other major recent or ongoing disease that, according to the investigator, poses an unacceptable risk to the patient.
3. WHO performance status ≥ 2.
4. Child-Pugh B or C liver function status if hepatocellular carcinoma.
5. Inadequate laboratory parameters reflecting major organ function i.e.:

   1. neutrophils ≤ 1,3 x 109/l
   2. platelets ≤ 100 x 109/l
   3. bilirubin \> 1.5 x upper limit of normal (ULN)
   4. Alanine aminotransferase (ALAT) \> 5 x ULN
   5. Glomerular filtration rate (GFR) \<50 ml/min (calculated from P-creatinine)
   6. Prothrombin complex/INR outside normal range
6. Current active participation in any other interventional clinical study.
7. Contraindications to the investigational product, e.g. known or suspected hypersensitivity or inability to oral drug administration.
8. Pregnancy or lactation.
9. Lack of suitability for participation in the study, e g expected difficulties to follow the protocol procedures, as judged by the Investigator.