Squamous cell cancer or adenocarcinoma, including primary cancer of the liver, of the gastrointestinal tract or cancer of unknown origin MedDRA version: 20.0 Level: LLT Classification code 10017985 Term: Gastrointestinal neoplasm malignant System Organ Class: 100000004864
Conditions
Interventions
Product Name: Repos MBZ
Pharmaceutical Form: Capsule
INN or Proposed INN: MEBENDAZOLE
CAS Number: 31431-39-7
Current Sponsor code: Repos MBZ
Concentration unit: mg milligram(s)
Concentration type: ran
Sponsors
ReposPharma
Eligibility
Sex/Gender
All
Inclusion 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. - 7. Pharmacological treatment attempt considered reasonable. 8. Females of childbearing potential should use adequate contraception throughout the study; a. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal) b. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable) c. Intrauterine device (IUD) d. Intrauterine hormone-releasing system (IUS) e. Bilateral tubal occlusion f. Vasectomized partner g. Sexual abstinence 9. Signed informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. Anti-tumour therapy within 3 weeks prior to study drug administration day 1. 2. Ongoing infection or other major recent or ongoing disease that, according to the Investigator’s assessment, 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.: a. neutrophils = 1,3 x 109/l b. platelets = 100 x 109/l c. bilirubin > 1.5 x ULN d. ALAT > 5 x ULN e. GFR <50 ml/min (calculated from P-creatinine) f. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: · Safety profile of Repos MBZ. · Anti-tumour efficacy: tumour response rate and prolongation of time to tumour progression (TTP) according to RECIST 1.1.;Secondary Objective: · The single dose pharmacokinetic (PK) profile of Repos MBZ. · The steady state PK profile of Repos MBZ. · Repos MBZ induced changes in blood cytokines and immune cells. · Overall survival. · Change in tumour load and TTP according to irRECIST;Primary end point(s): Safety: · Number of AEs probably or possibly related to the study drug, graded according to CTCAE 4.03 · Changes in lab parameters and vital sign over time vs baseline Efficacy: · Best overall radiological response according to RECIST 1.1. · Time to tumour progression on Repos MBZ compared with time to progression on the treatment just preceding participation in this protocol.;Timepoint(s) of evaluation of this end point: Safety: Continuously during treatment and up to 0-30 days after treatment stop. Efficacy: Every 8 weeks during study / until progress. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): · Cmax, Tmax and T1/2 after single dose Repos MBZ. · Number of patients that reach the steady state S-mebendazole target concentration of 300 ng/ml (accepted range 250 – 350 ng/ml), time to reach this concentration and S-mebendazole concentration variation over time. · Immunological changes induced by mebendazole from baseline, as reflected in cytokines and immune cells in blood · Overall survival from start of treatment phase to death from any cause. · Best overall radiological response according to irRECIST 1.1. ;Timepoint(s) of evaluation of this end point: PK-parameters will be assesed weekly until target concentration is reached . Then PK will be assessed every 4 weeks. Survival will be followed up until time to death. | — |
Countries
Sweden
Contacts
Public ContactMårten Fryknäs
ReposPharma
Outcome results
None listed