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

NCT03628079 | Terminated Phase 1 DMC

• 1 other identifier: RP-2017-001
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cancer of the Gastrointestinal Tract; Cancer of Unknown Origin

Outcome Measures

Primary Outcomes (14)

• Incidence of adverse events (AEs) probably or possibly related to ReposMBZ

  AEs graded according to CTCAE 4.03.

  From date of first dose, up to 30 days after last dose of ReposMBZ or start of new treatment, whatever comes first, assessed up to 20 weeks after start of treatment phase.

• Changes in plasma Albumin over time

  Blood Chemistry (plasma): Albumin (g/L)

  From date of first dose, up to 30 days after last dose of ReposMBZ or start of new treatment, whatever comes first, assessed up to 20 weeks after start of treatment phase.

• Changes in C-reactive protein (CRP) over time

  Blood chemistry (plasma): CRP (mg/L)

  From date of first dose, up to 30 days after last dose of ReposMBZ or start of new treatment, whatever comes first, assessed up to 20 weeks after start of treatment phase.

• Changes in plasma Sodium, Potassium, Calcium and Glucose over time

  Blood chemistry (plasma): Sodium, Potassium, Calcium, Glucose (mmol/L)

  From date of first dose, up to 30 days after last dose of ReposMBZ or start of new treatment, whatever comes first, assessed up to 20 weeks after start of treatment phase.

• Changes in plasma Bilirubin over time

  Blood chemistry (plasma): Bilirubin (µmol/L)

  From date of first dose, up to 30 days after last dose of ReposMBZ or start of new treatment, whatever comes first, assessed up to 20 weeks after start of treatment phase.

• Changes in plasma ALAT (alanine aminotransferase), ASAT (aspartate aminotransferase), LDH (lactate dehydrogenase), ALP (alkaline phosphatase) over time

  Blood chemistry (plasma): ALAT, ASAT, LDH, ALP (µkat/L)

  From date of first dose, up to 30 days after last dose of ReposMBZ or start of new treatment, whatever comes first, assessed up to 20 weeks after start of treatment phase.

• Changes in Haemoglobin over time

  Haematology: Haemoglobin (g/L)

  From date of first dose, up to 30 days after last dose of ReposMBZ or start of new treatment, whatever comes first, assessed up to 20 weeks after start of treatment phase.

• Changes in red, white and platelet blood cell count over time

  Haematology: RBC (red blood cell count), White blood cells with differential count and platelets (absolute count/L)

  From date of first dose, up to 30 days after last dose of ReposMBZ or start of new treatment, whatever comes first, assessed up to 20 weeks after start of treatment phase.

• Changes in Activated Partial Thromboplastin Time (APTT) over time

  Coagulation (plasma): APTT (s)

  From date of first dose, up to 30 days after last dose of ReposMBZ or start of new treatment, whatever comes first, assessed up to 20 weeks after start of treatment phase.

• Changes in Prothrombin complex (PK/INR) over time

  Coagulation (plasma): Prothrombin complex (INR)

  From date of first dose, up to 30 days after last dose of ReposMBZ or start of new treatment, whatever comes first, assessed up to 20 weeks after start of treatment phase.

• Changes in blood pressure over time

  Systolic and diastolic blood pressure (mmHg) Weight (kg)

  From date of first dose, up to 30 days after last dose of ReposMBZ or start of new treatment, whatever comes first, assessed up to 20 weeks after start of treatment phase.

• Changes in heart rate over time

  Supine heart rate (beats per minute)

  From date of first dose, up to 30 days after last dose of ReposMBZ or start of new treatment, whatever comes first, assessed up to 20 weeks after start of treatment phase.

• Changes in body temperature over time.

  Body temperature (Celsius degrees)

  From date of first dose, up to 30 days after last dose of ReposMBZ or start of new treatment, whatever comes first, assessed up to 20 weeks after start of treatment phase.

• Tumour response: CT/MRI assessed according to RECIST 1.1

  Best overall radiological response Time to tumour progression (TTP) compared with TTP on the treatment just preceding this protocol.

  From date of first dose ReposMBZ until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 24 months (end of study).

Secondary Outcomes (9)

• The peak serum concentration (Cmax) of ReposMBZ after single dose administration.

  Pre-dose, 30 minutes, 60 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours.

• Area under the serum concentration versus time curve (AUC) for ReposMBZ

  Pre-dose, 30 minutes, 60 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours.

• The Cmax serum concentration of ReposMBZ after repeated dose administration.

  Pre-dose, 30 minutes, 60 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours (only up to the time point for Cmax after single dose), assessed up to 16 weeks after start of treatment phase.

• Target S-mebendazole concentration after repeated dose administration.

  From first dose in treatment phase and assessed up to 16 weeks after start of treatment phase.

• Time to reach the steady state S-mebendazole target concentration after repeated dose administration..

  From first dose in treatment phase and assessed up to 16 weeks after start of treatment phase.

Other Outcomes (3)

• Association between ReposMBZ efficacy and properties of the diagnostic tumour tissue (optional)

  Assessed up to 24 months (end of study).

• Comparison of diagnostic tissue and a fresh tumour biopsy after 4 weeks of treatment at the target S-mebendazole concentration (optional).

  Collected up to 20 weeks after start of treatment phase, assessed up to 24 months (end of study).

• Association between S-mebendazole and efficacy and safety

  From date of first dose until date of first documented progression or date of death, whichever comes fist, assessed up to 24 months (end of study).

Study Arms (1)

Single arm study

EXPERIMENTAL

ReposMBZ 100 mg capsule by mouth followed by 8h PK sampling to decide the initial daily dose. Treatment: Repos MBZ capsules by mouth twice daily for 16 weeks, daily dose 50mg-4g, based on the serum level of mebendazole.

Drug: ReposMBZ

Interventions

ReposMBZ DRUG

Capsules 50mg, 100mg, 200mg

Also known as: Mebendazole

Single arm study

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age.
• Histologically confirmed diagnosis of squamous cell cancer or adenocarcinoma, including primary cancer of the liver, of the gastrointestinal tract or cancer of unknown origin.
• Measurable disease according to RECIST 1.1.
• Defined time to tumour progression on the standard/experimental treatment preceding the trial treatment.
• Locally advanced or metastatic disease not amenable to standard treatment, i.e. progress on standard therapy or observed/expected intolerance to standard therapy.
• \- (removed via Amendment 1)
• Pharmacological treatment attempt considered reasonable.
• Females of childbearing potential should use adequate contraception throughout the study;
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal)
• Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable)
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)
• Bilateral tubal occlusion
• Vasectomized partner
• Sexual abstinence

You may not qualify if:

• Anti-tumour therapy within 3 weeks prior to study drug administration day
• Ongoing infection or other major recent or ongoing disease that, according to the investigator, poses an unacceptable risk to the patient.
• WHO performance status ≥ 2.
• Child-Pugh B or C liver function status if hepatocellular carcinoma.
• Inadequate laboratory parameters reflecting major organ function i.e.:
• neutrophils ≤ 1,3 x 109/l
• platelets ≤ 100 x 109/l
• bilirubin \> 1.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALAT) \> 5 x ULN
• Glomerular filtration rate (GFR) \<50 ml/min (calculated from P-creatinine)
• Prothrombin complex/INR outside normal range
• Current active participation in any other interventional clinical study.
• Contraindications to the investigational product, e.g. known or suspected hypersensitivity or inability to oral drug administration.
• Pregnancy or lactation.
• Lack of suitability for participation in the study, e g expected difficulties to follow the protocol procedures, as judged by the Investigator.

Sponsors & Collaborators

• Repos Pharma: lead
• Uppsala University: collaborator
• Uppsala University Hospital: collaborator

Study Sites (1)

Dept of oncology, University Hospital

Uppsala, 75185, Sweden

Location

MeSH Terms

Conditions

Gastrointestinal Neoplasms; Neoplasms, Unknown Primary

Interventions

Mebendazole

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Neoplasm Metastasis; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2018
• First Posted: August 14, 2018
• Study Start: May 25, 2018
• Primary Completion: January 16, 2019
• Study Completion: January 16, 2019
• Last Updated: January 22, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)