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Cancer of the Gastrointestinal TractPhase 1/2RepoMebNCT03628079

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

A Phase 1/2 study testing ReposMBZ in people with Cancer of the Gastrointestinal Tract and Cancer of Unknown Origin, run by Repos Pharma at 1 site in Sweden.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
ReposMBZ
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
1 siteSweden
Study dates
25 May 2018to 16 Jan 2019
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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
  • Signed informed consent.

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

1 site in 1 country.

Sweden1 site
  • Dept of oncology, University Hospital

    Uppsala, 75185

Other trials in Sweden

About this study

Official title: A Phase 2a TDM-guided Clinical Study on the Safety and Efficacy of Mebendazole in Patients With Advanced Gastrointestinal 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.

Read the detailed description

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.

Being tested
ReposMBZ
Medical subject headings
Gastrointestinal Neoplasms, Neoplasms, Unknown Primary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ReposMBZDrug

    Also called Mebendazole

    Capsules 50mg, 100mg, 200mg

Study groups in NCT03628079
Study groupRoleWhat they receive
Single arm studyExperimentalReposMBZ 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.
Receives: Drug: ReposMBZ

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    AEs graded according to CTCAE 4.03.

    Measured: 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.

  2. Changes in plasma Albumin over time

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

    Measured: 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.

  3. Changes in C-reactive protein (CRP) over time

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

    Measured: 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.

  4. Changes in plasma Sodium, Potassium, Calcium and Glucose over time

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

    Measured: 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.

  5. Changes in plasma Bilirubin over time

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

    Measured: 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.

  6. 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)

    Measured: 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.

  7. Changes in Haemoglobin over time

    Haematology: Haemoglobin (g/L)

    Measured: 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.

  8. 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)

    Measured: 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.

  9. Changes in Activated Partial Thromboplastin Time (APTT) over time

    Coagulation (plasma): APTT (s)

    Measured: 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.

  10. Changes in Prothrombin complex (PK/INR) over time

    Coagulation (plasma): Prothrombin complex (INR)

    Measured: 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.

  11. Changes in blood pressure over time

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

    Measured: 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.

  12. Changes in heart rate over time

    Supine heart rate (beats per minute)

    Measured: 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.

  13. Changes in body temperature over time.

    Body temperature (Celsius degrees)

    Measured: 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.

  14. 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.

    Measured: 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)
  1. The peak serum concentration (Cmax) of ReposMBZ after single dose administration.

    Cmax will be used to decide the starting dose in the treatment phase.

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

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

    Analysis of serum concentration after single dose administration of ReposMBZ.

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

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

    Cmax will be used to adjust the dose until target S-mebendazole level is reached and to show the individual variation of S-mebendazole concentration over time

    Measured: 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.

  4. Target S-mebendazole concentration after repeated dose administration.

    Number of patients that reach the steady state S-mebendazole target concentration.

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

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

    Time from first dose in treatment phase until target S-mebendazole concentration is reached

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

  6. Systemic immune activation.

    Change of cytokine levels in blood, evaluated by cytokine array.

    Measured: From baseline up to 20 weeks after start of treatment phase, assessed up to 24 months (end of study).

  7. Immune cell activation.

    Up-regulation of activation markers compared to baseline, evaluated by flow cytometry.

    Measured: From baseline and up to 20 weeks after start of treatment phase, assessed up to 24 months (end of study).

  8. Overall survival.

    Months of survival from first dose until death of any cause.

    Measured: From date of first dose ReposMBZ to date of death, assessed up to 24 months (end of study).

  9. Change in tumour load and TTP according to irRECIST

    Best over all radiological response according to irRECIST 1.1.

    Measured: 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).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Aug 2018
  2. Study start25 May 2018
  3. Primary completion16 Jan 2019
  4. Study completion16 Jan 2019

Why it stopped: Lack of effect

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03628079
Sponsor's protocol ID
RP-2017-001
Acronym
RepoMeb
Status last verified
Jan 2020
First submitted
17 Jun 2018
Last updated
22 Jan 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ReposMBZ in people with Cancer of the Gastrointestinal Tract and Cancer of Unknown Origin, run by Repos Pharma at 1 site in Sweden.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 22 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Lack of effect). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (AEs) probably or possibly related to ReposMBZ (time frame: 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.). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2020.

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