Repurposing Metformin as Anticancer Drug: in Advanced Prostate Cancer (Mansmed)

April 29, 2017 updated by: Reham Algahndour, Mansoura University

Mansmed Trial : Repurposing Metformin as Anticancer Drug, RCT in Advanced Prostate Cancer

This study evaluate the addition of metformin to standard of care in locally advanced and metastatic prostate cancer, half the patient will receive metformin in combination with standard treatment, and the other half will receive the standard of care only

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Advanced-stage PCa is usually treated with androgen-deprivation therapy (ADT). Most patients with metastatic disease who were managed with ADT eventually progress to castration-resistant prostate cancer (CRPC) and die of the disease. CRPC can be treated with docetaxel, abiraterone plus prednisone, enzalutamide, and cabazitaxel, which provide limited survival benefits. Thus, there is still a need to improve the therapeutic options available for advanced-stage prostate cancer patients. Targeting therapy-resistant cancer stem cells (CSCs )in prostate cancer provides a unique opportunity for novel therapeutic interventions.

Metformin, a common well-tolerated oral biguanide prescribed for type II diabetes, could be used to sensitize prostate CSCs to current conventional anticancer therapies and improve the efficacy of treatment. Some studies reported that Metformin could enhance the effectiveness of ADT. Metformin augmented the antiproliferative and apoptotic effects of ADT in prostate cancer. The combination of these two drugs significantly reduces prostate cancer cell growth compared to monotherapy with either drug. Also, metformin might reduce the development of CRPC.

Many studies showed that obesity and DM were linked to aggressive prostate cancer phenotype, including biochemical failure after radical prostatectomy and external beam radiotherapy with higher incidence of complications of ADT. Interestingly, metformin reduces the incidence of diabetes and the adverse metabolic effects of ADT, including hyperinsulinaemia and dyslipidaemia, and decreases myocardial infarction risk and prolongs survival in diabetic patients.

To the best of our knowledge, after extensive computer research, there is no published results from prospective randomized trials evaluating role of metformin among men with high risk locally advanced or metastatic prostate cancer patients who will start treatment with ADT.

Study Type

Interventional

Enrollment (Anticipated)

120

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Egypt
      • Mansourah, Egypt, 35516

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  1. High-risk newly diagnosed non-metastatic node-negative disease at least two of:

    • Stage T3/4, PSA≥40ng/ml or Gleason sum score 8-10
    • Intention to treat with radical radiotherapy (unless there is a contraindication)

  2. OR newly diagnosed metastatic or node-positive disease at least one of:

    • Stage T any N+ M0
    • Stage T any Nany M+

  3. OR previously treated with radical surgery and/or radiotherapy, now relapsing

    At least one of:

    (-PSA ≥4ng/ml and rising with doubling time less than 6 months,N+, M+)

  4. And for all patients

    • Age > 18 years
    • Histologically confirmed prostate adenocarcinoma
    • Intention to treat with long-term androgen deprivation therapy
    • Fit for all protocol treatment and follow-up, ECOG performance status 0-2
    • Diabetic and non-diabetic patients
    • Patients with adequate organ function(AST - ALAT ≤ 2.5x ULN,Bilirubin ≤ 1.5 x ULN)

Exclusion Criteria:

  1. Age < 18 years
  2. Excessive alcohol intake, acute or chronic
  3. Patients already treated with Metformin or an analoge
  4. Known hypersensitivity or allergy to Metformin or any of the excipients.
  5. Patients with a history of lactic acidosis
  6. Patient treated for a cancer other than prostate cancer, with the exception of basal cell carcinoma
  7. Acute or chronic metabolic acidosis.
  8. Patients suffering from severe dehydration.
  9. Patients with chronic heart failure.
  10. Patients with hepatic impairment.
  11. Patients with severe renal disease.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Investigational arm
Metformin will be added to standard of care
Drug: Metformin
Metformin will be added as a daily treatment to the standard treatment in both neoadjuvant and adjuvant settings of locally advanced cases and lifelong to metastatic cases. The starting daily dose of metformin is 850mg Once daily, to be increased to 850 mg if tolerated
Other Names:
  • Cidophage
No Intervention: Control arm
Patients will treated according to Standard of care only

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
duration in months from beginning of treatment till development of CRPC
Time Frame: 2 years
time till development of CRPC [Castrate resistant prostate cancer], is defined by disease progression despite androgen depletion therapy (ADT) and may present as either a continuous rise in serum prostate-specific antigen (PSA) levels, the progression of pre-existing disease, and/or the appearance of new metastases.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CRPC free survival
Time Frame: 4 years
Number of survivors without CRPC at 4 years
4 years
Overall patients' survival
Time Frame: 4 years
Number of overall survivors at 4 years regardless occurrence of CRPC or not
4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mansoura University

Investigators

  • Principal Investigator: Reham Alghandour, Mansoura University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2017

Primary Completion (Anticipated)

January 1, 2018

Study Completion (Anticipated)

January 1, 2020

Study Registration Dates

First Submitted

April 9, 2017

First Submitted That Met QC Criteria

April 29, 2017

First Posted (Actual)

May 2, 2017

Study Record Updates

Last Update Posted (Actual)

May 2, 2017

Last Update Submitted That Met QC Criteria

April 29, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Mansmed trial I

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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