Impact of the Addition of Metformin to Abiraterone in Metastatic Prostate Cancer Patients (MetAb-Pro)

Impact of the Addition of Metformin to Abiraterone in Pre-docetaxel Metastatic Castration-resistant Prostate Cancer Patients Progressing on Abiraterone Treatment (MetAb-Pro): a Phase II Pilot Study

The purpose of this study is to assess the impact of the addition of metformin to abiraterone on survival in patients with metastatic prostate cancer

Study Overview

• Status: Completed
• Conditions: Metastatic Prostate Cancer
• Intervention / Treatment: Drug: Metformin

Detailed Description

The purpose of this study is to assess the impact of the addition of metformin to abiraterone on survival in patients with metastatic chemotherapy-naive prostate cancer

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • Graubünden
    • Chur, Graubünden, Switzerland, 7000
      • Kantonsspital Graubunden

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Metastatic adenocarcinoma of the prostate.
• Patient must give written informed consent before registration.
• Age ≥18 years.
• WHO performance status 0-2.
• Tumor progression (as defined below) after at least 1 hormonal treatment (orchiectomy, LHRH agonist) with documented total testosterone levels ≤ 1.7 nmol/L (≤ 50 ng/dL). Ongoing concurrent use of LHRH agonist is required if the patient has not been surgically castrated.

• PSA progression during treatment with abiraterone (at least 12 weeks of treatment) defined as follows:

  • In case PSA levels had not decreased under treatment: ≥ 25% increase over baseline (at registration) AND an increase in the absolute PSA value of ≥ 5 ng/mL.
  • In case of PSA response < 50% under treatment: ≥ 25% increase over the nadir AND an increase in the absolute PSA value of ≥ 5 ng/mL.
  • In case of PSA response ≥ 50% under treatment: ≥ 50% increase over the nadir AND an increase in the absolute PSA value of ≥ 5 ng/mL Note: PSA progression has to be confirmed at least 1 week later. In case of confirmation the first date of PSA rise is relevant for the calculation.
• Serum potassium ≥ 3.5mmol/L.
• Adequate hematological values: neutrophils ≥1.5x109/L, platelets ≥100x109/L.
• Adequate hepatic function: bilirubin ≤1.5 x ULN, ALT ≤2.5 x ULN.
• Adequate renal function (calculated creatinine clearance ≥50 mL/min, according to the formula of Cockcroft-Gault).
• Able to swallow study drug as whole tablet.
• Patient compliance and geographic proximity allow proper staging and follow-up.

Exclusion Criteria:

• Previous malignancy within 2 years with the exception of localized non-melanoma skin cancer and Ta and Tis bladder cancer.
• Known CNS or spinal cord metastases.
• Active autoimmune disease requiring higher doses of corticosteroid than the equivalent of prednisone 10mg/d.
• Radiotherapy within the last 2 weeks before start of the trial treatment.
• Patients treated with anti-androgens such as flutamide or bicalutamide, if not discontinued at least 4 weeks prior to registration in case of response or in case of no response 2 weeks prior to inclusion for wash-out reasons.
• Prior treatment with metformin Prior treatment with metformin
• Diabetic ketoacidosis, diabetic coma and precoma
• Concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to trial entry, except treatment with bisphosphonates and LHRH agonists.
• Known hypersensitivity to trial drugs or hypersensitivity to any of their components.
• Concomitant drugs contraindicated for use with the trial drugs according to the Swissmedic-approved product information.
• Uncontrolled hypertension, history of cardiac failure NYHA class III or IV.
• Serious underlying medical condition (at the judgment of the investigator) which could impair the ability of the patient to participate in the trial (e.g. uncontrolled or acute severe infection, uncontrolled diabetes).
• Active or symptomatic viral hepatitis or chronic liver disease.
• History of pituitary or adrenal dysfunction.
• Gastrointestinal disorder affecting absorption.
• Psychiatric disorder precluding understanding of information on trial related topics, giving informed consent, or interfering with compliance for oral drug intake.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Metformin; Metformin 2x1000mg orally per day	Drug: Metformin; Adding Metformin to Abiraterone in case of PSA-Progression; Other Names: Abiraterone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
progression free survival	at 12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
overall survival	up to 2 years

Other Outcome Measures

Outcome Measure	Time Frame
progression free survival at 24 weeks	at 24 weeks
progression free survival	up to 24 weeks
psa response	at 12 weeks
number of adverse events according to the NCI CTCAE v4.0	up to 24 weeks

Collaborators and Investigators

• Sponsor: Kantonsspital Graubünden
• Collaborators: Janssen-Cilag Ltd.
• Investigators: Principal Investigator: michael mark, md, Kantonsspital Graubunden

Publications and helpful links

General Publications

• Mark M, Klingbiel D, Mey U, Winterhalder R, Rothermundt C, Gillessen S, von Moos R, Pollak M, Manetsch G, Strebel R, Cathomas R. Impact of Addition of Metformin to Abiraterone in Metastatic Castration-Resistant Prostate Cancer Patients With Disease Progressing While Receiving Abiraterone Treatment (MetAb-Pro): Phase 2 Pilot Study. Clin Genitourin Cancer. 2019 Apr;17(2):e323-e328. doi: 10.1016/j.clgc.2018.12.009. Epub 2019 Jan 2.

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (ACTUAL): December 1, 2017
• Study Completion (ACTUAL): June 1, 2018

Study Registration Dates

• First Submitted: August 28, 2012
• First Submitted That Met QC Criteria: August 29, 2012
• First Posted (ESTIMATE): September 3, 2012

Study Record Updates

• Last Update Posted (ACTUAL): March 5, 2019
• Last Update Submitted That Met QC Criteria: March 3, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: MetAb-Pro