This trial is active, not recruiting.

Condition prostate cancer
Treatment metformin hydrochloride
Phase phase 2
Sponsor Swiss Group for Clinical Cancer Research
Start date December 2010
End date September 2017
Trial size 44 participants
Trial identifier NCT01243385, CDR0000688789, SAKK 08/09, SWS-SAKK-08/09


RATIONALE: Metformin hydrochloride may make some enzymes active. These enzymes may block other enzymes needed for cell growth and stop the growth of tumor cells.

PURPOSE: This phase II trial is studying the safety of giving metformin hydrochloride as first-line therapy in treating patients with locally advanced or metastatic prostate cancer.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Intervention model single group assignment
Masking open label
Primary purpose treatment
metformin hydrochloride Metformin-Mepha
Metformin Lifelong follow-up at a target dose of 2 x 1000 mg daily Until progression, unacceptable toxicity or refusal

Primary Outcomes

Progression-free survival (PFS)
time frame: at 12 weeks

Secondary Outcomes

time frame: at 24 weeks
Clinical benefit rate
time frame: at 12 weeks and 24 weeks
Time to treatment failure
time frame:
Adverse events
time frame:
Prostate-specific antigen (PSA) response
time frame: (50% and 30%, best and at 12 weeks)
Changes in PSA doubling time
time frame:
Tumor response of measurable disease according to RECIST v 1.1 criteria
time frame:
Tumor assessment of bone lesions
time frame:
Overall survival
time frame:

Eligibility Criteria

Male participants at least 18 years old.

DISEASE CHARACTERISTICS: - Histologically confirmed adenocarcinoma of the prostate - Locally advanced or metastatic disease with no curative therapy possible - PSA progression defined as the following: - Increase in PSA of ≥ 25% (and an absolute increase of ≥ 2 ng/mL) over nadir value on hormonal therapy measured on 3 successive occasions at least 1 week apart - If the third measurement is not higher than the second, a fourth measurement will be taken and only if the fourth measurement is higher than the second, the patient may be enrolled - PSA doubling time ≥ 55 days (if used to define progression, must not be older than 6 months) - PSA < 114 ng/mL - Testosterone level ≤ 1.7 nmol/L (≤ 50 ng/dL) after at least 1 hormonal treatment (orchiectomy or luteinizing hormone-releasing hormone [LHRH] agonist) - Patients who have not undergone surgical castration must continue LHRH agonist therapy during study treatment - Oligosymptomatic or asymptomatic in relation to disease - No known or suspected CNS metastases PATIENT CHARACTERISTICS: - WHO performance status 0-1 - Hemoglobin ≥ 90 g/L - Neutrophil count ≥ 1.5 x 10^9/L - Platelet count ≥ 100 x 10^9/L - AST ≤ 2.5 times upper limit of normal (ULN) - Bilirubin ≤ 1.5 times ULN - Creatinine clearance ≥ 60 mL/min - Compliant and geographically proximal for proper staging and follow-up - No previous malignancy within the past 2 years except for localized nonmelanoma skin cancer or Ta or Tis bladder cancer - No history of diabetic ketoacidosis, diabetic coma, or pre-coma - No known history of HIV, hepatitis B, or hepatitis C positivity - No known hypersensitivity to the trial drug or any of its components - No serious underlying medical condition that, in the judgment of the investigator, would impair the ability of the patient to participate in the trial (e.g., uncontrolled or acute severe infection, uncontrolled diabetes, advanced chronic obstructive pulmonary disease [COPD], or heart failure) - No psychiatric disorder precluding understanding of information on trial related topics, giving informed consent, or interfering with compliance for oral drug intake - No known alcohol abuse PRIOR CONCURRENT THERAPY: - See Disease Characteristics - At least 6 weeks since prior antiandrogen therapy and without withdrawal response - At least 30 days since prior treatment in another clinical trial - At least 4 weeks since prior major surgery - At least 4 weeks since prior products known to affect PSA levels - At least 2 weeks since prior local radiation - No prior chemotherapy, radioisotopes, small molecules, or immunotherapy for prostate cancer - No prior metformin hydrochloride - No concurrent pharmacotherapy for diabetes mellitus - No concurrent finasteride, dutasteride, ketoconazole, or abiraterone acetate - No concurrent corticosteroids with an equivalent dose of > 7.5 mg of prednisolone - No concurrent radiotherapy - No bisphosphonates started after registration - No concurrent drugs contraindicated for use with the trial drug according to the Swissmedic approved product information - No other concurrent anticancer drugs - No other concurrent experimental or investigational drugs

Additional Information

Official title Metformin in Castration Resistant Prostate Cancer. A Multicenter Phase II Trial.
Description OBJECTIVES: - To determine the activity and safety of metformin hydrochloride as first-line therapy in patients with locally advanced or metastatic castration-resistant prostate cancer. OUTLINE: This is a multicenter study. Patients receive oral metformin hydrochloride twice daily on days 1-28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. Previously collected and post-treatment tumor tissue may be analyzed for PTEN status and PI3kinase-dependent pathway activation via immunohistochemistry. Blood samples may also be collected periodically and analyzed for biomarkers, pharmacogenetics, pharmacodynamics, pharmacokinetics. After completion of study therapy, patients are followed up every 3 months.
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by Swiss Group for Clinical Cancer Research.