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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
44
Metformin Lifelong follow-up at a target dose of 2 x 1000 mg daily Until progression, unacceptable toxicity or refusal
Kantonsspital Aarau
Aarau, Switzerland
Universitaetsspital-Basel
Basel, Switzerland
Inselspital Bern
Bern, Switzerland
Kantonsspital Graubuenden
Chur, Switzerland
Progression-free survival (PFS) at 12 weeks
PFS is defined as the absence of disease progression or death at 12 weeks after start of treatment.
Time frame: at 12 weeks
PFS at 24 weeks
PFS is defined as the absence of any disease progression or death at 24 weeks after start of treatment
Time frame: at 24 weeks
Clinical benefit rate
Clinical benefit is defined as SD by imaging and symptoms - with or without PSA progression
Time frame: at 12 weeks and 24 weeks
Adverse events
All AEs will be assessed according to NCI CTCAE v4.0
Time frame: from start of treatment until progression or death of any cause
Prostate-specific antigen (PSA) response
50 % PSA response is defined as a decrease in PSA level of at least 50 % (compared to baseline PSA). 30 % PSA response is defined as a decrease in PSA level of at least 30 % (compared to baseline PSA). Best response is defined as the percentage of change in PSA from baseline to the maximum decline in PSA at any point under treatment at 12 weeks or later. If there is a steady increase after baseline, the best response is defined as the percentage of change in PSA from baseline to the minimum increase in PSA at any point under treatment at 12 weeks or later.
Time frame: (50% and 30%, best and at 12 weeks)
Changes in PSA doubling time
PSA-DT is calculated from the natural log of 2 divided by the slope of the relationship between the log of PSA and the time of PSA measurement for each patient.
Time frame: after 12 weeks, after 24 weeks and at best PSA response
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Kantonsspital Luzern
Luzerne, Switzerland
Kantonsspital - St. Gallen
Sankt Gallen, Switzerland
Kantonsspital Winterthur
Winterthur, Switzerland
Onkozentrum
Zurich, Switzerland
UniversitaetsSpital Zuerich
Zurich, Switzerland
Tumor response of measurable disease according to RECIST v 1.1 criteria
For patients with measurable disease at baseline RECIST v1.1 will be used to define CR, PR, SD and PD.
Time frame: after 12 weeks of treatment
Tumor assessment of bone lesions
Bone metastases can be assessed by radionuclide bone scan.
Time frame: at 12 weeks
Overall survival
OS will be calculated from registration until death
Time frame: from registration until death