Metformin Hydrochloride as First-Line Therapy in Treating Patients With Locally Advanced or Metastatic Prostate Cancer
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.
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Metformin in Castration Resistant Prostate Cancer. A Multicenter Phase II Trial.|
- Progression-free survival (PFS) at 12 weeks [ Time Frame: at 12 weeks ]PFS is defined as the absence of disease progression or death at 12 weeks after start of treatment.
- PFS at 24 weeks [ Time Frame: at 24 weeks ]PFS is defined as the absence of any disease progression or death at 24 weeks after start of treatment
- Clinical benefit rate [ Time Frame: at 12 weeks and 24 weeks ]Clinical benefit is defined as SD by imaging and symptoms - with or without PSA progression
- Adverse events [ Time Frame: from start of treatment until progression or death of any cause ]All AEs will be assessed according to NCI CTCAE v4.0
- Prostate-specific antigen (PSA) response [ Time Frame: (50% and 30%, best and at 12 weeks) ]
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.
- Changes in PSA doubling time [ Time Frame: after 12 weeks, after 24 weeks and at best PSA response ]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.
- Tumor response of measurable disease according to RECIST v 1.1 criteria [ Time Frame: after 12 weeks of treatment ]For patients with measurable disease at baseline RECIST v1.1 will be used to define CR, PR, SD and PD.
- Tumor assessment of bone lesions [ Time Frame: at 12 weeks ]Bone metastases can be assessed by radionuclide bone scan.
- Overall survival [ Time Frame: from registration until death ]OS will be calculated from registration until death
|Study Start Date:||December 2010|
|Estimated Study Completion Date:||September 2017|
|Estimated Primary Completion Date:||September 2017 (Final data collection date for primary outcome measure)|
Metformin at a target dose of 2 x 1000 mg daily Until progression, unacceptable toxicity or refusal
Metformin Lifelong follow-up at a target dose of 2 x 1000 mg daily Until progression, unacceptable toxicity or refusal
Other Name: Metformin-Mepha
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01243385
|Aarau, Switzerland, CH-5001|
|Basel, Switzerland, CH-4031|
|Bern, Switzerland, CH-3010|
|Chur, Switzerland, CH-7000|
|Luzerne, Switzerland, CH-6000|
|Kantonsspital - St. Gallen|
|St. Gallen, Switzerland, CH-9007|
|Winterthur, Switzerland, CH-8401|
|Zurich, Switzerland, 8038|
|Zurich, Switzerland, CH-8091|
|Study Chair:||Christian Rothermundt, MD||Cantonal Hospital of St. Gallen|
|Study Chair:||Richard Cathomas, MD||Kantonsspital Graubuenden|
|Study Chair:||Silke Gillessen, MD||Cantonal Hospital of St. Gallen|