Metformin Hydrochloride as First-Line Therapy in Treating Patients With Locally Advanced or Metastatic Prostate Cancer

Phase 2

Completed

• Conditions: Prostate Cancer
• Interventions: Drug: Metformin

• Registration Number: NCT01243385
• Lead Sponsor: Swiss Group for Clinical Cancer Research

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2010-11-17
• Study First Submitted QC: 2010-11-17
• Study First Posted: 2010-11-18
• Study Start: 2010-12-23
• Primary Completion: 2012-04-17
• Status Verified: 2019-08
• Study Completion: 2019-08-09
• Last Update Submitted: 2019-08-12
• Last Update Posted: 2019-08-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 44

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Metformin	Metformin	Metformin at a target dose of 2 x 1000 mg daily Until progression, unacceptable toxicity or refusal

Primary Outcome Measures

Name	Time	Method
Progression-free survival (PFS) at 12 weeks	at 12 weeks	PFS is defined as the absence of disease progression or death at 12 weeks after start of treatment.

Secondary Outcome Measures

Name	Time	Method
Adverse events	from start of treatment until progression or death of any cause	All AEs will be assessed according to NCI CTCAE v4.0
PFS at 24 weeks	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	at 12 weeks and 24 weeks	Clinical benefit is defined as SD by imaging and symptoms - with or without PSA progression
Prostate-specific antigen (PSA) response	(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	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	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	at 12 weeks	Bone metastases can be assessed by radionuclide bone scan.
Overall survival	from registration until death	OS will be calculated from registration until death

Trial Locations

Locations (9)

Universitaetsspital-Basel; 🇨🇭 Basel, Switzerland

Kantonsspital Luzern; 🇨🇭 Luzerne, Switzerland

Kantonsspital - St. Gallen; 🇨🇭 St. Gallen, Switzerland

Kantonsspital Aarau; 🇨🇭 Aarau, Switzerland

Inselspital Bern; 🇨🇭 Bern, Switzerland

Kantonsspital Graubuenden; 🇨🇭 Chur, Switzerland

Kantonsspital Winterthur; 🇨🇭 Winterthur, Switzerland

Onkozentrum; 🇨🇭 Zurich, Switzerland

UniversitaetsSpital Zuerich; 🇨🇭 Zurich, Switzerland