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

NCT ID: NCT01243385

Last Updated: 2019-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-23
• Study Completion Date: 2019-08-09

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Metformin

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

Group Type: OTHER

Metformin

Intervention Type: DRUG

Metformin Lifelong follow-up at a target dose of 2 x 1000 mg daily Until progression, unacceptable toxicity or refusal

Interventions

Metformin

Metformin Lifelong follow-up at a target dose of 2 x 1000 mg daily Until progression, unacceptable toxicity or refusal

Intervention Type: DRUG

Other Intervention Names

Metformin-Mepha

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christian Rothermundt, MD

Role: STUDY_CHAIR

Cantonal Hospital of St. Gallen

Richard Cathomas, MD

Role: STUDY_CHAIR

Kantonsspital Graubuenden

Silke Gillessen, MD

Role: STUDY_CHAIR

Cantonal Hospital of St. Gallen

Locations

Kantonsspital Aarau

Aarau, , Switzerland

Universitaetsspital-Basel

Basel, , Switzerland

Inselspital Bern

Bern, , Switzerland

Kantonsspital Graubuenden

Chur, , Switzerland

Kantonsspital Luzern

Luzerne, , Switzerland

Kantonsspital - St. Gallen

Sankt Gallen, , Switzerland

Kantonsspital Winterthur

Winterthur, , Switzerland

Onkozentrum

Zurich, , Switzerland

UniversitaetsSpital Zuerich

Zurich, , Switzerland

Countries

Switzerland

References

Rothermundt C, Hayoz S, Templeton AJ, Winterhalder R, Strebel RT, Bartschi D, Pollak M, Lui L, Endt K, Schiess R, Ruschoff JH, Cathomas R, Gillessen S. Metformin in chemotherapy-naive castration-resistant prostate cancer: a multicenter phase 2 trial (SAKK 08/09). Eur Urol. 2014 Sep;66(3):468-74. doi: 10.1016/j.eururo.2013.12.057. Epub 2014 Jan 4.

Reference Type: DERIVED

PMID: 24412228 (View on PubMed)

Other Identifiers

SWS-SAKK-08/09

Identifier Type: -

Identifier Source: secondary_id

CDR0000688789

Identifier Type: OTHER

Identifier Source: secondary_id

SAKK 08/09

Identifier Type: -

Identifier Source: org_study_id