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

Swiss Group for Clinical Cancer Research

Status and phase

Completed

Phase 2

Conditions

Prostate Cancer

Treatments

Drug: Metformin

Study type

Interventional

Funder types

Other

Identifiers

NCT01243385

SWS-SAKK-08/09

CDR0000688789 (Other Identifier)

SAKK 08/09

Details and patient eligibility

About

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.

Full 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.

Enrollment

44 patients

Sex

Male

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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