Phase II Study of Metformin in a Pre-prostatectomy Prostate Cancer Cohort
Description
Brief Summary
This randomized phase II trial studies how well metformin hydrochloride works compared to
placebo in treating patients with prostate cancer undergoing surgery. Metformin hydrochloride
may make some enzymes active. These enzymes may block other enzymes needed for cell growth
and stop the growth of tumor cells.
Detailed Description
I. To determine the effect of 4-12 weeks of metformin (metformin hydrochloride) intervention
on cell proliferation in the prostatectomy tissue.
SECONDARY OBJECTIVES:
I. To determine the effect of metformin intervention on prostate tissue bioavailability of
metformin.
II. To determine the effect of metformin intervention on apoptosis and angiogenesis in the
prostatectomy tissue.
III. To determine the effect of metformin intervention on potential molecular targets of
metformin including activated protein kinase (AMPK) activation, mammalian target of rapamycin
(mTOR) regulation, and cell cycle regulation in the prostatectomy tissue.
IV. To determine the effect of metformin intervention on changes in systemic hormones and
growth factors that have been shown to be modulated by metformin in other patient populations
including fasting glucose, fasting insulin, insulin-like growth factor axis, testosterone,
and sex hormone binding globulin (SHBG).
V. To determine the effect of metformin intervention on changes in prostate-specific antigen
(PSA) levels.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive extended-release metformin hydrochloride orally (PO) once daily (QD)
for 4-12 weeks.
ARM II: Patients receive placebo PO QD for 4-12 weeks.
Patients in both arms undergo surgery one day after completion of treatment.
After completion of study treatment, patients are followed up within 30 days of surgery.
Phase
Phase 2 - takes the treatment one step further, assessing the activity of a particular therapy in a disease, often building upon leads from the Phase I trial. While patients are generally required to be previously untreated, participation in a Phase II trial doesn't usually preclude the patient from getting the standard treatment after they've received the investigational agent. At best they are allowed to get a new drug they wouldn't be able to get otherwise that may turn out to be better for their disease.Inclusion and Exclusion Criteria
- Men will be eligible to this study if they are diagnosed with a histologically confirmed organ-confined adenocarcinoma of the prostate (PCa) treatable by prostatectomy and have a current PSA less than 50 ng/ml
- Have not received chemotherapy and/or radiation for any malignancy (excluding non-melanoma skin cancer and cancers confined to organs with removal as only treatment) in the past 5 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Karnofsky >= 70%)
- Leukocytes >= 3,000/uL
- Absolute neutrophil count >= 1,500/uL
- Platelets >= 100,000/uL
- Total bilirubin =< 1.5 times institutional upper limits of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 times institutional ULN
- Creatinine within normal institutional limits
- Willing to use adequate contraception (barrier method, abstinence, subject has had a vasectomy or partner is using effective birth control or is postmenopausal) for the duration of study participation
- Ability to understand and the willingness to sign a written informed consent document
- Type I or type II diabetic patients on treatment with any drug for diabetes or participants with fasting glucose >= 126 mg/dL
- History of impaired liver or kidney function
- Participants with a current history of high alcohol consumption (> 3 standard drinks/day) or binge drinking (5 or more drinks) in one session of 1-3 hours
- History of lactic acidosis or at increased risk for lactic acidosis such as patients with unstable or acute congestive heart failure who are at risk of hypoperfusion with hypoxemia
- Participants may not be receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical composition to metformin
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- History of acute or chronic metabolic acidosis
- Concurrent use of cationic drugs (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, or vancomycin)
- Concurrent use of non-study metformin or other biguanides
Sites
-
Arizona
- University of Arizona Health Sciences Center, Tucson, Arizona, 85724
Powered by
SC CTSI