LIpitor and biGuanide to Androgen Delay Trial

A Randomized, Double Blind, Trial of Metformin and Atorvastatin in Delaying Androgen Deprivation Therapy Among Men With Rising PSA Following Radical Prostatectomy or Radiotherapy: The LIGAND (LIpitor and biGuanide to Androgen Delay) Trial

This study is a randomized trial examining the administration of a combination of biguanide metformin and atorvastatin ("Lipitor") to men who are experiencing rising prostate-specific antigen (PSA) levels, despite having undergone radical therapy (surgery and/or radiation).

Inclusion Criteria:

• Willing and able to provide informed consent
• Histologically confirmed adenocarcinoma of the prostate
• History of radical therapy (i.e., radical prostatectomy, radiotherapy, brachytherapy or prostatectomy with salvage radiotherapy)
• Serum testosterone levels 8.0 nmol/L (230 ng/dL) or greater
• Not currently undergoing treatment for hyperlipidemia or diabetes mellitus
• LDL-cholesterol levels 5 mmol/L or lower
• HgA1c 6.5% or lower
• PSA levels between 2 and 5 ng/mL

Exclusion Criteria:

• Subjects that have been treated for prostate cancer with any of the following:

  i. Cytotoxic chemotherapy; ii. Hormonal therapy within past 3 years; iii. Oral glucocorticoids; iv. Gonadotropin-releasing hormone (GnRH) analogues (e.g., leuprolide, goserelin, degarelix)

• Past treatment with the 5-α reductase inhibitors finasteride and dutasteride within past 5 years

• Past treatment with drugs with antiandrogenic properties (e.g., flutamide, bicalutamide, ketoconazole, progestational agents) within 6 months prior to screening

• Use of metformin or statins within past 2 years

• Planned or concurrent use of metformin, sulfonylureas, thiazolidinediones or insulin for any reason

• Known hypersensitivity or intolerance to metformin or atorvastatin

• Any clinically significant laboratory abnormalities (e.g., severe renal or hepatic impairment) which in the judgment of the investigator would affect the patient's health or the outcome of the trial

• Any condition associated with increased risk of metformin-associated lactic acidosis (e.g., congestive heart failure defined as New York Heart Association (NYHA) class III or IV, history of any type of acidosis, habitual intake of 4 or more alcoholic beverages per day)

• Abnormal liver function test

• Abnormal organ and marrow function