LIpitor and biGuanide to Androgen Delay Trial (LIGAND)

University Health Network, Toronto

Status and phase: Withdrawn; Phase 2

Conditions: Prostate Cancer

Treatments: Drug: Placebo (corresponding to metformin); Drug: Metformin; Drug: Atorvastatin; Drug: Placebo (corresponding to atorvastatin)

Study type: Interventional

Funder types: Other

Identifiers

NCT02497638

15-053

Details and patient eligibility

About

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).

Sex: Male

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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0 participants in 2 patient groups, including a placebo group

Metformin and Atorvastatin

Experimental group

Description:

Atorvastatin 20 mg once daily until progression with one month run-in of 850 mg metformin once daily, followed by 850 mg twice daily of metformin until progression.

Treatment:

Drug: Atorvastatin

Drug: Metformin

Placebo

Placebo Comparator group

Description:

One placebo tablet (corresponding to atorvastatin) once daily until progression, with one month of one placebo tablet (corresponding to metformin) once daily, followed by one placebo tablet twice daily until progression.

Treatment:

Drug: Placebo (corresponding to metformin)

Drug: Placebo (corresponding to atorvastatin)