PREMIUM: Prevention of Metabolic Syndrome and Increased Weight Using Metformin Concurrent to Androgen Deprivation Therapy and Radiotherapy for Locally Advanced Adenocarcinoma of the Prostate

Sponsor

AHS Cancer Control Alberta (Other)

Overall Status

Unknown status

CT.gov ID

NCT01996696

Collaborator

(none)

104

Enrollment

Locations

Arms

Duration (Months)

34.7

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In current clinical practice, an acceptable standard treatment for locally advanced prostate cancer is radiation therapy in combination with hormone therapy (called Treatment B or Group B in this study). However, despite our best treatments, there is a risk that the prostate cancer may eventually return. As well, the hormonal therapy that is given to treat the prostate cancer is known to cause some harmful effects, with some patients using the hormones gaining weight, developing diabetes, having increased cholesterol levels, having increased blood pressure, and/or heart problems.

This study is looking at whether Metformin, a drug that is commonly used to treat diabetes, can prevent patients from developing some of the harmful effects of the hormonal therapy. In treating diabetes, Metformin is known to decrease patients' sugar levels and also prevents patients from gaining weight, decreases their cholesterol levels, decreases the number of heart problems and allows patients to live longer. As a result, the researchers in this study are hopeful that Metformin will also be beneficial for men with prostate cancer on hormonal therapy by preventing them from developing these problems.

Condition or Disease	Intervention/Treatment	Phase
Prostatic Neoplasm	Drug: Metformin Drug: Placebo	Phase 2

Detailed Description

This study will examine the role of Metformin as a means to prevent increases in weight as well as the prevalence and severity of metabolic syndrome, with their associated morbidity, amongst men with locally advanced, biopsy confirmed adenocarcinoma of the prostate (PCa) that are planned to receive curative intent therapy with androgen deprivation therapy (ADT) and external beam radiotherapy (EBRT) to the prostate.

Males of any age with biopsy confirmed high tier intermediate risk PCa (Gleason score 7 and PSA 10-20) or high risk PCa (any T3; and/or Gleason Score ≥ 8.0; and/or PSA ≥ 20 ng/mL) ECOG 0 to 1, non-diabetic with no evidence of metastatic PCa will be randomized to either:

Group A: Metformin 500mg PO TID x 30-36 months total, with neoadjuvant and adjuvant ADT x18-36 months and EBRT of 46 Gy/23# to pelvic lymph nodes (optional); plus prostate boost to 78 Gy/39# or brachytherapy boost (110-115 Gy) or hypofractionated equivalent

Group B: Identical placebo TID x 20-36 months total, with neoadjuvant and adjuvant ADT x18-36 months and EBRT of 46 Gy/23# to pelvic lymph nodes (optional); plus prostate boost to 78 Gy/39# or brachytherapy boost (110-115 Gy) or hypofractionated equivalent

A planned sample size of 104 patients will provide 97% power for a 2-tailed α of 0.05 to detect 4 kg difference in weight at 12 months of follow-up.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

104 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Prevention of Metabolic Syndrome and Increased Weight Using Metformin Concurrent to Androgen Deprivation Therapy and Radiotherapy for Locally Advanced Adenocarcinoma of the Prostate

Study Start Date :

Sep 1, 2014

Anticipated Primary Completion Date :

Sep 1, 2021

Anticipated Study Completion Date :

Sep 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Metformin Metformin 500 mg PO TID x 30-36 months	Drug: Metformin Metformin 500 mg PO TID x 30-36 months Other Names: Fortamet Glucophage Glucophage XR Glumetza Riomet
Placebo Comparator: Placebo Identical placebo TID x 30-36 months	Drug: Placebo Identical placebo TID x 30-36 months

Arm

Intervention/Treatment

Experimental: Metformin

Metformin 500 mg PO TID x 30-36 months

Drug: Metformin

Metformin 500 mg PO TID x 30-36 months

Other Names:

Fortamet

Glucophage

Glucophage XR

Glumetza

Riomet

Placebo Comparator: Placebo

Identical placebo TID x 30-36 months

Drug: Placebo

Identical placebo TID x 30-36 months

Outcome Measures

Primary Outcome Measures

Mean body weight at 12 months of follow-up [12 months of follow-up]

Secondary Outcome Measures

Prevalence and incidence of Metabolic Syndrome [At 6, 12, 24 and 36 months follow-up]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

Males ≥ 18 years of age
Pathologically confirmed, adenocarcinoma of the prostate with either high-tier intermediate or high risk prostate cancer:

High-tier intermediate risk prostate cancer: i. Gleason score = 7 and PSA 10 - 20 ng/mL b. High risk prostate cancer: i. any T3; or ii. Gleason Score ≥ 8.0; or iii. PSA ≥ 20 ng/mL.

Normoglycemic or Impaired Fasting Glucose45 defined as:
Fasting Plasma Glucose of ≤ 6.9; or
HbA1c of <6.5%
Deemed fit to undergo curative intent external beam radiation therapy with concurrent androgen deprivation therapy by their attending radiation oncologist.
Accessible for follow-up clinical and laboratory assessments.

Exclusion Criteria:

Patients with evidence (either by imaging or pathology) of distant metastatic spread of their disease.

Patients with pelvic lymph nodes (i.e. N1 disease) are NOT considered to have distant metastases and can be included in the trial, if meeting the other study criteria.

Patients that meet ≥1 of the Canadian Diabetes Association criteria45 for the diagnosis of diabetes:
Fasting Plasma Glucose of ≥ 7.0 mmol/L; or
HbA1C ≥ 6.5%; or
Plasma Glucose level of ≥ 11.1 mmol/L 2 hours following a 75g oral glucose load, if known, within past 28 days; or
Random Plasma Glucose level of ≥ 11.1 mmol/L, if known, within past 28 days
Patient who currently take metformin or those who have taken metformin within the past 12 months.
History of lactic acidosis or conditions that predispose to lactic acidosis including32:

Impaired Renal Function (eGFR < 30); or b. Liver disease, including alcoholic liver disease, as demonstrated by any of the following parameters: i. AST >1.8 x the upper limit of normal ii. ALT > 1.8 x the upper limit of normal iii. Alkaline Phosphatase > 2x the upper limit of normal iv. Serum total bilirubin ≥ upper limit of normal c. Alcohol abuse (habitual intake of ≥3 alcoholic beverages per day) sufficient to cause hepatic toxicity d. Severe infection

Patients with prior bilateral orchiectomy.
Patients with prior prostatectomy
Patients who are unable to provide informed consent
Prior history of malignancy (with exception of adequately treated non-melanomatous skin cancer or other solid tumors treated curatively with no evidence of disease for ≥ 5 years).
Patients on hormonal therapy for more than 3 months prior to registration in the trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
2	Prairie Mountain Health - Western Manitoba Cancer Centre	Brandon	Manitoba	Canada	R7A2B3
3	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9