A Study With or Without Metformin to Determine if Metformin Can Prevent Weight Gain and Other Problems (i.e. Diabetes, Increased Cholesterol, Etc.) That Can Arise From the Use of Hormonal Therapy in Combination With Radiation Therapy When Treating Aggressive Localized Prostate Cancer. (PREMIUM)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified December 2013 by AHS Cancer Control Alberta
Sponsor:
Information provided by (Responsible Party):
AHS Cancer Control Alberta
ClinicalTrials.gov Identifier:
NCT01996696
First received: November 22, 2013
Last updated: December 4, 2013
Last verified: December 2013
  Purpose

In current clinical practice, an acceptable standard treatment for high risk 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 Intervention Phase
Prostatic Neoplasm
Drug: Metformin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Prevention of Metabolic Syndrome and Increased Weight Using Metformin

Resource links provided by NLM:


Further study details as provided by AHS Cancer Control Alberta:

Primary Outcome Measures:
  • Mean body weight at 12 months of follow-up [ Time Frame: 12 months of follow-up ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Prevalence and incidence of Metabolic Syndrome [ Time Frame: At 6, 12, 24 and 36 months follow-up ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 104
Study Start Date: January 2014
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Metformin
Metformin 500 mg PO TID for 3 years
Drug: Metformin
Other Names:
  • Fortamet
  • Glucophage
  • Glucophage XR
  • Glumetza
  • Riomet
Placebo Comparator: Placebo
Identical placebo TID for 3 years
Drug: Placebo
Identical placebo TID for 3 years

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 high risk, 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 risk PCa (any T3; and/or Gleason Score ≥ 8.0; and/or PSA ≥ 20 ng/mL), ECOG 0-1, non-diabetic with no evidence of metastatic PCa will with randomized to either:

Group A: Metformin 500mg PO TID for 3 years total, with Neoadjuvant and adjuvant ADT for 2-3 years and EBRT of 46 Gy/23# to pelvic lymph nodes; plus prostate boost to 78 Gy/39#

OR

Group B: Identical placebo TID for 3 years total, with Neoadjuvant and adjuvant ADT for 2-3 years and EBRT of 46 Gy/23# to pelvic lymph nodes; plus prostate boost to 78 Gy/39#

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males ≥ 18 years of age
  2. Pathologically confirmed adenocarcinoma of the prostate with 1 or more of the following high risk features

    1. Any T3
    2. Gleason score ≥ 8.0, or
    3. PSA ≥ 20 ng/mL
  3. Normoglycemic or impaired Fasting Glucose defined as:

    1. Fasting Plasma Glucose of ≤ 6.9; or
    2. Plasma Glucose level of 11.0 mmol/L 2 hours following a 75 g oral glucose load; or
    3. HbA1c of < 6.4%
  4. Deemed fit to undergo curative intent external beam radiation therapy with concurrent androgen deprivation therapy by their attending radiation oncologist
  5. Accessible for follow-up clinical and laboratory assessments

Exclusion Criteria:

  1. Patients with evidence (either by imaging or pathology) of distant metastatic spread of their disease
  2. PSA ≥ 100
  3. Patients that meet ≥ 1 of the Canadian Diabetes Association criteria for the diagnosis of diabetes:

    1. Fasting Plasma Glucose of ≥ 7.0 mmol/L; or
    2. HBA 1c of 6.5%; or
    3. Plasma Glucose level of ≥ 11.1 mmol/L 2 hours following a 75 g oral glucose load; or
    4. Random Plasma Glucose level of ≥ 11.1 mmol/L
  4. Patient who currently take Metformin or those who have taken Metformin within the past 12 months
  5. History of lactic acidosis or conditions that predispose to lactic acidosis including:

    a. Impaired Renal Function (eGFR < 45); or b. Liver disease, including alcoholic liver disease, as demonstrated by any of the following parameters: i. AST > 1.8x the upper limit of normal ii. ALT > 1.8x 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

  6. Patients with prior bilateral orchiectomy
  7. Patients with prior prostatectomy
  8. Patients who are unable to provide informed consent
  9. 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).
  10. Patients on hormonal therapy for more than 3 months prior to registration in the trial

    -

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01996696

Contacts
Contact: Nawaid Usmani, MD 780-432-8518 Nawaid.usmani@albertahealthservices.ca

Locations
Canada, Alberta
Cross Cancer Institute Not yet recruiting
Edmonton, Alberta, Canada, T6G 1Z2
Contact: Nawaid Usmani, MD    780-432-8518    Nawaid.usmani@albertahealthservices.ca   
Sponsors and Collaborators
AHS Cancer Control Alberta
Investigators
Principal Investigator: Nawaid Usmani, MD Cross Cancer Institute
  More Information

No publications provided

Responsible Party: AHS Cancer Control Alberta
ClinicalTrials.gov Identifier: NCT01996696     History of Changes
Other Study ID Numbers: CCI-Usmani-01
Study First Received: November 22, 2013
Last Updated: December 4, 2013
Health Authority: Canada: Health Canada
United States: Food and Drug Administration

Keywords provided by AHS Cancer Control Alberta:
metformin
metabolic syndrome
weight gain

Additional relevant MeSH terms:
Neoplasms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Prostatic Diseases
Metabolic Syndrome X
Genital Diseases, Male
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 01, 2014