Back to resultsPrevention of Metabolic Syndrome and Increased Weight Using Metformin Concurrent to Androgen Deprivation Therapy and Radiotherapy for Locally Advanced Adenocarcinoma of the Prostate (PREMIUM)
Primary Purpose
Prostatic Neoplasm
Status
Unknown status
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Metformin
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Prostatic Neoplasm focused on measuring metformin, metabolic syndrome, weight gain
Eligibility Criteria
Inclusion Criteria:
- Males ≥ 18 years of age
Pathologically confirmed, adenocarcinoma of the prostate with either high-tier intermediate or high risk prostate cancer:
a. 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.
a. 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:
a. 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.
-
Sites / Locations
- Cross Cancer InstituteRecruiting
- Prairie Mountain Health - Western Manitoba Cancer CentreRecruiting
- CancerCare ManitobaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Metformin
Placebo
Arm Description
Metformin 500 mg PO TID x 30-36 months
Identical placebo TID x 30-36 months
Outcomes
Primary Outcome Measures
Mean body weight at 12 months of follow-up
Secondary Outcome Measures
Prevalence and incidence of Metabolic Syndrome
Full Information
NCT ID
NCT01996696
First Posted
November 22, 2013
Last Updated
July 2, 2019
Sponsor
AHS Cancer Control Alberta
1. Study Identification
Unique Protocol Identification Number
NCT01996696
Brief Title
Prevention of Metabolic Syndrome and Increased Weight Using Metformin Concurrent to Androgen Deprivation Therapy and Radiotherapy for Locally Advanced Adenocarcinoma of the Prostate
Acronym
PREMIUM
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 Type
Interventional
2. Study Status
Record Verification Date
July 2019
Overall Recruitment Status
Unknown status
Study Start Date
September 2014 (undefined)
Primary Completion Date
September 2021 (Anticipated)
Study Completion Date
September 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AHS Cancer Control Alberta
4. Oversight
Data Monitoring Committee
Yes
5. 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.
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
OR
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostatic Neoplasm
Keywords
metformin, metabolic syndrome, weight gain
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
104 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Metformin
Arm Type
Experimental
Arm Description
Metformin 500 mg PO TID x 30-36 months
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Identical placebo TID x 30-36 months
Intervention Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
Fortamet, Glucophage, Glucophage XR, Glumetza, Riomet
Intervention Description
Metformin 500 mg PO TID x 30-36 months
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Identical placebo TID x 30-36 months
Primary Outcome Measure Information:
Title
Mean body weight at 12 months of follow-up
Time Frame
12 months of follow-up
Secondary Outcome Measure Information:
Title
Prevalence and incidence of Metabolic Syndrome
Time Frame
At 6, 12, 24 and 36 months follow-up
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males ≥ 18 years of age
Pathologically confirmed, adenocarcinoma of the prostate with either high-tier intermediate or high risk prostate cancer:
a. 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.
a. 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:
a. 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.
-
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nawaid Usmani, MD
Phone
780-432-8518
Email
Nawaid.usmani@albertahealthservices.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nawaid Usmani, MD
Organizational Affiliation
Cross Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cross Cancer Institute
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nawaid Usmani, MD
Phone
780-432-8518
Email
Nawaid.usmani@albertahealthservices.ca
Facility Name
Prairie Mountain Health - Western Manitoba Cancer Centre
City
Brandon
State/Province
Manitoba
ZIP/Postal Code
R7A2B3
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joelle Dumontier
Phone
204-578-2108
Email
jdumontier@pmh-mb.ca
First Name & Middle Initial & Last Name & Degree
William Hunter, MD
Phone
204-578-2208
Email
whunter@cancercare.mb.ca
First Name & Middle Initial & Last Name & Degree
William Hunter, MD
Facility Name
CancerCare Manitoba
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3E 0V9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julian Kim, MD
Phone
204-787-4760
Email
jkim7@cancercare.mb.ca
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Prevention of Metabolic Syndrome and Increased Weight Using Metformin Concurrent to Androgen Deprivation Therapy and Radiotherapy for Locally Advanced Adenocarcinoma of the Prostate
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