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Prostatic NeoplasmPhase 2PREMIUMNCT01996696

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

A Phase 2 study testing Metformin in people with Prostatic Neoplasm, run by AHS Cancer Control Alberta at 3 sites in Canada.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostatic Neoplasm
What is being tested?
Metformin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
83 participants
Where
3 sitesCanada
Study dates
Sep 2014to Nov 2020
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
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  • 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.
  • -

Trial locations and contacts

3 sites in 1 country.

Canada3 sites

  • Prairie Mountain Health - Western Manitoba Cancer Centre

    Brandon, Manitoba, R7A2B3

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

About this study

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.

Read the 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.

Being tested
Metformin, Placebo
Keywords
metformin, metabolic syndrome, weight gain
Medical subject headings
Prostatic Neoplasms, Metabolic Syndrome, Weight Gain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MetforminDrug

    Also called Fortamet, Glucophage, Glucophage XR, Glumetza

    Metformin 500 mg PO TID x 30-36 months

  • PlaceboDrug

    Identical placebo TID x 30-36 months

Study groups in NCT01996696
Study groupRoleWhat they receive
MetforminExperimentalMetformin 500 mg PO TID x 30-36 months
Receives: Drug: Metformin
PlaceboPlacebo comparatorIdentical placebo TID x 30-36 months
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mean body weight at 12 months of follow-up

    Measured: 12 months of follow-up

Secondary outcomes (1)

  1. Prevalence and incidence of Metabolic Syndrome

    Measured: At 6, 12, 24 and 36 months follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Nov 2013 (estimated)
  2. Study startSep 2014
  3. Primary completionNov 2020
  4. Study completionNov 2020

Why it stopped: Results of interim analysis indicate no statistically significant difference in the primary objective between the two arms at baseline and 12 months of follow-up.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
83 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01996696
Sponsor's protocol ID
CCI-Usmani-01
Acronym
PREMIUM
Status last verified
Jan 2024
First submitted
22 Nov 2013
Last updated
30 Jan 2024
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Metformin in people with Prostatic Neoplasm, run by AHS Cancer Control Alberta at 3 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 30 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Results of interim analysis indicate no statistically significant difference in the primary objective between the two arms at baseline and 12 months of follow-up.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean body weight at 12 months of follow-up (time frame: 12 months of follow-up). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01996696.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2024.

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