<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01733836</url>
  </required_header>
  <id_info>
    <org_study_id>MAS_001</org_study_id>
    <nct_id>NCT01733836</nct_id>
  </id_info>
  <brief_title>Prostate Cancer Active Surveillance Metformin Trial</brief_title>
  <official_title>A Randomized Double Blind Placebo Controlled Single Institution Phase 2 Study of Metformin in Patients Undergoing Active Surveillance for Prostate Cancer.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Health Network, Toronto</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Health Network, Toronto</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To determine whether the use of metformin in patients with low-risk prostate cancer can delay&#xD;
      progression to clinically significant prostate cancer.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    The reason for this decision is that this study is being merged with a larger multi-centre&#xD;
    study using the same agent in the same population.&#xD;
  </why_stopped>
  <start_date>January 2013</start_date>
  <completion_date type="Anticipated">October 2014</completion_date>
  <primary_completion_date type="Anticipated">October 2014</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Primary Clinical Outcome - Inhibition of Prostate Cancer</measure>
    <time_frame>18 months</time_frame>
    <description>To assess the role of metformin on the inhibition of low-risk localized prostate cancer progression in men undergoing active surveillance for prostate cancer.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Primary Scientific Endpoint - ki67 index</measure>
    <time_frame>18 months</time_frame>
    <description>To assess the effect of metformin on the cell cycle proliferation indices (ki67 index).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Secondary Endpoint - Cell Cycle Proliferation (CCP) Score</measure>
    <time_frame>18 months</time_frame>
    <description>To assess the effect of metformin on the cell cycle proliferation indices (CCP score)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Endpoint - Mechanism of Action</measure>
    <time_frame>18 months</time_frame>
    <description>To assess the effect of metformin on systemic and local signalling axes and morphometric measurements relevant to its mechanism of action.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary endpoint - Quality of Life</measure>
    <time_frame>18 months</time_frame>
    <description>To assess the impact of metformin on Quality of Life (QoL) indices.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Endpoint - Prognostic Panel</measure>
    <time_frame>18 months</time_frame>
    <description>To determine the utility of a prognostic panel of 31 cell cycle progression genes recently validated in prostate cancer.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Metformin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>850mg BID</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <arm_group_label>Metformin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Willing and able to provide informed consent&#xD;
&#xD;
          -  Men &gt;= 18 years of age, and less than 80&#xD;
&#xD;
          -  Men with biopsy proven, low-risk, localized prostate cancer (as defined below)&#xD;
&#xD;
          -  Men choosing expectant management as primary treatment for prostate cancer&#xD;
&#xD;
          -  Diagnostic biopsy performed within 4 months of screening visit&#xD;
&#xD;
          -  Gleason score ≤ 6 in 3 cores or less with no Gleason pattern 4, less than 50% of any&#xD;
             core involved in cancer&#xD;
&#xD;
          -  Clinical stage T1c-T2a (Initial diagnosis of T1a/T1b obtained during a TURP is not&#xD;
             allowed)&#xD;
&#xD;
          -  Serum PSA ≤10 ng/mL&#xD;
&#xD;
          -  Life expectancy greater than 5 years&#xD;
&#xD;
          -  Normal kidney and hepatic function as defined by the following criteria:&#xD;
&#xD;
               -  Total bilirubin less than 1.5 X institutional upper limit of normal (ULN)&#xD;
&#xD;
               -  AST (SGOT)/ALT(SGPT) less than 1.5 X institutional ULN&#xD;
&#xD;
               -  Alkaline phosphatase less than 2 X institutional ULN&#xD;
&#xD;
               -  Creatinine less than 1.4 X institutional ULN&#xD;
&#xD;
          -  Able to swallow and retain oral medication&#xD;
&#xD;
          -  No exposure to metformin within 12 months of randomization&#xD;
&#xD;
          -  No known hypersensitivity or intolerance to metformin hydrochloride&#xD;
&#xD;
          -  No condition associated with increased risk of metformin hydrochloride-associated&#xD;
             lactic acidosis (e.g., congestive heart failure defined as NYHA class III or IV&#xD;
             function status, history of acidosis of any type, or habitual intake of ≥ 3 alcoholic&#xD;
             beverages per day, or age greater than 80)&#xD;
&#xD;
          -  English fluency allowing for patient reported outcomes completion&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any previous prostate cancer treatment (radiotherapy, chemotherapy, hormonal therapy,&#xD;
             oral glucocorticoids, GnRH analogues)&#xD;
&#xD;
          -  Diabetes including type 1 diabetes. Patients with known type 2 diabetes are eligible&#xD;
             provided they have not been on metformin during the previous 12 months and are not on&#xD;
             any other pharmacological agents.&#xD;
&#xD;
          -  Concurrent or previous use of anabolic steroids or drugs with anti androgenic&#xD;
             properties including 5-ARIs (dutasteride and finasteride)&#xD;
&#xD;
          -  Prostate volume greater than 80 cc. (as per TRUS biopsy report)&#xD;
&#xD;
          -  Prostatic surgery or procedure within 3 months of screening visit&#xD;
&#xD;
          -  Severe BPH symptoms (IPSS ≥25, or ≥20 if already on α-blocker therapy)&#xD;
&#xD;
          -  Other malignancies, with the exception of adequately treated nonmelanoma skin cancer,&#xD;
             NMIBC or other solid tumors curatively treated with no evidence of disease for ≥ 5&#xD;
             years&#xD;
&#xD;
          -  Planned or concurrent participation in other interventional randomized trials&#xD;
             including exercise&#xD;
&#xD;
          -  The presence of any other coexistent medical condition that in the opinion of the&#xD;
             investigator would have the potential to significantly limit adherence to medication,&#xD;
             or ability to absorb the medication including but not limited to psychiatric&#xD;
             conditions, malabsorption syndromes or severe ischemic heart disease&#xD;
&#xD;
          -  Known hypersensitivity or intolerance to metformin&#xD;
&#xD;
          -  Concurrent or planned participation in randomized trials of weight loss or exercise&#xD;
             interventions or trials targeting insulin, IGF-1 or their receptors, or PI3K&#xD;
             inhibitors.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University Health Network</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>May 2013</verification_date>
  <study_first_submitted>November 20, 2012</study_first_submitted>
  <study_first_submitted_qc>November 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 27, 2012</study_first_posted>
  <last_update_submitted>May 23, 2013</last_update_submitted>
  <last_update_submitted_qc>May 23, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 24, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01733836
org study id: MAS_001
nct id: NCT01733836
lead sponsor: 
has dmc: Yes
To determine whether the use of metformin in patients with low-risk prostate cancer can delay
      progression to clinically significant prostate cancer.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Primary Clinical Outcome - Inhibition of Prostate Cancer
time frame: 18 months
description: To assess the role of metformin on the inhibition of low-risk localized prostate cancer progression in men undergoing active surveillance for prostate cancer.
measure: Primary Scientific Endpoint - ki67 index
time frame: 18 months
description: To assess the effect of metformin on the cell cycle proliferation indices (ki67 index).
measure: Secondary Endpoint - Cell Cycle Proliferation (CCP) Score
time frame: 18 months
description: To assess the effect of metformin on the cell cycle proliferation indices (CCP score)
measure: Secondary Endpoint - Mechanism of Action
time frame: 18 months
description: To assess the effect of metformin on systemic and local signalling axes and morphometric measurements relevant to its mechanism of action.
measure: Secondary endpoint - Quality of Life
time frame: 18 months
description: To assess the impact of metformin on Quality of Life (QoL) indices.
measure: Secondary Endpoint - Prognostic Panel
time frame: 18 months
description: To determine the utility of a prognostic panel of 31 cell cycle progression genes recently validated in prostate cancer.
arm group label: Metformin
arm group type: Experimental
description: 850mg BID
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Metformin
arm group label: Metformin
intervention type: Drug
intervention name: placebo
arm group label: Placebo
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Metformin