<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/NCT01677897</url>
  </required_header>
  <id_info>
    <org_study_id>MetAb-Pro</org_study_id>
    <nct_id>NCT01677897</nct_id>
  </id_info>
  <brief_title>Impact of the Addition of Metformin to Abiraterone in Metastatic Prostate Cancer Patients</brief_title>
  <acronym>MetAb-Pro</acronym>
  <official_title>Impact of the Addition of Metformin to Abiraterone in Pre-docetaxel Metastatic Castration-resistant Prostate Cancer Patients Progressing on Abiraterone Treatment (MetAb-Pro): a Phase II Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kantonsspital Graubünden</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Janssen-Cilag Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Kantonsspital Graubünden</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess the impact of the addition of metformin to abiraterone&#xD;
      on survival in patients with metastatic prostate cancer&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this study is to assess the impact of the addition of metformin to abiraterone&#xD;
      on survival in patients with metastatic chemotherapy-naive prostate cancer&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2013</start_date>
  <completion_date type="Actual">June 2018</completion_date>
  <primary_completion_date type="Actual">December 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>progression free survival</measure>
    <time_frame>at 12 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>overall survival</measure>
    <time_frame>up to 2 years</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>progression free survival at 24 weeks</measure>
    <time_frame>at 24 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>progression free survival</measure>
    <time_frame>up to 24 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>psa response</measure>
    <time_frame>at 12 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>number of adverse events according to the NCI CTCAE v4.0</measure>
    <time_frame>up to 24 weeks</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Metastatic Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Metformin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Metformin 2x1000mg orally per day</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>Adding Metformin to Abiraterone in case of PSA-Progression</description>
    <arm_group_label>Metformin</arm_group_label>
    <other_name>Abiraterone</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Metastatic adenocarcinoma of the prostate.&#xD;
&#xD;
          -  Patient must give written informed consent before registration.&#xD;
&#xD;
          -  Age ≥18 years.&#xD;
&#xD;
          -  WHO performance status 0-2.&#xD;
&#xD;
          -  Tumor progression (as defined below) after at least 1 hormonal treatment (orchiectomy,&#xD;
             LHRH agonist) with documented total testosterone levels ≤ 1.7 nmol/L (≤ 50 ng/dL).&#xD;
             Ongoing concurrent use of LHRH agonist is required if the patient has not been&#xD;
             surgically castrated.&#xD;
&#xD;
          -  PSA progression during treatment with abiraterone (at least 12 weeks of treatment)&#xD;
             defined as follows:&#xD;
&#xD;
               -  In case PSA levels had not decreased under treatment: ≥ 25% increase over&#xD;
                  baseline (at registration) AND an increase in the absolute PSA value of ≥ 5&#xD;
                  ng/mL.&#xD;
&#xD;
               -  In case of PSA response &lt; 50% under treatment: ≥ 25% increase over the nadir AND&#xD;
                  an increase in the absolute PSA value of ≥ 5 ng/mL.&#xD;
&#xD;
               -  In case of PSA response ≥ 50% under treatment: ≥ 50% increase over the nadir AND&#xD;
                  an increase in the absolute PSA value of ≥ 5 ng/mL Note: PSA progression has to&#xD;
                  be confirmed at least 1 week later. In case of confirmation the first date of PSA&#xD;
                  rise is relevant for the calculation.&#xD;
&#xD;
          -  Serum potassium ≥ 3.5mmol/L.&#xD;
&#xD;
          -  Adequate hematological values: neutrophils ≥1.5x109/L, platelets ≥100x109/L.&#xD;
&#xD;
          -  Adequate hepatic function: bilirubin ≤1.5 x ULN, ALT ≤2.5 x ULN.&#xD;
&#xD;
          -  Adequate renal function (calculated creatinine clearance ≥50 mL/min, according to the&#xD;
             formula of Cockcroft-Gault).&#xD;
&#xD;
          -  Able to swallow study drug as whole tablet.&#xD;
&#xD;
          -  Patient compliance and geographic proximity allow proper staging and follow-up.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous malignancy within 2 years with the exception of localized non-melanoma skin&#xD;
             cancer and Ta and Tis bladder cancer.&#xD;
&#xD;
          -  Known CNS or spinal cord metastases.&#xD;
&#xD;
          -  Active autoimmune disease requiring higher doses of corticosteroid than the equivalent&#xD;
             of prednisone 10mg/d.&#xD;
&#xD;
          -  Radiotherapy within the last 2 weeks before start of the trial treatment.&#xD;
&#xD;
          -  Patients treated with anti-androgens such as flutamide or bicalutamide, if not&#xD;
             discontinued at least 4 weeks prior to registration in case of response or in case of&#xD;
             no response 2 weeks prior to inclusion for wash-out reasons.&#xD;
&#xD;
          -  Prior treatment with metformin Prior treatment with metformin&#xD;
&#xD;
          -  Diabetic ketoacidosis, diabetic coma and precoma&#xD;
&#xD;
          -  Concurrent treatment with other experimental drugs or other anti-cancer therapy,&#xD;
             treatment in a clinical trial within 30 days prior to trial entry, except treatment&#xD;
             with bisphosphonates and LHRH agonists.&#xD;
&#xD;
          -  Known hypersensitivity to trial drugs or hypersensitivity to any of their components.&#xD;
&#xD;
          -  Concomitant drugs contraindicated for use with the trial drugs according to the&#xD;
             Swissmedic-approved product information.&#xD;
&#xD;
          -  Uncontrolled hypertension, history of cardiac failure NYHA class III or IV.&#xD;
&#xD;
          -  Serious underlying medical condition (at the judgment of the investigator) which could&#xD;
             impair the ability of the patient to participate in the trial (e.g. uncontrolled or&#xD;
             acute severe infection, uncontrolled diabetes).&#xD;
&#xD;
          -  Active or symptomatic viral hepatitis or chronic liver disease.&#xD;
&#xD;
          -  History of pituitary or adrenal dysfunction.&#xD;
&#xD;
          -  Gastrointestinal disorder affecting absorption.&#xD;
&#xD;
          -  Psychiatric disorder precluding understanding of information on trial related topics,&#xD;
             giving informed consent, or interfering with compliance for oral drug intake.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>michael mark, md</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kantonsspital Graubünden</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Kantonsspital Graubünden</name>
      <address>
        <city>Chur</city>
        <state>Graubünden</state>
        <zip>7000</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>August 28, 2012</study_first_submitted>
  <study_first_submitted_qc>August 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2012</study_first_posted>
  <last_update_submitted>March 3, 2019</last_update_submitted>
  <last_update_submitted_qc>March 3, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 5, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Kantonsspital Graubünden</investigator_affiliation>
    <investigator_full_name>Michael Mark</investigator_full_name>
    <investigator_title>assistant medical director</investigator_title>
  </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/NCT01677897
org study id: MetAb-Pro
nct id: NCT01677897
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this study is to assess the impact of the addition of metformin to abiraterone
      on survival in patients with metastatic prostate cancer
The purpose of this study is to assess the impact of the addition of metformin to abiraterone
      on survival in patients with metastatic chemotherapy-naive prostate cancer
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: progression free survival
time frame: at 12 weeks
measure: overall survival
time frame: up to 2 years
measure: progression free survival at 24 weeks
time frame: at 24 weeks
measure: progression free survival
time frame: up to 24 weeks
measure: psa response
time frame: at 12 weeks
measure: number of adverse events according to the NCI CTCAE v4.0
time frame: up to 24 weeks
arm group label: Metformin
arm group type: Experimental
description: Metformin 2x1000mg orally per day
intervention type: Drug
intervention name: Metformin
description: Adding Metformin to Abiraterone in case of PSA-Progression
arm group label: Metformin
other name: Abiraterone
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: michael mark, md
role: Principal Investigator
affiliation: Kantonsspital Graubünden
facility: 
country: Switzerland
responsible party type: Principal Investigator
investigator affiliation: Kantonsspital Graubünden
investigator full name: Michael Mark
investigator title: assistant medical director
mesh term: Prostatic Neoplasms
mesh term: Metformin