<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/NCT02190838</url>
  </required_header>
  <id_info>
    <org_study_id>MMM-1</org_study_id>
    <nct_id>NCT02190838</nct_id>
  </id_info>
  <brief_title>Comparison of Melatonin or Metformin and Dacarbazine Combination Versus Dacarbazine Alone in Disseminated Melanoma</brief_title>
  <official_title>Phase II Multicenter Randomized Study to Compare Dacarbazine With Melatonin or Metformin Versus Dacarbazine in the First Line Therapy of Disseminated Melanoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>N.N. Petrov National Medical Research Center of Oncology</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>N.N. Petrov National Medical Research Center of Oncology</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Treatment of disseminated melanoma is still a difficult issue. Obvious achievements of recent&#xD;
      years proves efficacy of immunologic approachees in this field. The ability of melatonin and&#xD;
      metformin to decrease metabolic immunosuppression was shown in many experimental studies.&#xD;
      Some literature data confirm the possibility of increasing efficacy of melatonin with&#xD;
      dacarbazine (DTIC) and metformin with DTIC combinations. We hypothesized that this&#xD;
      combinations could be more effective than DTIC monotherapy in terms of response rate and time&#xD;
      to progression.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Preliminary terminated due to inefficacy&#xD;
  </why_stopped>
  <start_date type="Actual">April 2014</start_date>
  <completion_date type="Actual">December 31, 2018</completion_date>
  <primary_completion_date type="Actual">December 12, 2015</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Response Rate</measure>
    <time_frame>23 months after FPFV</time_frame>
    <description>Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. ORR is defined as the proportion of patients with a best overall response of complete response or partial response</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>23 months after FPFV</time_frame>
    <description>As per RECIST v1.1. progression-free survival (PFS) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse events (AE) incidence</measure>
    <time_frame>until 30 days after last patient treatment visit</time_frame>
    <description>Incidence of AE classified using NCI Common Terminology Criteria for AE v4</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metabolic Changes Incidence</measure>
    <time_frame>23 months after FPFV</time_frame>
    <description>Nutritional status will be assessed using Nutritional Risk Index (NRI), Subjective global assessment (SGA), and Body Mass Index (BMI) tools.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune system assessment</measure>
    <time_frame>23 months after FPFV</time_frame>
    <description>Following tests will be performed at baseline and each response assessment:&#xD;
Lymphocyte subpopulations detection&#xD;
Immunosuppressive factors measurements</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">57</enrollment>
  <condition>Melanoma</condition>
  <arm_group>
    <arm_group_label>Dacarbazine with Metformin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>32 patients will receive Dacarbazine 1000 mg/m^2 once every 28 days with Metformin 850 mg BID.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dacarbazine and Melatonin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>32 patients will receive Dacarbazine 1000 mg/m^2 once every 28 days with Melatonin 3 mg before sleep daily.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dacarbazine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>32 patients will receive Dacarbazine 1000 mg/m^2 once every 28 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>per os 850 mg BID</description>
    <arm_group_label>Dacarbazine with Metformin</arm_group_label>
    <other_name>Siofor® 850</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Melatonin</intervention_name>
    <description>per os 3 mg daily</description>
    <arm_group_label>Dacarbazine and Melatonin</arm_group_label>
    <other_name>Melaxen</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dacarbazine</intervention_name>
    <description>IV 1 hour 1000 mg/m^2 once in 28 days</description>
    <arm_group_label>Dacarbazine</arm_group_label>
    <arm_group_label>Dacarbazine and Melatonin</arm_group_label>
    <arm_group_label>Dacarbazine with Metformin</arm_group_label>
    <other_name>DTIC</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt;18.&#xD;
&#xD;
          -  Obtained Inform Consent&#xD;
&#xD;
          -  Morphologically confirmed disseminated Stage IV melanoma&#xD;
&#xD;
          -  Eastern Collaborative Oncology Group Performance Status Scale 0 - 2.&#xD;
&#xD;
          -  Expected survival &gt;3 month&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Evidence of active brain lesions (brain lesions after stereotaxic ray therapy allowed)&#xD;
&#xD;
          -  Evidence of liver and bone marrow clinically meaningful disfunction&#xD;
&#xD;
          -  Severe uncontrolled concomitant conditions and diseases&#xD;
&#xD;
          -  Pregnancy or lactation&#xD;
&#xD;
          -  Systemic therapy for disseminated melanoma&#xD;
&#xD;
          -  Second malignancy&#xD;
&#xD;
          -  Diabetes mellitus requiring drug therapy&#xD;
&#xD;
          -  Any condition preventing study participation by investigator opinion&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Aleksei V. Novik, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>N.N. Petrov Research Institute of Oncology</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Irina A. Baldueva, MD, PhD, DSc</last_name>
    <role>Study Director</role>
    <affiliation>N.N. Petrov Research Institute of Oncology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>N.N. Petrov Research Institute of Oncology Ambulatory Chemotherapy Department</name>
      <address>
        <city>St. Petersburg</city>
        <zip>197758</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>N.N. Petrov Research Institute of Oncology Chemotherapy and Innovative Technologies Department</name>
      <address>
        <city>St. Petersburg</city>
        <zip>197758</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>N.N. Petrov Research Institute of Oncology Clinical Diagnostic Department</name>
      <address>
        <city>St.Petersburg</city>
        <zip>191124</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>July 13, 2014</study_first_submitted>
  <study_first_submitted_qc>July 13, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 15, 2014</study_first_posted>
  <last_update_submitted>November 22, 2019</last_update_submitted>
  <last_update_submitted_qc>November 22, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 25, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Melanoma</keyword>
  <keyword>Melatonin</keyword>
  <keyword>Metformin</keyword>
  <keyword>Dacarbazine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
    <mesh_term>Dacarbazine</mesh_term>
    <mesh_term>Melatonin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02190838
org study id: MMM-1
nct id: NCT02190838
lead sponsor: 
has dmc: Yes
Treatment of disseminated melanoma is still a difficult issue. Obvious achievements of recent
      years proves efficacy of immunologic approachees in this field. The ability of melatonin and
      metformin to decrease metabolic immunosuppression was shown in many experimental studies.
      Some literature data confirm the possibility of increasing efficacy of melatonin with
      dacarbazine (DTIC) and metformin with DTIC combinations. We hypothesized that this
      combinations could be more effective than DTIC monotherapy in terms of response rate and time
      to progression.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Response Rate
time frame: 23 months after FPFV
description: Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. ORR is defined as the proportion of patients with a best overall response of complete response or partial response
measure: Progression Free Survival
time frame: 23 months after FPFV
description: As per RECIST v1.1. progression-free survival (PFS) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause.
measure: Adverse events (AE) incidence
time frame: until 30 days after last patient treatment visit
description: Incidence of AE classified using NCI Common Terminology Criteria for AE v4
measure: Metabolic Changes Incidence
time frame: 23 months after FPFV
description: Nutritional status will be assessed using Nutritional Risk Index (NRI), Subjective global assessment (SGA), and Body Mass Index (BMI) tools.
measure: Immune system assessment
time frame: 23 months after FPFV
description: Following tests will be performed at baseline and each response assessment:
Lymphocyte subpopulations detection
Immunosuppressive factors measurements
arm group label: Dacarbazine with Metformin
arm group type: Experimental
description: 32 patients will receive Dacarbazine 1000 mg/m^2 once every 28 days with Metformin 850 mg BID.
arm group label: Dacarbazine and Melatonin
arm group type: Experimental
description: 32 patients will receive Dacarbazine 1000 mg/m^2 once every 28 days with Melatonin 3 mg before sleep daily.
arm group label: Dacarbazine
arm group type: Active Comparator
description: 32 patients will receive Dacarbazine 1000 mg/m^2 once every 28 days
intervention type: Drug
intervention name: Metformin
description: per os 850 mg BID
arm group label: Dacarbazine with Metformin
other name: Siofor® 850
intervention type: Drug
intervention name: Melatonin
description: per os 3 mg daily
arm group label: Dacarbazine and Melatonin
other name: Melaxen
intervention type: Drug
intervention name: Dacarbazine
description: IV 1 hour 1000 mg/m^2 once in 28 days
arm group label: Dacarbazine
arm group label: Dacarbazine and Melatonin
arm group label: Dacarbazine with Metformin
other name: DTIC
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Aleksei V. Novik, MD, PhD
role: Principal Investigator
affiliation: N.N. Petrov Research Institute of Oncology
last name: Irina A. Baldueva, MD, PhD, DSc
role: Study Director
affiliation: N.N. Petrov Research Institute of Oncology
facility: 
facility: 
facility: 
country: Russian Federation
responsible party type: Sponsor
mesh term: Melanoma
mesh term: Metformin
mesh term: Dacarbazine
mesh term: Melatonin
sharing ipd: No