<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/NCT03024580</url>
  </required_header>
  <id_info>
    <org_study_id>64/16</org_study_id>
    <nct_id>NCT03024580</nct_id>
  </id_info>
  <brief_title>A Study Evaluating Megestrol Acetate Modulation in Hormone Receptor Positive Advanced Breast Cancer</brief_title>
  <acronym>MEGA</acronym>
  <official_title>A Pilot Study Evaluating Megestrol Acetate Modulation in Advanced Breast Cancer With Positive Hormonal Receptor</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Instituto Nacional de Cancer, Brazil</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cancer Research UK Cambridge Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Instituto Nacional de Cancer, Brazil</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This pilot trial evaluates in vivo megestrol acetate (MA) modulation of steroidal receptors&#xD;
      in advanced breast cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Progesterone receptor (PR) expression has been considered a biomarker of oestrogen receptor-α&#xD;
      (ERα) activity. This longstanding relationship has been recently challenged and instead of&#xD;
      being merely an ERα-induced gene target, PR may be a critical determinant of ERα activity.&#xD;
      The functional significance of this steroid receptor crosstalk is regulation of a gene&#xD;
      expression program associated with low tumorigenicity; hence, better disease outcome. Genomic&#xD;
      alterations in the PR genomic locus seem to be a relatively common mechanism for reduction of&#xD;
      PR expression, which may consequently lead to altered ERα chromatin binding and target gene&#xD;
      expression patterns that increase breast tumorigenicity and confers a poor clinical outcome.&#xD;
      This ERα-PR crosstalk may be directly influenced by many variables, including the relative&#xD;
      receptor levels and the hormonal milieu.&#xD;
&#xD;
      ER-positive advanced breast cancer is a heterogeneous group of diseases with considerable&#xD;
      variability in outcome to a range of treatments. Prior response predicts the likelihood of&#xD;
      subsequent benefit from another endocrine agent and this should be taken into account in the&#xD;
      treatment decision process when assessing whether to prescribe a subsequent endocrine&#xD;
      therapy. Despite the enormous progress made regarding the elucidation of breast cancer&#xD;
      subgroups and their molecular drivers, most information comes from primary tumors. MA lacks&#xD;
      cross-resistance and is active after acquired resistance to potent AI. This pilot trial&#xD;
      evaluates in vivo MA modulation of steroidal receptors in advanced breast cancer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 6, 2017</start_date>
  <completion_date type="Anticipated">September 2020</completion_date>
  <primary_completion_date type="Anticipated">March 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel 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>From date of randomization until disease progression or death due to any cause, assessed up to 18 months</time_frame>
    <description>From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From date of randomization until death, assessed up to 18 months</time_frame>
    <description>From date of randomization until the date of death from any cause, assessed up to 18 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical benefit</measure>
    <time_frame>Partial response and stable disease for more than 24 weeks, assessed up to 18 months</time_frame>
    <description>Partial response and stable disease for more than 24 weeks, as per RECIST criteria, from date of randomization until the date of first documented progression or date of death, whichever came first, assessed up to 18 months</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Breast Neoplasm</condition>
  <arm_group>
    <arm_group_label>Megestrol acetate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Megestrol acetate 160 mg PO daily until disease progression or unacceptable toxicity Tumor biopsy and blood collection before treatment initiation and at the time of disease progression.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Anastrozole</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Anastrozole 1 mg PO daily until disease progression or unacceptable toxicity Tumor biopsy and blood collection before treatment initiation and at the time of disease progression.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Letrozole</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Letrozole 2.5 mg PO daily until disease progression or unacceptable toxicity Tumor biopsy and blood collection before treatment initiation and at the time of disease progression.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Exemestane</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Exemestane 25 mg PO daily until disease progression or unacceptable toxicity Tumor biopsy and blood collection before treatment initiation and at the time of disease progression.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tamoxifen</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Tamoxifen 20 mg PO daily until disease progression or unacceptable toxicity Tumor biopsy and blood collection before treatment initiation and at the time of disease progression.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fulvestrant</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Fulvestrant 500 mg intramuscularly (IM) d1, d14, d28 and q28 days until disease progression or unacceptable toxicity Tumor biopsy and blood collection before treatment initiation and at the time of disease progression.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Megestrol Acetate 160Mg Tablet</intervention_name>
    <description>Megestrol acetate 160 mg PO daily</description>
    <arm_group_label>Megestrol acetate</arm_group_label>
    <other_name>MA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anastrozole 1Mg Tablet</intervention_name>
    <description>Anastrozole 1 mg PO daily OR</description>
    <arm_group_label>Anastrozole</arm_group_label>
    <other_name>Anastrozole</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Letrozole 2.5Mg Tablet</intervention_name>
    <description>Letrozole 2.5 mg PO daily OR</description>
    <arm_group_label>Letrozole</arm_group_label>
    <other_name>Letrozole</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Exemestane 25 MG</intervention_name>
    <description>Exemestane 25 mg PO daily</description>
    <arm_group_label>Exemestane</arm_group_label>
    <other_name>Exemestane</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tamoxifen 20Mg Tablet</intervention_name>
    <description>Tamoxifen 20 mg PO daily</description>
    <arm_group_label>Tamoxifen</arm_group_label>
    <other_name>Tamoxifen</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fulvestrant 50Mg Solution for Injection</intervention_name>
    <description>Fulvestrant 500 mg IM d1, d14, d28 and q28 days</description>
    <arm_group_label>Fulvestrant</arm_group_label>
    <other_name>Fulvestrant</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Metastatic breast cancer with ER and/or PR positive (primary tumor)&#xD;
&#xD;
          -  Metastatic site amenable to biopsy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Platelet count below 100,000 / mm3&#xD;
&#xD;
          -  Renal or hepatic impairment&#xD;
&#xD;
          -  Coagulation disorder&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>José Bines, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Instituto Nacional de Cancer, Brazil</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jason Carroll, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Cancer Research UK Cambridge Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Renata Obadia, RN</last_name>
    <phone>552132073810</phone>
    <email>robadia@inca.gov.br</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hospital do Cancer III</name>
      <address>
        <city>Rio de Janeiro</city>
        <zip>20560120</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Renata Obadia, RN</last_name>
      <phone>552132073810</phone>
      <email>robadia@inca.gov.br</email>
    </contact>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>January 4, 2017</study_first_submitted>
  <study_first_submitted_qc>January 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 19, 2017</study_first_posted>
  <last_update_submitted>August 14, 2019</last_update_submitted>
  <last_update_submitted_qc>August 14, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 15, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Megestrol Acetate</keyword>
  <keyword>Steroid, Receptors</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tamoxifen</mesh_term>
    <mesh_term>Letrozole</mesh_term>
    <mesh_term>Fulvestrant</mesh_term>
    <mesh_term>Anastrozole</mesh_term>
    <mesh_term>Exemestane</mesh_term>
    <mesh_term>Megestrol</mesh_term>
    <mesh_term>Megestrol Acetate</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/NCT03024580
org study id: 64/16
nct id: NCT03024580
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This pilot trial evaluates in vivo megestrol acetate (MA) modulation of steroidal receptors
      in advanced breast cancer.
Progesterone receptor (PR) expression has been considered a biomarker of oestrogen receptor-α
      (ERα) activity. This longstanding relationship has been recently challenged and instead of
      being merely an ERα-induced gene target, PR may be a critical determinant of ERα activity.
      The functional significance of this steroid receptor crosstalk is regulation of a gene
      expression program associated with low tumorigenicity; hence, better disease outcome. Genomic
      alterations in the PR genomic locus seem to be a relatively common mechanism for reduction of
      PR expression, which may consequently lead to altered ERα chromatin binding and target gene
      expression patterns that increase breast tumorigenicity and confers a poor clinical outcome.
      This ERα-PR crosstalk may be directly influenced by many variables, including the relative
      receptor levels and the hormonal milieu.

      ER-positive advanced breast cancer is a heterogeneous group of diseases with considerable
      variability in outcome to a range of treatments. Prior response predicts the likelihood of
      subsequent benefit from another endocrine agent and this should be taken into account in the
      treatment decision process when assessing whether to prescribe a subsequent endocrine
      therapy. Despite the enormous progress made regarding the elucidation of breast cancer
      subgroups and their molecular drivers, most information comes from primary tumors. MA lacks
      cross-resistance and is active after acquired resistance to potent AI. This pilot trial
      evaluates in vivo MA modulation of steroidal receptors in advanced breast cancer.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression free survival
time frame: From date of randomization until disease progression or death due to any cause, assessed up to 18 months
description: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months
measure: Overall survival
time frame: From date of randomization until death, assessed up to 18 months
description: From date of randomization until the date of death from any cause, assessed up to 18 months
measure: Clinical benefit
time frame: Partial response and stable disease for more than 24 weeks, assessed up to 18 months
description: Partial response and stable disease for more than 24 weeks, as per RECIST criteria, from date of randomization until the date of first documented progression or date of death, whichever came first, assessed up to 18 months
arm group label: Megestrol acetate
arm group type: Experimental
description: Megestrol acetate 160 mg PO daily until disease progression or unacceptable toxicity Tumor biopsy and blood collection before treatment initiation and at the time of disease progression.
arm group label: Anastrozole
arm group type: Active Comparator
description: Anastrozole 1 mg PO daily until disease progression or unacceptable toxicity Tumor biopsy and blood collection before treatment initiation and at the time of disease progression.
arm group label: Letrozole
arm group type: Active Comparator
description: Letrozole 2.5 mg PO daily until disease progression or unacceptable toxicity Tumor biopsy and blood collection before treatment initiation and at the time of disease progression.
arm group label: Exemestane
arm group type: Active Comparator
description: Exemestane 25 mg PO daily until disease progression or unacceptable toxicity Tumor biopsy and blood collection before treatment initiation and at the time of disease progression.
arm group label: Tamoxifen
arm group type: Active Comparator
description: Tamoxifen 20 mg PO daily until disease progression or unacceptable toxicity Tumor biopsy and blood collection before treatment initiation and at the time of disease progression.
arm group label: Fulvestrant
arm group type: Active Comparator
description: Fulvestrant 500 mg intramuscularly (IM) d1, d14, d28 and q28 days until disease progression or unacceptable toxicity Tumor biopsy and blood collection before treatment initiation and at the time of disease progression.
intervention type: Drug
intervention name: Megestrol Acetate 160Mg Tablet
description: Megestrol acetate 160 mg PO daily
arm group label: Megestrol acetate
other name: MA
intervention type: Drug
intervention name: Anastrozole 1Mg Tablet
description: Anastrozole 1 mg PO daily OR
arm group label: Anastrozole
other name: Anastrozole
intervention type: Drug
intervention name: Letrozole 2.5Mg Tablet
description: Letrozole 2.5 mg PO daily OR
arm group label: Letrozole
other name: Letrozole
intervention type: Drug
intervention name: Exemestane 25 MG
description: Exemestane 25 mg PO daily
arm group label: Exemestane
other name: Exemestane
intervention type: Drug
intervention name: Tamoxifen 20Mg Tablet
description: Tamoxifen 20 mg PO daily
arm group label: Tamoxifen
other name: Tamoxifen
intervention type: Drug
intervention name: Fulvestrant 50Mg Solution for Injection
description: Fulvestrant 500 mg IM d1, d14, d28 and q28 days
arm group label: Fulvestrant
other name: Fulvestrant
criteria: 
gender: Female
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: José Bines, MD, PhD
role: Study Chair
affiliation: Instituto Nacional de Cancer, Brazil
last name: Jason Carroll, PhD
role: Study Chair
affiliation: Cancer Research UK Cambridge Institute
last name: Renata Obadia, RN
phone: 552132073810
email: robadia@inca.gov.br
facility: 
status: Recruiting
contact: 
country: Brazil
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Tamoxifen
mesh term: Letrozole
mesh term: Fulvestrant
mesh term: Anastrozole
mesh term: Exemestane
mesh term: Megestrol
mesh term: Megestrol Acetate
sharing ipd: No