<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/NCT03306472</url>
  </required_header>
  <id_info>
    <org_study_id>PIONEER</org_study_id>
    <secondary_id>2016-003752-79</secondary_id>
    <nct_id>NCT03306472</nct_id>
  </id_info>
  <brief_title>A Pre-operative Window Study of Letrozole Plus PR Agonist (Megestrol Acetate) Versus Letrozole Alone in Post-menopausal Patients With ER-positive Breast Cancer</brief_title>
  <acronym>PIONEER</acronym>
  <official_title>Randomised Phase II Clinical Trial PIONEER- A Pre-operative wIndOw Study of Letrozole Plus PR Agonist (Megestrol Acetate) Versus Letrozole aloNE in Post-menopausal Patients With ER-positive Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cambridge University Hospitals NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Anticancer Fund, Belgium</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Cambridge University Hospitals NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Around 75% of breast cancers are defined and driven by Oestrogen receptor alpha (ERα)&#xD;
      transcriptional activity. Standard treatment is endocrine therapy however clinical outcomes&#xD;
      vary considerably, and a proportion of women with early breast cancer driven by ERα&#xD;
      transcriptional activity develop drug resistance, and relapse with incurable, metastatic&#xD;
      disease.&#xD;
&#xD;
      Historically, PR-positivity was viewed as just a passive consequence of a functional&#xD;
      oestrogen receptor, and PR was established as a biomarker of ER functionality in breast&#xD;
      cancer. However, recent preclinical discoveries have provided an alternative explanation to&#xD;
      the previous over-simplistic assumption, providing new insights into progestogen action and&#xD;
      functional 'cross-talk' between ER and PR in breast cancer. In the presence of agonist&#xD;
      ligands, progesterone-activated PR causes rapid sequestration of ERa chromatin binding sites&#xD;
      in breast cancer cells, resulting in a unique gene expression program that is associated with&#xD;
      a good clinical outcomes. This highlights a potential therapeutic opportunity.&#xD;
&#xD;
      The PIONEER trial will investigate the effect of combining megestrol acetate (a progesterone&#xD;
      receptor agonist) and letrozole (an aromatase inhibitor) in post menopausal women with early&#xD;
      breast cancer. This is a 'window of opportunity' study treating and observing patients in the&#xD;
      two weeks prior to definitive surgery. Patients are randomised into one of three arms; one in&#xD;
      which the patients receive Letrozole alone; one in which they will receive a combination of&#xD;
      Letrozole and low dose Megestrol acetate and the third arm will receive Letrozole and high&#xD;
      dose Megestrol acetate. This trial will be open to postmenopausal women with newly diagnosed,&#xD;
      untreated ER-positive, HER2-negative, invasive primary breast cancer.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 20, 2017</start_date>
  <completion_date type="Anticipated">November 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">October 31, 2021</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>
    <intervention_model_description>This is a three arm, open-label, multicentre, randomized, window of opportunity, Phase II trial which will evaluate the effects of 15 days (+ 4 days) preoperative therapy with Letrozole, or Letrozole plus low dose Megestrol acetate (40mg), or Letrozole plus high dose Megestrol acetate (160mg) in postmenopausal women with newly diagnosed, ER-positive, HER2-negative, invasive primary breast cancer of at least 1 cm size.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Unblinded</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Determination of change in tumour proliferation measured by Ki67 immunohistochemical (IHC) assessment (%) at baseline compared to Day 15 (+ ≤4 days).</measure>
    <time_frame>Over 15 days of treatment with letrozole (alone or in combination with high or low dose megestrol acetate)</time_frame>
    <description>Tumour-cell Ki67 antigen labeling index will be recorded following the recommendations from the International Ki67 working group. Ki67 will be scored as the percentage of tumour nuclei staining. The investigators analyzing Ki67 will be blinded as to treatment allocation. Ki67-response is defined as a 50% or higher fall in Ki67 expression.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in tumour apoptosis, measured by Caspase 3 (IHC)</measure>
    <time_frame>Over 15 days of treatment with letrozole (alone or in combination with high or low dose megestrol acetate)</time_frame>
    <description>Caspase-3 is activated by cleavage in cells undergoing apoptosis. Capase-3 IHC has been validated as a marker of apoptosis in breast cancer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in expression of Androgen receptor and Progesterone receptor by IHC</measure>
    <time_frame>Over 15 days of treatment with letrozole (alone or in combination with high or low dose megestrol acetate)</time_frame>
    <description>IHC of PR will be performed as a surrogate of ER activity. IHC of AR will be performed as AR influences ER-alpha activity in breast cancer, and has been shown to be a predictor of response to other synthetic progestins in breast cancer. Both PR and AR levels will be correlated with Ki67 changes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in expression of Epithelial-Mesenchymal Transition (EMT) markers by IHC</measure>
    <time_frame>Over 15 days of treatment with letrozole (alone or in combination with high or low dose megestrol acetate)</time_frame>
    <description>IHC of epithelial markers E-Cadherin and Mesenchymal markers N-Cadherin, Fibronectin and Vimentin, to assess the effect of treatment on expression of genes validated to indicate risk of breast cancer progression and metastasis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in proliferation by Aurora Kinase A labeling by IHC</measure>
    <time_frame>Over 15 days of treatment with letrozole (alone or in combination with high or low dose megestrol acetate)</time_frame>
    <description>Aurora Kinase A by IHC was found to outperform other proliferation markers as an independent predictor of breast cancer specific survival in ER-positive breast cancer, and will be analysed alongside Ki67.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute value of Ki67 at day 15 (+≤4 Days)</measure>
    <time_frame>Over 15 days of treatment with letrozole (alone or in combination with high or low dose megestrol acetate)</time_frame>
    <description>Measured to inform the development of a larger adjuvant trial following PIONEER. The absolute value of Ki67 at Day 15 has been found to be better predictive of recurrence free survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and Severity of Adverse Events</measure>
    <time_frame>Over 15 days of treatment with letrozole (alone or in combination with high or low dose megestrol acetate)</time_frame>
    <description>Determine the incidence and severity of adverse events caused by 15 days of treatment with letrozole (either alone or in combination with low or high dose megestrol acetate) prior to breast surgery. The severity of adverse events will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v4.03).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Chromatin Immunoprecipitation followed by high throughput DNA Sequencing (ChIP-seq) of ER, conducted to assess progestin-induced ER reprogramming</measure>
    <time_frame>Over 15 days of treatment with letrozole (alone or in combination with high or low dose megestrol acetate)</time_frame>
    <description>ChIP-seq will allow demonstration of the robust and predictable ERα binding to novel genomic loci, mediated by PR.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in epithelial mesenchymal transition markers by IHC</measure>
    <time_frame>Over 15 days of treatment with letrozole (alone or in combination with high or low dose megestrol acetate)</time_frame>
    <description>To address the question of whether the combination of letrozole and megestrol acetate affects the metastatic potential of ER-positive breast cancer, IHC will be performed to compare the pre- and post-treatment cytoplasmic expression of E-cadherin and N-cadherin.</description>
  </other_outcome>
  <other_outcome>
    <measure>Correlate differences in response to treatments with breast cancer genomic profiling datasets</measure>
    <time_frame>Over 15 days of treatment with letrozole (alone or in combination with high or low dose megestrol acetate)</time_frame>
    <description>To delineate potential underlying germline, somatic and pharmacogenetic reasons for response/non-response to trial treatment.If available, whole genome sequencing data from patients consented and recruited to studies collecting this information may be referenced.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">189</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Arm A: Letrozole</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Arm A: 15 days of Letrozole 2.5mg daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B: Letrozole + Megestrol Acetate (40mg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm B: 15 days of Letrozole 2.5mg daily + Megestrol acetate 40mg daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm C: Letrozole + Megestrol Acetate (160mg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm C: 15 days of Letrozole 2.5mg daily + Megestrol acetate 160mg daily.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Megestrol Acetate 40 MG</intervention_name>
    <description>Progesterone Agonist</description>
    <arm_group_label>Arm B: Letrozole + Megestrol Acetate (40mg)</arm_group_label>
    <other_name>Megace</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Megestrol Acetate 160 MG</intervention_name>
    <description>Progesterone Agonist</description>
    <arm_group_label>Arm C: Letrozole + Megestrol Acetate (160mg)</arm_group_label>
    <other_name>Megace</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Letrozole</intervention_name>
    <description>Aromatase Inhibitor</description>
    <arm_group_label>Arm A: Letrozole</arm_group_label>
    <arm_group_label>Arm B: Letrozole + Megestrol Acetate (40mg)</arm_group_label>
    <arm_group_label>Arm C: Letrozole + Megestrol Acetate (160mg)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed breast adenocarcinoma&#xD;
&#xD;
          -  Postmenopausal women&#xD;
&#xD;
          -  Core biopsy confirmation of invasive carcinoma on core biopsy, ≥T1c, either clinical&#xD;
             NX or N0-N3&#xD;
&#xD;
          -  ER positive (Allred≥3) and HER2 negative&#xD;
&#xD;
          -  2 groups of patients are potentially eligible:&#xD;
&#xD;
               -  Cohort A: Patients whose cancers have been deemed to be operable by the&#xD;
                  Multi-Disciplinary Team (MDT), with surgery planned for the next 2-6 weeks&#xD;
&#xD;
               -  Cohort B: Patients with early or locoregionally advanced breast cancer planned&#xD;
                  for primary endocrine therapy, either in lieu of surgery or as neoadjuvant&#xD;
                  therapy prior to surgery- such patients must begin PIONEER trial therapy prior to&#xD;
                  starting any other endocrine therapy.&#xD;
&#xD;
          -  ECOG performance status of 0, 1 or 2&#xD;
&#xD;
          -  Adequate Liver, Renal and Bone marrow function, defined as:&#xD;
&#xD;
               -  Adequate liver function where bilirubin is ≤1.5 x ULN&#xD;
&#xD;
               -  Adequate renal function with serum creatinine ≤ 1.5 x ULN&#xD;
&#xD;
               -  Adequate bone marrow function with ANC ≥1.0 x 10*9/L and Platelet count ≥100 x&#xD;
                  10*9/L&#xD;
&#xD;
          -  Written informed consent to participate in the trial and to donation of tissue&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of hormone replacement therapy in the last 6 months&#xD;
&#xD;
          -  Previous treatment with Tamoxifen or an aromatase inhibitor in the last six months&#xD;
&#xD;
          -  Known hypersensitivity or contraindications to aromatase inhibitors or Megestrol&#xD;
             acetate&#xD;
&#xD;
          -  Known allergy to lactose&#xD;
&#xD;
          -  Known to have a progestogen-containing intrauterine system in situ, unless removed&#xD;
             prior to randomisation&#xD;
&#xD;
          -  Known metastatic disease on presentation&#xD;
&#xD;
          -  Recurrent breast cancer (patients with a new primary invasive breast cancer will be&#xD;
             eligible to participate)&#xD;
&#xD;
          -  Serious concomitant disorders that would compromise the safety of the patient or&#xD;
             compromise the patient's ability to complete the trial, at the discretion of the&#xD;
             investigator&#xD;
&#xD;
          -  Treatment with an investigational drug within 4 weeks before randomisation&#xD;
&#xD;
          -  Inability to swallow orally administered medication and patients with gastrointestinal&#xD;
             disorders likely to interfere with absorption of the trial medication&#xD;
&#xD;
          -  Inability to give informed consent&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Yes: Eligibility is based on gender. Patients must be genetically female.</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Richard Baird, MA MBBS PhD FRCP</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Angels Kateb Castellnou</last_name>
    <phone>01223 348073</phone>
    <phone_ext>348073</phone_ext>
    <email>angels.kateb@addenbrookes.nhs.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Louise Grybowicz</last_name>
    <phone>01223 348086</phone>
    <phone_ext>348086</phone_ext>
    <email>louise.grybowicz@addenbrookes.nhs.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Cambridge University Hospitals NHS Foundation Trust</name>
      <address>
        <city>Cambridge</city>
        <state>Cambridgeshire</state>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Angels Kateb Castellnou, BSc, MSc</last_name>
      <phone>01223 348073</phone>
      <email>angels.kateb@addenbrookes.nhs.uk</email>
    </contact>
    <contact_backup>
      <email>pioneer@addenbrookes.nhs.uk</email>
    </contact_backup>
    <investigator>
      <last_name>Richard Baird, MA MBBS PhD FRCP</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>May 26, 2017</study_first_submitted>
  <study_first_submitted_qc>October 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 11, 2017</study_first_posted>
  <last_update_submitted>January 12, 2021</last_update_submitted>
  <last_update_submitted_qc>January 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 13, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cambridge University Hospitals NHS Foundation Trust</investigator_affiliation>
    <investigator_full_name>Richard D. Baird MD PhD</investigator_full_name>
    <investigator_title>Honorary Consultant in Medical Oncology</investigator_title>
  </responsible_party>
  <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>Letrozole</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/NCT03306472
org study id: PIONEER
secondary id: 2016-003752-79
nct id: NCT03306472
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Around 75% of breast cancers are defined and driven by Oestrogen receptor alpha (ERα)
      transcriptional activity. Standard treatment is endocrine therapy however clinical outcomes
      vary considerably, and a proportion of women with early breast cancer driven by ERα
      transcriptional activity develop drug resistance, and relapse with incurable, metastatic
      disease.

      Historically, PR-positivity was viewed as just a passive consequence of a functional
      oestrogen receptor, and PR was established as a biomarker of ER functionality in breast
      cancer. However, recent preclinical discoveries have provided an alternative explanation to
      the previous over-simplistic assumption, providing new insights into progestogen action and
      functional 'cross-talk' between ER and PR in breast cancer. In the presence of agonist
      ligands, progesterone-activated PR causes rapid sequestration of ERa chromatin binding sites
      in breast cancer cells, resulting in a unique gene expression program that is associated with
      a good clinical outcomes. This highlights a potential therapeutic opportunity.

      The PIONEER trial will investigate the effect of combining megestrol acetate (a progesterone
      receptor agonist) and letrozole (an aromatase inhibitor) in post menopausal women with early
      breast cancer. This is a 'window of opportunity' study treating and observing patients in the
      two weeks prior to definitive surgery. Patients are randomised into one of three arms; one in
      which the patients receive Letrozole alone; one in which they will receive a combination of
      Letrozole and low dose Megestrol acetate and the third arm will receive Letrozole and high
      dose Megestrol acetate. This trial will be open to postmenopausal women with newly diagnosed,
      untreated ER-positive, HER2-negative, invasive primary breast cancer.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a three arm, open-label, multicentre, randomized, window of opportunity, Phase II trial which will evaluate the effects of 15 days (+ 4 days) preoperative therapy with Letrozole, or Letrozole plus low dose Megestrol acetate (40mg), or Letrozole plus high dose Megestrol acetate (160mg) in postmenopausal women with newly diagnosed, ER-positive, HER2-negative, invasive primary breast cancer of at least 1 cm size.
primary purpose: Treatment
masking: None (Open Label)
masking description: Unblinded
measure: Determination of change in tumour proliferation measured by Ki67 immunohistochemical (IHC) assessment (%) at baseline compared to Day 15 (+ ≤4 days).
time frame: Over 15 days of treatment with letrozole (alone or in combination with high or low dose megestrol acetate)
description: Tumour-cell Ki67 antigen labeling index will be recorded following the recommendations from the International Ki67 working group. Ki67 will be scored as the percentage of tumour nuclei staining. The investigators analyzing Ki67 will be blinded as to treatment allocation. Ki67-response is defined as a 50% or higher fall in Ki67 expression.
measure: Change in tumour apoptosis, measured by Caspase 3 (IHC)
time frame: Over 15 days of treatment with letrozole (alone or in combination with high or low dose megestrol acetate)
description: Caspase-3 is activated by cleavage in cells undergoing apoptosis. Capase-3 IHC has been validated as a marker of apoptosis in breast cancer.
measure: Change in expression of Androgen receptor and Progesterone receptor by IHC
time frame: Over 15 days of treatment with letrozole (alone or in combination with high or low dose megestrol acetate)
description: IHC of PR will be performed as a surrogate of ER activity. IHC of AR will be performed as AR influences ER-alpha activity in breast cancer, and has been shown to be a predictor of response to other synthetic progestins in breast cancer. Both PR and AR levels will be correlated with Ki67 changes
measure: Change in expression of Epithelial-Mesenchymal Transition (EMT) markers by IHC
time frame: Over 15 days of treatment with letrozole (alone or in combination with high or low dose megestrol acetate)
description: IHC of epithelial markers E-Cadherin and Mesenchymal markers N-Cadherin, Fibronectin and Vimentin, to assess the effect of treatment on expression of genes validated to indicate risk of breast cancer progression and metastasis
measure: Change in proliferation by Aurora Kinase A labeling by IHC
time frame: Over 15 days of treatment with letrozole (alone or in combination with high or low dose megestrol acetate)
description: Aurora Kinase A by IHC was found to outperform other proliferation markers as an independent predictor of breast cancer specific survival in ER-positive breast cancer, and will be analysed alongside Ki67.
measure: Absolute value of Ki67 at day 15 (+≤4 Days)
time frame: Over 15 days of treatment with letrozole (alone or in combination with high or low dose megestrol acetate)
description: Measured to inform the development of a larger adjuvant trial following PIONEER. The absolute value of Ki67 at Day 15 has been found to be better predictive of recurrence free survival
measure: Incidence and Severity of Adverse Events
time frame: Over 15 days of treatment with letrozole (alone or in combination with high or low dose megestrol acetate)
description: Determine the incidence and severity of adverse events caused by 15 days of treatment with letrozole (either alone or in combination with low or high dose megestrol acetate) prior to breast surgery. The severity of adverse events will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v4.03).
measure: Chromatin Immunoprecipitation followed by high throughput DNA Sequencing (ChIP-seq) of ER, conducted to assess progestin-induced ER reprogramming
time frame: Over 15 days of treatment with letrozole (alone or in combination with high or low dose megestrol acetate)
description: ChIP-seq will allow demonstration of the robust and predictable ERα binding to novel genomic loci, mediated by PR.
measure: Change in epithelial mesenchymal transition markers by IHC
time frame: Over 15 days of treatment with letrozole (alone or in combination with high or low dose megestrol acetate)
description: To address the question of whether the combination of letrozole and megestrol acetate affects the metastatic potential of ER-positive breast cancer, IHC will be performed to compare the pre- and post-treatment cytoplasmic expression of E-cadherin and N-cadherin.
measure: Correlate differences in response to treatments with breast cancer genomic profiling datasets
time frame: Over 15 days of treatment with letrozole (alone or in combination with high or low dose megestrol acetate)
description: To delineate potential underlying germline, somatic and pharmacogenetic reasons for response/non-response to trial treatment.If available, whole genome sequencing data from patients consented and recruited to studies collecting this information may be referenced.
arm group label: Arm A: Letrozole
arm group type: Active Comparator
description: Arm A: 15 days of Letrozole 2.5mg daily
arm group label: Arm B: Letrozole + Megestrol Acetate (40mg)
arm group type: Experimental
description: Arm B: 15 days of Letrozole 2.5mg daily + Megestrol acetate 40mg daily
arm group label: Arm C: Letrozole + Megestrol Acetate (160mg)
arm group type: Experimental
description: Arm C: 15 days of Letrozole 2.5mg daily + Megestrol acetate 160mg daily.
intervention type: Drug
intervention name: Megestrol Acetate 40 MG
description: Progesterone Agonist
arm group label: Arm B: Letrozole + Megestrol Acetate (40mg)
other name: Megace
intervention type: Drug
intervention name: Megestrol Acetate 160 MG
description: Progesterone Agonist
arm group label: Arm C: Letrozole + Megestrol Acetate (160mg)
other name: Megace
intervention type: Drug
intervention name: Letrozole
description: Aromatase Inhibitor
arm group label: Arm A: Letrozole
arm group label: Arm B: Letrozole + Megestrol Acetate (40mg)
arm group label: Arm C: Letrozole + Megestrol Acetate (160mg)
criteria: 
gender: Female
gender based: Yes
gender description: Yes: Eligibility is based on gender. Patients must be genetically female.
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Richard Baird, MA MBBS PhD FRCP
role: Principal Investigator
affiliation: Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge
last name: Angels Kateb Castellnou
phone: 01223 348073
phone ext: 348073
email: angels.kateb@addenbrookes.nhs.uk
last name: Louise Grybowicz
phone: 01223 348086
phone ext: 348086
email: louise.grybowicz@addenbrookes.nhs.uk
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United Kingdom
responsible party type: Principal Investigator
investigator affiliation: Cambridge University Hospitals NHS Foundation Trust
investigator full name: Richard D. Baird MD PhD
investigator title: Honorary Consultant in Medical Oncology
mesh term: Breast Neoplasms
mesh term: Letrozole
mesh term: Megestrol
mesh term: Megestrol Acetate
sharing ipd: No