<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/NCT03804944</url>
  </required_header>
  <id_info>
    <org_study_id>1808019498</org_study_id>
    <nct_id>NCT03804944</nct_id>
  </id_info>
  <brief_title>Converting HR+ Breast Cancer Into an Individualized Vaccine</brief_title>
  <acronym>CBCV</acronym>
  <official_title>Converting HR+ Breast Cancer Into an Individualized Vaccine</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Weill Medical College of Cornell University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>United States Department of Defense</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Celldex Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Weill Medical College of Cornell University</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Newly diagnosed post-menopausal women with clinical stage II-III, HR+HER2- breast cancer are&#xD;
      eligible to a randomized trial, concurrently open at five US academic institutions. Patients&#xD;
      receiving 4 months of standard neoadjuvant hormonal therapy with letrozole are randomly&#xD;
      assigned to one of 4 arms of a trial testing focal hypo-fractionated RT alone or with&#xD;
      immunotherapy combinations.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients will be on the study for a total of 5 months, this includes 4 months on active study&#xD;
      intervention, with breast surgery at week 16 and one month follow up period, after surgery.&#xD;
      Patients will be randomly assigned to one of these 4 arms - 1. Anti-PD1 antibody&#xD;
      pembrolizumab (Keytruda, Merck) will be infused day 12, at the standard dose of 200 mg IV&#xD;
      over 30 minutes, repeated every 3 weeks until disease progression or unacceptable toxicity.&#xD;
      2. FLT3L (CDX-301, the recombinant human protein by Celldex) will be self-administered&#xD;
      subcutaneously, in 5 consecutive daily injections, week 1, day 1-5. 3. For all arms radiation&#xD;
      therapy to the breast tumor will begin on week 2 (Day 8,10,12), at dose of 8 Gy x 3&#xD;
      fractions, every other day. 4. Letrozole (Femara ®, Novartis) 2.5 mg tabs, once a day, daily&#xD;
      for 4 months, until surgery, and thereafter is decided by the treating physician.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 17, 2020</start_date>
  <completion_date type="Anticipated">December 2027</completion_date>
  <primary_completion_date type="Anticipated">December 2025</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>Patients will be on the study for a total of 5 months, this includes 4 months on active study intervention, with breast surgery at week 16 and one month follow up period, after surgery. Patients will be randomly assigned to one of the following arms. 1. Anti-PD1 antibody pembrolizumab (Keytruda, Merck) will be infused day 12, at the standard dose of 200 mg IV over 30 minutes, repeated every 3 weeks until disease progression or unacceptable toxicity. 2. FLT3L (CDX-301, the recombinant human protein by Celldex) will be self-administered subcutaneously, in 5 consecutive daily injections, week 1, day 1-5.&#xD;
3. For all arms radiation therapy to the breast tumor will begin on week 2 (Day 8,10,12), at dose of 8 Gy x 3 fractions, every other day. 4. Letrozole (Femara ®, Novartis) 2.5 mg tabs, once a day, daily for 4 months, until surgery, and thereafter is decided by the treating physician</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Patients will be randomly assigned to one of the following arms. 1. Anti-PD1 antibody pembrolizumab (Keytruda, Merck) will be infused day 12, at the standard dose of 200 mg IV over 30 minutes, repeated every 3 weeks until disease progression or unacceptable toxicity. 2. FLT3L (CDX-301, the recombinant human protein by Celldex) will be self-administered subcutaneously, in 5 consecutive daily injections, week 1, day 1-5.&#xD;
3. For all arms radiation therapy to the breast tumor will begin on week 2 (Day 8,10,12), at dose of 8 Gy x 3 fractions, every other day. 4. Letrozole (Femara ®, Novartis) 2.5 mg tabs, once a day, daily for 4 months, until surgery, and thereafter is decided by the treating physician</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Tolerability will be demonstrated if no grade 3 or higher toxicities are observed in the first 8 patients, of each arm.</measure>
    <time_frame>3 years</time_frame>
    <description>Tolerability of adding immunotherapy to a combination of tumor radiotherapy and endocrine therapy in the neoadjuvant setting of newly diagnosed HR+ breast cancer patients will be assessed if no grade 3 or higher toxicities are observed in the first 8 patients of each arm. CTCAE version 5.0 will be used.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clinical response rate to tumor radiation +/-immunotherapy during standard endocrine therapy for HR+ breast cancer will be measured.</measure>
    <time_frame>3 years</time_frame>
    <description>Clinical response rate to tumor radiation +/-immunotherapy during standard endocrine therapy for HR+ breast cancer will be measured.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pathological response rate to tumor radiation +/-immunotherapy during standard endocrine therapy for HR+ breast cancer will be measured.</measure>
    <time_frame>3 years</time_frame>
    <description>Pathological response rate to tumor radiation +/-immunotherapy during standard endocrine therapy for HR+ breast cancer will be measured.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Local immune response will be measured by assessing tumor specimens for T-cell infiltration at baseline and and during treatment.</measure>
    <time_frame>4 years</time_frame>
    <description>Local immune response will be measured by assessing tumor specimens for T-cell infiltration at baseline and and during treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systemic immune response will be measured by collecting serial blood samples for serum and peripheral blood mononuclear cells (PBMCs) at multiple time points.</measure>
    <time_frame>4 years</time_frame>
    <description>Systemic immune response will be measured by collecting serial blood samples for serum and peripheral blood mononuclear cells (PBMCs) at multiple time points.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>ARM 1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Focal hypo-fractionated radiation therapy 8 Gy x 3 fractions, starting day 8, every other day (M/W/F or W/F/M or F/M/W).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ARM 2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Focal hypo-fractionated radiation therapy - 8 Gy x 3 fractions starting day 8, every other day (M/W/F or W/F/M or F/M/W). + Pembrolizumab, on day 12 (last day of radiotherapy), infused over 200mg IV over 30 minutes and then repeated every 3 weeks until disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ARM 3</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ftl-3 ligand, self-administered by subcutaneous injections at week 1, daily, for 5 consecutive days + Focal hypo-fractionated radiation therapy - 8 Gy x 3 fractions starting day 8, (every other day (M/W/F or W/F/M or F/M/W).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ARM 4</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ftl-3 ligand, self administered subcutaneous injections at day 1 for 5 consecutive days+ Focal hypo-fractionated Radiation therapy starting day 8, - 8 Gy x 3 fractions, every other day (M/W/F or W/F/M or F/M/W). + Pembrolizumab, on day 12 (last day of radiotherapy), 200mg IV infused over 30 minutes then repeated every 3 weeks until disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Focal Radiation therapy</intervention_name>
    <description>Focal hypo-fractionated radiation therapy 8 Gy x 3 fractions, starting day 8, every other day (M/W/F or W/F/M or F/M/W).</description>
    <arm_group_label>ARM 1</arm_group_label>
    <arm_group_label>ARM 2</arm_group_label>
    <arm_group_label>ARM 3</arm_group_label>
    <arm_group_label>ARM 4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab (200mg IV for 30 minutes</intervention_name>
    <description>Pembrolizumab, on day 12 (last day of radiotherapy), infused over 200mg IV over 30 minutes and then repeated every 3 weeks until disease progression or unacceptable toxicity.</description>
    <arm_group_label>ARM 2</arm_group_label>
    <arm_group_label>ARM 4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CDX-301</intervention_name>
    <description>Ftl-3 ligand, self-administered by subcutaneous injections at week 1, daily, for 5 consecutive days.</description>
    <arm_group_label>ARM 3</arm_group_label>
    <arm_group_label>ARM 4</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Post-menopausal female ≥ 18 years of age (Post-menopausal status defined as either 1)&#xD;
             at least 2 years without menstrual period or 2) or patients older than 50 with&#xD;
             serological evidence of post-menopausal status or 3) hysterectomized patients of any&#xD;
             age with FSH confirmation of post-menopausal status.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1&#xD;
&#xD;
          -  Biopsy proven diagnosis of ER+ PR+ or PR- HER2- breast cancer.&#xD;
&#xD;
          -  Clinical stage I(&gt;1.5cm, if N0) - III breast cancer, as per AJCC staging 8th edition.&#xD;
&#xD;
          -  Patient needs to be able to understand and demonstrate willingness to sign a written&#xD;
             informed consent document.&#xD;
&#xD;
        Adequate bone marrow reserve and liver function:&#xD;
&#xD;
        WBC ≥ 2000/uL Absolute neutrophil count (ANC) ≥1500/μL Platelets ≥100 000/μL Hemoglobin&#xD;
        ≥9.0 g/dL or ≥5.6 mmol/La Creatinine OR Measured or calculated creatinine clearance (GFR&#xD;
        can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant&#xD;
        with creatinine levels &gt;1.5 × institutional ULN Total bilirubin ≤1.5 ×ULN OR direct&#xD;
        bilirubin ≤ULN for participants with total bilirubin levels &gt;1.5 × ULN AST (SGOT) and ALT&#xD;
        (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases) International&#xD;
        normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time&#xD;
        (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or&#xD;
        aPTT is within therapeutic range of intended use of anticoagulants&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active connective tissue disorders, such as lupus or scleroderma requiring flare&#xD;
             therapy&#xD;
&#xD;
          -  Current use of systemic chemotherapy, endoctine therap or HER2-neu targeted therapy&#xD;
&#xD;
          -  Post surgical excision of breast cancer.&#xD;
&#xD;
          -  Previous radiotherapy of the same breast.&#xD;
&#xD;
          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with&#xD;
             an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4,&#xD;
             OX-40, CD137).&#xD;
&#xD;
          -  Inability to obtain histologic proof of breast cancer&#xD;
&#xD;
          -  Has received a live vaccine within 30 days prior to the first dose of study drug.&#xD;
&#xD;
        Examples of live vaccines include, but are not limited to, the following: measles, mumps,&#xD;
        rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin&#xD;
        (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed&#xD;
        virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are&#xD;
        live attenuated vaccines and are not allowed.&#xD;
&#xD;
          -  Is currently participating in or has participated in a study of an investigational&#xD;
             agent or has used an investigational device within 4 weeks prior to the first dose of&#xD;
             study treatment. Note: Participants who have entered the follow-up phase of an&#xD;
             investigational study may participate as long as it has been 4 weeks after the last&#xD;
             dose of the previous investigational agent.&#xD;
&#xD;
          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy&#xD;
             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of&#xD;
             immunosuppressive therapy within 7 days prior to the first dose of study drug.&#xD;
&#xD;
          -  Has a known additional malignancy (second primary) that is progressing or has required&#xD;
             active treatment within the past 3 years. Note: Participants with basal cell carcinoma&#xD;
             of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. cervical&#xD;
             cancer in situ) that have undergone potentially curative therapy are not excluded.&#xD;
&#xD;
          -  Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.&#xD;
&#xD;
          -  Has active autoimmune disease that has required systemic treatment in the past 2 years&#xD;
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive&#xD;
             drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid&#xD;
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a&#xD;
             form of systemic treatment.&#xD;
&#xD;
          -  Has a history of (non-infectious) pneumonitis that required steroids or has current&#xD;
             pneumonitis.&#xD;
&#xD;
          -  Has an active infection requiring systemic therapy.Has a known history of Human&#xD;
             Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by&#xD;
             local health authority.&#xD;
&#xD;
          -  Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]&#xD;
             reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is&#xD;
             detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required&#xD;
             unless mandated by local health authority.&#xD;
&#xD;
          -  Has a known history of active TB (Bacillus Tuberculosis). Note: optional based on&#xD;
             country.&#xD;
&#xD;
          -  Has known psychiatric or substance abuse disorders that would interfere with&#xD;
             cooperation with the requirements of the trial.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Newly diagnosed postmenopausal patients with clinical stage I-III ER+HER- invasive breast cancer will be eligible to participate in this trial. Patients with invasive ductal or lobular or mixed ductal/lobular breast cancers are eligible. (Clinical Stage 1 tumor size - &gt;1.5cm, if N0)</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Silvia Formenti, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Weill Cornell Medicine - New York Presbyterian Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sharanya Chandrasekhar, M.S.</last_name>
    <phone>646 962-2196</phone>
    <email>shc2043@med.cornell.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Pragya Yadav, Ph.D.</last_name>
    <phone>646-962-2199</phone>
    <email>pry2003@med.cornell.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Cedars-Sinai Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Icahn School of Medicine at Mt Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10027</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Denise Rodriguez</last_name>
      <phone>212-241-7840</phone>
      <email>denise.rodriguez3@mssm.edu</email>
    </contact>
    <investigator>
      <last_name>Nina Bharadwaj, M.D.,Ph.D</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>New York Presbyterian Hospital - Queens</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sarah Stankiewich</last_name>
      <phone>718-661-7246</phone>
      <email>sas9306@nyp.org</email>
    </contact>
    <contact_backup>
      <last_name>Sharanya Chandrasekhar</last_name>
      <phone>6469623110</phone>
      <email>shc2043@med.cornell.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Akkamma Ravi, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Weill Cornell Medicine New York Presbyterian Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Weill Cornell Medicine New York Presbyterian Hospital</last_name>
      <phone>646-962-2196</phone>
      <email>shc2043@med.cornell.edu</email>
    </contact>
    <investigator>
      <last_name>Silvia Formenti, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Brooklyn Methodist Hospital - NewYork Presbyterian</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>11215</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sharanya Chandrasekhar, M.S.</last_name>
      <phone>646-962-2196</phone>
      <email>shc2043@med.cornell.edu</email>
    </contact>
    <contact_backup>
      <last_name>Pragya Yadav, Ph.D.</last_name>
      <phone>6469622199</phone>
      <email>pry2003@med.cornell.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Hani Ashamalla, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Houston Methodist Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Genevieve Santibanez, CCRP</last_name>
      <phone>713-441-0685</phone>
      <email>gsantibanez@houstonmethodist.org</email>
    </contact>
    <investigator>
      <last_name>Jenny Chang, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>January 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 15, 2019</study_first_posted>
  <last_update_submitted>April 18, 2023</last_update_submitted>
  <last_update_submitted_qc>April 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 19, 2023</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>Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</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/NCT03804944
org study id: 1808019498
nct id: NCT03804944
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Newly diagnosed post-menopausal women with clinical stage II-III, HR+HER2- breast cancer are
      eligible to a randomized trial, concurrently open at five US academic institutions. Patients
      receiving 4 months of standard neoadjuvant hormonal therapy with letrozole are randomly
      assigned to one of 4 arms of a trial testing focal hypo-fractionated RT alone or with
      immunotherapy combinations.
Patients will be on the study for a total of 5 months, this includes 4 months on active study
      intervention, with breast surgery at week 16 and one month follow up period, after surgery.
      Patients will be randomly assigned to one of these 4 arms - 1. Anti-PD1 antibody
      pembrolizumab (Keytruda, Merck) will be infused day 12, at the standard dose of 200 mg IV
      over 30 minutes, repeated every 3 weeks until disease progression or unacceptable toxicity.
      2. FLT3L (CDX-301, the recombinant human protein by Celldex) will be self-administered
      subcutaneously, in 5 consecutive daily injections, week 1, day 1-5. 3. For all arms radiation
      therapy to the breast tumor will begin on week 2 (Day 8,10,12), at dose of 8 Gy x 3
      fractions, every other day. 4. Letrozole (Femara ®, Novartis) 2.5 mg tabs, once a day, daily
      for 4 months, until surgery, and thereafter is decided by the treating physician.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Patients will be on the study for a total of 5 months, this includes 4 months on active study intervention, with breast surgery at week 16 and one month follow up period, after surgery. Patients will be randomly assigned to one of the following arms. 1. Anti-PD1 antibody pembrolizumab (Keytruda, Merck) will be infused day 12, at the standard dose of 200 mg IV over 30 minutes, repeated every 3 weeks until disease progression or unacceptable toxicity. 2. FLT3L (CDX-301, the recombinant human protein by Celldex) will be self-administered subcutaneously, in 5 consecutive daily injections, week 1, day 1-5.
3. For all arms radiation therapy to the breast tumor will begin on week 2 (Day 8,10,12), at dose of 8 Gy x 3 fractions, every other day. 4. Letrozole (Femara ®, Novartis) 2.5 mg tabs, once a day, daily for 4 months, until surgery, and thereafter is decided by the treating physician
primary purpose: Treatment
masking: None (Open Label)
masking description: Patients will be randomly assigned to one of the following arms. 1. Anti-PD1 antibody pembrolizumab (Keytruda, Merck) will be infused day 12, at the standard dose of 200 mg IV over 30 minutes, repeated every 3 weeks until disease progression or unacceptable toxicity. 2. FLT3L (CDX-301, the recombinant human protein by Celldex) will be self-administered subcutaneously, in 5 consecutive daily injections, week 1, day 1-5.
3. For all arms radiation therapy to the breast tumor will begin on week 2 (Day 8,10,12), at dose of 8 Gy x 3 fractions, every other day. 4. Letrozole (Femara ®, Novartis) 2.5 mg tabs, once a day, daily for 4 months, until surgery, and thereafter is decided by the treating physician
measure: Tolerability will be demonstrated if no grade 3 or higher toxicities are observed in the first 8 patients, of each arm.
time frame: 3 years
description: Tolerability of adding immunotherapy to a combination of tumor radiotherapy and endocrine therapy in the neoadjuvant setting of newly diagnosed HR+ breast cancer patients will be assessed if no grade 3 or higher toxicities are observed in the first 8 patients of each arm. CTCAE version 5.0 will be used.
measure: Clinical response rate to tumor radiation +/-immunotherapy during standard endocrine therapy for HR+ breast cancer will be measured.
time frame: 3 years
description: Clinical response rate to tumor radiation +/-immunotherapy during standard endocrine therapy for HR+ breast cancer will be measured.
measure: Pathological response rate to tumor radiation +/-immunotherapy during standard endocrine therapy for HR+ breast cancer will be measured.
time frame: 3 years
description: Pathological response rate to tumor radiation +/-immunotherapy during standard endocrine therapy for HR+ breast cancer will be measured.
measure: Local immune response will be measured by assessing tumor specimens for T-cell infiltration at baseline and and during treatment.
time frame: 4 years
description: Local immune response will be measured by assessing tumor specimens for T-cell infiltration at baseline and and during treatment.
measure: Systemic immune response will be measured by collecting serial blood samples for serum and peripheral blood mononuclear cells (PBMCs) at multiple time points.
time frame: 4 years
description: Systemic immune response will be measured by collecting serial blood samples for serum and peripheral blood mononuclear cells (PBMCs) at multiple time points.
arm group label: ARM 1
arm group type: Active Comparator
description: Focal hypo-fractionated radiation therapy 8 Gy x 3 fractions, starting day 8, every other day (M/W/F or W/F/M or F/M/W).
arm group label: ARM 2
arm group type: Active Comparator
description: Focal hypo-fractionated radiation therapy - 8 Gy x 3 fractions starting day 8, every other day (M/W/F or W/F/M or F/M/W). + Pembrolizumab, on day 12 (last day of radiotherapy), infused over 200mg IV over 30 minutes and then repeated every 3 weeks until disease progression or unacceptable toxicity.
arm group label: ARM 3
arm group type: Active Comparator
description: Ftl-3 ligand, self-administered by subcutaneous injections at week 1, daily, for 5 consecutive days + Focal hypo-fractionated radiation therapy - 8 Gy x 3 fractions starting day 8, (every other day (M/W/F or W/F/M or F/M/W).
arm group label: ARM 4
arm group type: Active Comparator
description: Ftl-3 ligand, self administered subcutaneous injections at day 1 for 5 consecutive days+ Focal hypo-fractionated Radiation therapy starting day 8, - 8 Gy x 3 fractions, every other day (M/W/F or W/F/M or F/M/W). + Pembrolizumab, on day 12 (last day of radiotherapy), 200mg IV infused over 30 minutes then repeated every 3 weeks until disease progression or unacceptable toxicity.
intervention type: Radiation
intervention name: Focal Radiation therapy
description: Focal hypo-fractionated radiation therapy 8 Gy x 3 fractions, starting day 8, every other day (M/W/F or W/F/M or F/M/W).
arm group label: ARM 1
arm group label: ARM 2
arm group label: ARM 3
arm group label: ARM 4
intervention type: Drug
intervention name: Pembrolizumab (200mg IV for 30 minutes
description: Pembrolizumab, on day 12 (last day of radiotherapy), infused over 200mg IV over 30 minutes and then repeated every 3 weeks until disease progression or unacceptable toxicity.
arm group label: ARM 2
arm group label: ARM 4
intervention type: Biological
intervention name: CDX-301
description: Ftl-3 ligand, self-administered by subcutaneous injections at week 1, daily, for 5 consecutive days.
arm group label: ARM 3
arm group label: ARM 4
criteria: 
gender: Female
gender based: Yes
gender description: Newly diagnosed postmenopausal patients with clinical stage I-III ER+HER- invasive breast cancer will be eligible to participate in this trial. Patients with invasive ductal or lobular or mixed ductal/lobular breast cancers are eligible. (Clinical Stage 1 tumor size - >1.5cm, if N0)
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: Silvia Formenti, M.D.
role: Principal Investigator
affiliation: Weill Cornell Medicine - New York Presbyterian Hospital
last name: Sharanya Chandrasekhar, M.S.
phone: 646 962-2196
email: shc2043@med.cornell.edu
last name: Pragya Yadav, Ph.D.
phone: 646-962-2199
email: pry2003@med.cornell.edu
facility: 
status: Withdrawn
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Withdrawn
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Pembrolizumab
sharing ipd: No