<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/NCT02971748</url>
  </required_header>
  <id_info>
    <org_study_id>2016-0096</org_study_id>
    <secondary_id>NCI-2018-01297</secondary_id>
    <secondary_id>2016-0096</secondary_id>
    <nct_id>NCT02971748</nct_id>
  </id_info>
  <brief_title>Pembrolizumab in Treating Patients With Hormone Receptor Positive, Localized Inflammatory Breast Cancer Who Are Receiving Hormone Therapy and Did Not Achieve a Pathological Complete Response to Chemotherapy</brief_title>
  <official_title>A Phase II Study of Anti-PD-1 (Pembrolizumab) in Combination With Hormonal Therapy During or After Radiation in Patients With Hormone Receptor (HR)-Positive Localized Inflammatory Breast Cancer (IBC) Who Did Not Achieve a Pathological Complete Response (pCR) to Neoadjuvant Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</source>
  <oversight_info>
    <has_dmc>No</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>
      This phase II trial studies how well pembrolizumab works in treating patients with hormone&#xD;
      receptor positive inflammatory breast cancer that has not spread to other parts of the body,&#xD;
      who are receiving hormone therapy and did not achieve a pathological complete response to&#xD;
      chemotherapy. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the&#xD;
      body's immune system attack the cancer, and may interfere with the ability of tumor cells to&#xD;
      grow and spread.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the disease free survival (DFS) at 2 years of patients with maintenance&#xD;
      therapy using pembrolizumab in combination with standard adjuvant hormonal therapy.&#xD;
&#xD;
      II. To determine the safety and toxicity profile of primary inflammatory breast cancer (IBC)&#xD;
      patients who received combination of pembrolizumab and hormone receptor blockade.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. To investigate the association between immune related biomarkers in the peripheral blood&#xD;
      and tumor tissue, such as PD-L1 expression, with safety and efficacy for IBC patients treated&#xD;
      with pembrolizumab.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat&#xD;
      every 21 days for up to 24 months in the absence of disease progression or unacceptable&#xD;
      toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 1 and 24 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 26, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Disease free survival (DFS)</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>Will be summarized with a corresponding 95% confidence interval. DFS will be compared with the historical control rate of 60% at year two by using a one-sided exponential MLE test. Cox proportional hazards regression analysis will be used to model the association between DFS and disease and demographic covariates of interest, including immune-related biomarkers in the peripheral blood and tumor tissue.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>From the start of the study up to 24 months</time_frame>
    <description>Will be summarized with a corresponding 95% confidence interval. OS will be compared with the historical control rate of 60% at year two by using a one-sided exponential MLE test. Cox proportional hazards regression analysis will be used to model the association between OS and disease and demographic covariates of interest, including immune-related biomarkers in the peripheral blood and tumor tissue.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>Up to 1 month after last pembrolizumab dose</time_frame>
    <description>Adverse events will be summarized by grade and category.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">37</enrollment>
  <condition>Anatomic Stage IIIB Breast Cancer AJCC v8</condition>
  <condition>Anatomic Stage IIIC Breast Cancer AJCC v8</condition>
  <condition>Breast Inflammatory Carcinoma</condition>
  <condition>Prognostic Stage IIIB Breast Cancer AJCC v8</condition>
  <condition>Prognostic Stage IIIC Breast Cancer AJCC v8</condition>
  <arm_group>
    <arm_group_label>Treatment (pembrolizumab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (pembrolizumab)</arm_group_label>
    <other_name>Keytruda</other_name>
    <other_name>Lambrolizumab</other_name>
    <other_name>MK-3475</other_name>
    <other_name>SCH 900475</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Is willing and able to provide written informed consent for the trial.&#xD;
&#xD;
          -  Has histological confirmation of breast carcinoma.&#xD;
&#xD;
          -  Has confirmed inflammatory breast cancer by using international consensus criteria:&#xD;
&#xD;
               -  Onset: Rapid onset of breast erythema, edema and/or peau d'orange, and/or warm&#xD;
                  breast, with/without an underlying breast mass.&#xD;
&#xD;
               -  Duration: History of such findings no more than 6 months.&#xD;
&#xD;
               -  Extent: Erythema occupying at least 1/3 of whole breast.&#xD;
&#xD;
               -  Pathology: Pathologic confirmation of invasive carcinoma.&#xD;
&#xD;
          -  Did not achieve pathological complete response (pCR) to any chemotherapy that was&#xD;
             given with the intention to induce best response prior surgery. pCR is defined as the&#xD;
             current American Joint Committee on Cancer (AJCC) breast cancer staging.&#xD;
&#xD;
          -  Is HER2 normal, defined as HER2 0 or 1+ by immunohistochemistry (IHC) and negative by&#xD;
             fluorescence in situ hybridization (FISH) if performed; or HER2 is 2+ by IHC and&#xD;
             negative by FISH; or HER2 negative by FISH if IHC is not performed.&#xD;
&#xD;
          -  Has positive estrogen receptor (ER) or progesterone receptor (PR) status. ER or PR &gt;=&#xD;
             10%.&#xD;
&#xD;
          -  Has a performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG)&#xD;
             performance scale.&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1,500/mcL.&#xD;
&#xD;
          -  Platelets &gt;= 100,000 /mcL.&#xD;
&#xD;
          -  Hemoglobin (Hgb) &gt;= 9 g/dL.&#xD;
&#xD;
          -  Creatinine levels &lt; 1.5 x upper limit of normal (ULN).&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x ULN.&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =&lt; 2.5 x ULN.&#xD;
&#xD;
          -  Subjects of reproductive potential must agree to avoid becoming pregnant or&#xD;
             impregnating a partner, respectively, while receiving study drug and for 120 days&#xD;
             after the last dose of study drug by complying with one of the following: (1) practice&#xD;
             abstinence from heterosexual activity; OR (2) use (or have their partner use)&#xD;
             acceptable contraception during heterosexual activity. Acceptable methods of&#xD;
             contraception are: Single method (one of the following is acceptable): (1)&#xD;
             intrauterine device (IUD); (2) vasectomy of a female subject's male partner; (3)&#xD;
             contraceptive rod implanted into the skin. Combination method (requires use of two of&#xD;
             the following): (1) diaphragm with spermicide (cannot be used in conjunction with&#xD;
             cervical cap/spermicide); (2) cervical cap with spermicide (nulliparous women only);&#xD;
             (3) contraceptive sponge (nulliparous women only); (4) male condom or female condom&#xD;
             (cannot be used together); (5) hormonal contraceptive: oral contraceptive pill&#xD;
             (estrogen/progestin pill or progestin-only pill), contraceptive skin patch, vaginal&#xD;
             contraceptive ring, or subcutaneous contraceptive injection&#xD;
&#xD;
          -  Female subjects will be considered of non-reproductive potential if they are either:&#xD;
&#xD;
               -  Postmenopausal (defined as at least 12 months with no menses without an&#xD;
                  alternative medical cause; in women &lt; 45 years of age a high follicle stimulating&#xD;
                  hormone (FSH) level in the postmenopausal range may be used to confirm a&#xD;
                  post-menopausal state in women not using hormonal contraception or hormonal&#xD;
                  replacement therapy. In the absence of 12 months of amenorrhea, a single FSH&#xD;
                  measurement is insufficient.); OR&#xD;
&#xD;
               -  Have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or&#xD;
                  bilateral tubal ligation/occlusion, at least 6 weeks prior to screening; OR&#xD;
&#xD;
               -  Has a congenital or acquired condition that prevents childbearing.&#xD;
&#xD;
          -  Male subjects will be considered to be of non-reproductive potential if they have&#xD;
             azoospermia (whether due to having had a vasectomy or due to an underlying medical&#xD;
             condition)&#xD;
&#xD;
          -  Has negative serum or urine pregnancy test for subjects of childbearing potential&#xD;
             within 10 days before first dose.&#xD;
&#xD;
          -  Have completed radiation (if candidate for post-mastectomy radiation) or plans to&#xD;
             begin radiation and endocrine therapy within 28 days.&#xD;
&#xD;
          -  If patient has already started hormonal blockade therapy after radiation as adjuvant&#xD;
             therapy, the patient is eligible as long as the hormonal therapy was initiated no more&#xD;
             than 6 months by the time of screening and can start the study drug within 4 weeks&#xD;
             since the completion of screening.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Is currently participating in a study of an investigational anti-cancer agent.&#xD;
&#xD;
          -  Has a diagnosis of immunodeficiency or any other form of immunosuppressive therapy.&#xD;
&#xD;
          -  Has not recovered from adverse events due to prior therapies, i.e. monoclonal&#xD;
             antibody, chemotherapy, targeted small molecule therapy, radiation therapy, or&#xD;
             surgery.&#xD;
&#xD;
               -  Note: Subjects with grade 2 neuropathy, alopecia and general disorders and&#xD;
                  administration site conditions (per Common Terminology Criteria for Adverse&#xD;
                  Events [CTCAE] version 4.0) are an exception to this criterion and may qualify&#xD;
                  for the study.&#xD;
&#xD;
          -  Has a known history of prior malignancy with the exception of basal cell carcinoma of&#xD;
             the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or in situ&#xD;
             cervical cancer, and has undergone potentially curative therapy and has no evidence of&#xD;
             recurrence over the last 1 year since completion of curative therapy.&#xD;
&#xD;
          -  Has an active autoimmune disease requiring systemic treatment within the past 3 months&#xD;
             or a documented history of clinically severe autoimmune disease, or immunosuppressive&#xD;
             agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an&#xD;
             exception to this rule. Subjects that require intermittent use of bronchodilators,&#xD;
             inhaled steroid or local steroid injections to the skin would not be excluded from the&#xD;
             study. Subjects with hypothyroidism stable on hormone replacement or Sjogren's&#xD;
             syndrome will not be excluded from the study.&#xD;
&#xD;
          -  Has a history of (non-infectious) pneumonitis that required steroids or current&#xD;
             pneumonitis.&#xD;
&#xD;
          -  Has an active infection requiring systemic therapy.&#xD;
&#xD;
          -  Has known psychiatric or substance abuse disorders that would interfere with&#xD;
             cooperation with the requirements of the trial.&#xD;
&#xD;
          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or&#xD;
             anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including&#xD;
             ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation&#xD;
             or checkpoint pathways).&#xD;
&#xD;
          -  Has a known history of human immunodeficiency virus (HIV).&#xD;
&#xD;
          -  Has a known active hepatitis B or hepatitis C.&#xD;
&#xD;
          -  Have received a live vaccine within 30 days prior to the first dose of trial&#xD;
             treatment.&#xD;
&#xD;
          -  Gastrointestinal tract disease or defect or previous history of colitis.&#xD;
&#xD;
          -  Has proven or suspected distant metastasis that involves occurrence of breast cancer&#xD;
             outside of locoregional breast and lymph nodes area.&#xD;
&#xD;
          -  Subjects requiring daily corticosteroids either via oral route of administration (po)&#xD;
             or infusion.&#xD;
&#xD;
          -  Myocardial infarction within 6 months before starting therapy, symptomatic congestive&#xD;
             heart failure (New York Heart Association &gt; class II), unstable angina, or unstable&#xD;
             cardiac arrhythmia requiring medication.&#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>Clinton Yam</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>MD Anderson Cancer Center</description>
  </link>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>November 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 23, 2016</study_first_posted>
  <last_update_submitted>August 17, 2023</last_update_submitted>
  <last_update_submitted_qc>August 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 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>
    <mesh_term>Inflammatory 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>
  <!-- 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/NCT02971748
org study id: 2016-0096
secondary id: NCI-2018-01297
secondary id: 2016-0096
nct id: NCT02971748
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well pembrolizumab works in treating patients with hormone
      receptor positive inflammatory breast cancer that has not spread to other parts of the body,
      who are receiving hormone therapy and did not achieve a pathological complete response to
      chemotherapy. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the
      body's immune system attack the cancer, and may interfere with the ability of tumor cells to
      grow and spread.
PRIMARY OBJECTIVES:

      I. To determine the disease free survival (DFS) at 2 years of patients with maintenance
      therapy using pembrolizumab in combination with standard adjuvant hormonal therapy.

      II. To determine the safety and toxicity profile of primary inflammatory breast cancer (IBC)
      patients who received combination of pembrolizumab and hormone receptor blockade.

      EXPLORATORY OBJECTIVES:

      I. To investigate the association between immune related biomarkers in the peripheral blood
      and tumor tissue, such as PD-L1 expression, with safety and efficacy for IBC patients treated
      with pembrolizumab.

      OUTLINE:

      Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat
      every 21 days for up to 24 months in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up at 1 and 24 months.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Disease free survival (DFS)
time frame: Up to 24 months
description: Will be summarized with a corresponding 95% confidence interval. DFS will be compared with the historical control rate of 60% at year two by using a one-sided exponential MLE test. Cox proportional hazards regression analysis will be used to model the association between DFS and disease and demographic covariates of interest, including immune-related biomarkers in the peripheral blood and tumor tissue.
measure: Overall survival (OS)
time frame: From the start of the study up to 24 months
description: Will be summarized with a corresponding 95% confidence interval. OS will be compared with the historical control rate of 60% at year two by using a one-sided exponential MLE test. Cox proportional hazards regression analysis will be used to model the association between OS and disease and demographic covariates of interest, including immune-related biomarkers in the peripheral blood and tumor tissue.
measure: Incidence of adverse events
time frame: Up to 1 month after last pembrolizumab dose
description: Adverse events will be summarized by grade and category.
arm group label: Treatment (pembrolizumab)
arm group type: Experimental
description: Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
intervention type: Biological
intervention name: Pembrolizumab
description: Given IV
arm group label: Treatment (pembrolizumab)
other name: Keytruda
other name: Lambrolizumab
other name: MK-3475
other name: SCH 900475
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinton Yam
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
facility: 
country: United States
url: http://www.mdanderson.org
description: MD Anderson Cancer Center
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Inflammatory Breast Neoplasms
mesh term: Pembrolizumab