<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/NCT04418219</url>
  </required_header>
  <id_info>
    <org_study_id>20P.020</org_study_id>
    <nct_id>NCT04418219</nct_id>
  </id_info>
  <brief_title>Breast Cancer Vaccine in Combination With Pembrolizumab for Treatment of Persistent, Recurrent, or Metastatic Breast Cancer</brief_title>
  <official_title>A Phase I/II Study of the SV-BR-1-GM Regimen in HLA Matched Metastatic Breast Cancer Patients in Combination With Pembrolizumab</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Thomas Jefferson University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Thomas Jefferson 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>
      This phase I/II trial studies the side effects of a breast cancer vaccine (SV-BR-1-GM) and&#xD;
      how well it works in combination with pembrolizumab for the treatment of breast cancer that&#xD;
      is persistent, has come back (recurrent), or has spread to other places in the body&#xD;
      (metastatic). Breast cancer vaccine SV-BR-1-GM is a human breast cancer cell line that has&#xD;
      been genetically engineered to produce a substance called &quot;GM-CSF&quot; (granulocyte-macrophage&#xD;
      colony stimulating factor) which occurs naturally in the body. GM-CSF is normally produced by&#xD;
      white blood cells and helps the body develop immunity to disease-causing germs. Immunotherapy&#xD;
      with monoclonal antibodies such as pembrolizumab may help the body's immune system attack the&#xD;
      cancer and may interfere with the ability of tumor cells to grow and spread. Anti-cancer&#xD;
      drugs such as cyclophosphamide may help boost the immune response. Interferon alpha 2b may&#xD;
      help stimulate the immune system to fight cancer. This trial may help doctors see whether&#xD;
      SV-BR-1-GM injections help boost the immune system and/or help control or help shrink breast&#xD;
      cancer along with the other drugs that also boost the immune system.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the safety of the allogeneic GM-CSF-secreting breast cancer vaccine SV-BR-1-GM&#xD;
      (SV-BR-1-GM) regimen when administered in combination with pembrolizumab in patients with&#xD;
      human leukocyte antigen (HLA) match. (Phase I) II. To evaluate the overall response rate of&#xD;
      the SV-BR1-GM regimen in combination with pembrolizumab. (Phase II)&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the non-progressive rate of the SV-BR-1-GM regimen in combination with&#xD;
      pembrolizumab.&#xD;
&#xD;
      II. To evaluate the duration of response of the SV-BR-1-GM regimen in combination with&#xD;
      pembrolizumab.&#xD;
&#xD;
      III. To evaluate immune responses elicited by the SV-BR-1-GM regimen when administered in&#xD;
      combination with pembrolizumab.&#xD;
&#xD;
      IV. To evaluate patient and tumor characteristics that may be predictive of responses to the&#xD;
      SV-BR-1-GM regimen when administered in combination with pembrolizumab.&#xD;
&#xD;
      V. To evaluate quality of life (QOL) in patients administered the SV-BR-1-GM regimen in&#xD;
      combination with pembrolizumab by the Edmonton Symptom Assessment Survey.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive cyclophosphamide intravenously (IV) over 1-2 hours on day 1, SV-BR-1-GM&#xD;
      intradermally (ID) on day 3, pembrolizumab IV over 30 minutes on day 5, and&#xD;
      interferon-alpha-2b ID on days 5 and 7. Cycles repeat every 21 days for up to 2 years in the&#xD;
      absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 2-4 weeks and then every 3&#xD;
      months for 1 year.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Funding Discontinued&#xD;
  </why_stopped>
  <start_date type="Anticipated">December 21, 2020</start_date>
  <completion_date type="Anticipated">January 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">January 1, 2023</primary_completion_date>
  <phase>Phase 1/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>Incidence of adverse events</measure>
    <time_frame>up to 1 year</time_frame>
    <description>Toxicity will be determined using the Common Terminology Criteria for Adverse Events (CTCAE v 5.0).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>up to 1 year</time_frame>
    <description>Will be defined as complete response (CR), partial response (PR) or stable disease (SD) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune-modified (i)RECIST. The method of Atkinson and Brown will be used to allow for the two-stage design.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Non-progressive rate</measure>
    <time_frame>Up to one year</time_frame>
    <description>Defined as time to progression of disease, measured by CR, PR or SD per RECIST 1.1 and iRECIST. This will be estimated using the Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Durability of response</measure>
    <time_frame>Up to one year</time_frame>
    <description>Defined in time as time to progressive disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Delayed type hypersensitivity (DTH) skin tests</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Will be evaluated comparing pre-dose with post-dose samples using simple statistical testing (e.g. Student's t-Test).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T cell responses to SV-BR-1</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Will be evaluated comparing pre-dose with post-dose samples using simple statistical testing (e.g. Student's t-Test).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor expression of PD-L1</measure>
    <time_frame>Up to 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor expression of PD-L2</measure>
    <time_frame>Up to 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor expression of cancer/testis antigens such as PRAME</measure>
    <time_frame>Up to 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Type of breast cancer (estrogen receptor [ER] positive, HER2 positive, triple negative)</measure>
    <time_frame>Up to 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Edmonton Symptom Assessment Survey</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Assessment of nine symptoms commonly seen in cancer patients. Patients rate on scale of 0-10 with 0 meaning the symptom is absent and 10 meaning the worst possible severity.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Anatomic Stage IV Breast Cancer AJCC v8</condition>
  <condition>Metastatic Breast Carcinoma</condition>
  <condition>Prognostic Stage IV Breast Cancer AJCC v8</condition>
  <condition>Recurrent Breast Carcinoma</condition>
  <condition>Refractory Breast Carcinoma</condition>
  <arm_group>
    <arm_group_label>Treatment (SV-BR-1GM, pembrolizumab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive cyclophosphamide IV over 1-2 hours on day 1, SV-BR-1-GM ID on day 3, pembrolizumab IV over 30 minutes on day 5, and interferon-alpha-2b ID on days 5 and 7. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>alkylating agent used in the treatment of several forms of cancer including leukemias, lymphomas and breast cancer.</description>
    <arm_group_label>Treatment (SV-BR-1GM, pembrolizumab)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Allogeneic GM-CSF-secreting Breast Cancer Vaccine SV-BR-1-GM</intervention_name>
    <description>Breast Cancer Vaccine SV-BR-1-GM, Bria-IMT, GM-CSF Gene-transfected Breast Cancer Vaccine SV-BR-1-GM, SV-BR-1 Breast Cancer Cell Line Vaccine, SV-BR-1-GM, SV-BR-1-GM Vaccine</description>
    <arm_group_label>Treatment (SV-BR-1GM, pembrolizumab)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>1374853-91-4, Immunoglobulin G4, Anti-(Human Programmed Cell Death 1); Humanized Mouse Monoclonal (228-L-proline(H10-S&gt;P))gamma 4 Heavy Chain (134-218'')-disulfide with Humanized Mouse Monoclonal Kappa Light Chain Dimer (226-226'''':229-229'''')-bisdisulfide, Keytruda, Lambrolizumab, MK-3475, PEMBROLIZUMAB, SCH 900475</description>
    <arm_group_label>Treatment (SV-BR-1GM, pembrolizumab)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Recombinant Interferon Alpha 2b-like Protein</intervention_name>
    <description>Novaferon, Recombinant IFN Alfa-2b-like Protein</description>
    <arm_group_label>Treatment (SV-BR-1GM, pembrolizumab)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionnaire Administration</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Treatment (SV-BR-1GM, pembrolizumab)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Quality of Life Assessment</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Treatment (SV-BR-1GM, pembrolizumab)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have evidence of persistent, recurrent, or progressive metastatic breast cancer for&#xD;
             which there is no known or established treatment available with curative intent, after&#xD;
             failing at least two courses of community standard systemic treatment with&#xD;
             chemotherapy (and endocrine therapy, if appropriate)&#xD;
&#xD;
               -  Human epidermal growth factor 2 (HER2) positive and estrogen receptor (ER) or&#xD;
                  progesterone receptor (PR) positive tumors: must be refractory to hormonal&#xD;
                  therapy (e.g., aromatase inhibitor, tamoxifen or fulvestrant) and previously&#xD;
                  treated with at least 1 regimen that includes at least two antiHER2 agents (e.g.,&#xD;
                  trastuzumab and pertuzumab)&#xD;
&#xD;
               -  ER/PR positive, HER2 negative tumors: must be refractory to hormonal therapy&#xD;
                  (e.g. aromatase inhibitor, tamoxifen or fulvestrant) and previously treated with&#xD;
                  at least 2 chemotherapy containing regimens&#xD;
&#xD;
               -  HER2 positive and ER/PR negative tumors: must have failed at least 2 regimens&#xD;
                  including at least two anti-HER2 agents (e.g., trastuzumab and pertuzumab)&#xD;
&#xD;
               -  Triple negative tumors (defined as ER &lt; 1%, PR &lt; 1% as per American Society of&#xD;
                  Clinical Oncology College of American Pathologists [ASCO CAP] guidelines,&#xD;
                  HER2/neu 0-1 by immunohistochemistry [IHC] or negative by dual in situ&#xD;
                  hybridization [ISH]): Must have failed two other treatment lines including either&#xD;
                  a taxane and/or atezolizumab. Patients can have had atezolizumab (PD-L1&#xD;
                  inhibitor) or PD-1 therapy previously&#xD;
&#xD;
          -  Patients will only be eligible for this study if they have at least one human&#xD;
             leukocyte antigen (HLA) match:&#xD;
&#xD;
               -  HLA-A*24:02&#xD;
&#xD;
               -  HLA-B*35:08&#xD;
&#xD;
               -  HLA-B*55:01&#xD;
&#xD;
               -  HLA-C*04:01&#xD;
&#xD;
               -  HLA-C*01:02&#xD;
&#xD;
               -  HLA-DRB3*01:01&#xD;
&#xD;
               -  HLA-DRB3*02:02&#xD;
&#xD;
          -  Have expected survival of at least 4 months&#xD;
&#xD;
          -  Have adequate performance status (Eastern Cooperative Oncology Group [ECOG] 0-1)&#xD;
&#xD;
          -  A female participant is eligible to participate if she is not pregnant, not&#xD;
             breastfeeding, and at least one of the following conditions applies:&#xD;
&#xD;
               -  Not a woman of childbearing potential (WOCBP) defined as spontaneous cessation of&#xD;
                  menstrual cycle for at least 12 months or surgical history of hysterectomy or&#xD;
                  bilateral salpingoopherectomy OR&#xD;
&#xD;
               -  A WOCBP who agrees to take appropriate precautions to avoid becoming pregnant&#xD;
                  during the treatment period and for at least 90 days plus 30 days (a menstruation&#xD;
                  cycle) for study treatments with risk of genotoxicity after the last dose of&#xD;
                  study treatment&#xD;
&#xD;
          -  The participant (or legally acceptable representative if applicable) provides written&#xD;
             informed consent for the trial&#xD;
&#xD;
          -  Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST)&#xD;
             1.1. Lesions situated in a previously irradiated area are considered measurable if&#xD;
             progression has been demonstrated in such lesions&#xD;
&#xD;
          -  If any brain metastases, must have had prior radiation therapy for brain metastases&#xD;
&#xD;
          -  Systemic glucocorticoids for any purpose other than to modulate symptoms from an event&#xD;
             of clinical interest of suspected immunologic etiology are allowed. The use of&#xD;
             physiologic doses of corticosteroids may be approved after consultation with the&#xD;
             principal investigator&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1500/uL (collected within 14 days prior to the&#xD;
             start of study treatment)&#xD;
&#xD;
          -  Platelets &gt;= 100,000/uL (collected within 14 days prior to the start of study&#xD;
             treatment)&#xD;
&#xD;
          -  Hemoglobin &gt;= 9.0 g/dL or &gt;= 5.6 mmol/L (collected within 14 days prior to the start&#xD;
             of study treatment)&#xD;
&#xD;
             * Criteria must be met without erythropoietin dependency and without packed red blood&#xD;
             cell (pRBC) transfusion within last 2 weeks&#xD;
&#xD;
          -  Creatinine =&lt; 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine&#xD;
             clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or&#xD;
             creatinine clearance [CrCl]) &gt;= 30 mL/min for participant with creatinine levels &gt; 1.5&#xD;
             x institutional ULN (collected within 14 days prior to the start of study treatment)&#xD;
&#xD;
             * Creatinine clearance (CrCl) should be calculated per institutional standard&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x ULN OR direct bilirubin =&lt; ULN for participants with total&#xD;
             bilirubin levels &gt; 1.5 ULN&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase) [[SGOT])&#xD;
             and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase) [[SGPT]) =&lt;&#xD;
             2.5 x ULN (=&lt; 5 x ULN for participants with liver metastases) (collected within 14&#xD;
             days prior to the start of study treatment)&#xD;
&#xD;
          -  International normalized ratio (INR) OR prothrombin time (PT) =&lt; 1.5 x ULN unless&#xD;
             participant is receiving anticoagulant therapy as long as PT or activated partial&#xD;
             thromboplastin time (aPTT) is within therapeutic range of intended use of&#xD;
             anticoagulants (collected within 14 days prior to the start of study treatment)&#xD;
&#xD;
          -  Activated partial thromboplastin time (aPTT) =&lt; 1.5 x ULN unless participant is&#xD;
             receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of&#xD;
             intended use of anticoagulants (collected within 14 days prior to the start of study&#xD;
             treatment)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Concurrent or recent chemotherapy, radiotherapy, immunotherapy, or general&#xD;
             anesthesia/major surgery within 4 weeks&#xD;
&#xD;
          -  Patients must have recovered from all known or expected toxicities from previous&#xD;
             treatment and passed a treatment-free &quot;washout&quot; period of 3 weeks before starting this&#xD;
             program&#xD;
&#xD;
          -  If participant received major surgery, they must have recovered adequately from the&#xD;
             toxicity and/or complications from the intervention prior to starting study treatment&#xD;
&#xD;
          -  Has received prior systemic anti-cancer therapy including investigational agents&#xD;
             within 4 weeks prior to enrollment&#xD;
&#xD;
          -  Participants must have recovered from all adverse events (AEs) due to previous&#xD;
             therapies to =&lt; grade 1 or baseline&#xD;
&#xD;
             * Participants with =&lt; grade 2 neuropathy and/or alopecia may be eligible&#xD;
&#xD;
          -  Has received a live vaccine within 30 days prior to the first dose of study drug.&#xD;
             Examples of live vaccines include, but are not limited to, the following: measles,&#xD;
             mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus&#xD;
             Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection&#xD;
             are generally killed virus vaccines and are allowed; however, intranasal influenza&#xD;
             vaccines (e.g, FluMist) are live attenuated vaccines and are not allowed&#xD;
&#xD;
          -  Has known active central nervous system (CNS) metastases and/or carcinomatous&#xD;
             meningitis. Participants with previously treated brain metastases may participate&#xD;
             provided they are radiologically stable, i.e. without evidence of progression for at&#xD;
             least 4 weeks by repeat imaging (note that the repeat imaging should be performed&#xD;
             during study screening), clinically stable and without requirement of steroid&#xD;
             treatment for at least 14 days prior to first dose of study treatment&#xD;
&#xD;
          -  History of clinical hypersensitivity to granulocyte-macrophage colony-stimulating&#xD;
             factor (GM-CSF), interferon-alpha-2b, yeast, beef, or to any components used in the&#xD;
             preparation of SV-BR-1-GM&#xD;
&#xD;
          -  Has severe hypersensitivity (&gt;= grade 3) to pembrolizumab and/or any of its excipients&#xD;
&#xD;
          -  Proteinuria &gt;1+ on urinalysis or &gt;1 gm/24hr&#xD;
&#xD;
          -  Left ventricular ejection fraction (LVEF as determined by cardiac echo or multigated&#xD;
             acquisition scan [MUGA] scan) below the normal limits of the institutions' specific&#xD;
             testing range. This assessment may be repeated once at the discretion of the&#xD;
             Investigator with the approval of the principal investigator&#xD;
&#xD;
          -  New York Heart Association stage 3 or 4 cardiac disease&#xD;
&#xD;
          -  A pleural or pericardial effusion of moderate severity or worse&#xD;
&#xD;
          -  WOCBP who have a positive urine pregnancy test within 7 days prior to enrollment&#xD;
&#xD;
             * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy&#xD;
             test will be required&#xD;
&#xD;
          -  Women who are pregnant or nursing&#xD;
&#xD;
          -  Patients with concurrent second malignancy. Persons with previous malignancies&#xD;
             effectively treated and not requiring treatment for &gt; 24 months are eligible, provided&#xD;
             there is unambiguous documentation that current local recurrence or metastatic site&#xD;
             represents recurrence of the primary breast malignancy&#xD;
&#xD;
          -  Patients who are human immunodeficiency virus (HIV) positive (by self-report) or have&#xD;
             clinical or laboratory features indicative of acquired immunodeficiency syndrome&#xD;
             (AIDS)&#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 ribonucleic acid [RNA] is&#xD;
             detected) infection&#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&#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 (e.g. 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;
          -  Patients who require systemic steroids at doses &gt; 10 mg daily of prednisone or&#xD;
             equivalent or any immunosuppressive drugs. Beta-blocker therapy, while not&#xD;
             exclusionary, is discouraged and alternatives should be sought if possible. The&#xD;
             beta-blocker might compromise use of epinephrine for the rare possibility of&#xD;
             anaphylaxis&#xD;
&#xD;
          -  Patients with a history of colitis&#xD;
&#xD;
          -  Patients with severe psychiatric (e.g., schizophrenia, bipolar, or borderline&#xD;
             personality disorder) or other clinically progressive major medical problems, unless&#xD;
             approved by the principal investigator&#xD;
&#xD;
          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality&#xD;
             that might confound the results of the study, interfere with the subject's&#xD;
             participation for the full duration of the study, or is not in the best interest of&#xD;
             the subject to participate, in the opinion of the treating investigator&#xD;
&#xD;
          -  Patients may not be on a concurrent treatment clinical trial, unless approved by&#xD;
             principal investigator&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Sidney Kimmel Cancer Center at Thomas Jefferson University</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>March 16, 2020</study_first_submitted>
  <study_first_submitted_qc>June 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 5, 2020</study_first_posted>
  <last_update_submitted>June 3, 2021</last_update_submitted>
  <last_update_submitted_qc>June 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 7, 2021</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>Carcinoma</mesh_term>
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Interferons</mesh_term>
    <mesh_term>Interferon-alpha</mesh_term>
    <mesh_term>Interferon alpha-2</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <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/NCT04418219
org study id: 20P.020
nct id: NCT04418219
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase I/II trial studies the side effects of a breast cancer vaccine (SV-BR-1-GM) and
      how well it works in combination with pembrolizumab for the treatment of breast cancer that
      is persistent, has come back (recurrent), or has spread to other places in the body
      (metastatic). Breast cancer vaccine SV-BR-1-GM is a human breast cancer cell line that has
      been genetically engineered to produce a substance called "GM-CSF" (granulocyte-macrophage
      colony stimulating factor) which occurs naturally in the body. GM-CSF is normally produced by
      white blood cells and helps the body develop immunity to disease-causing germs. 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. Anti-cancer
      drugs such as cyclophosphamide may help boost the immune response. Interferon alpha 2b may
      help stimulate the immune system to fight cancer. This trial may help doctors see whether
      SV-BR-1-GM injections help boost the immune system and/or help control or help shrink breast
      cancer along with the other drugs that also boost the immune system.
PRIMARY OBJECTIVES:

      I. To evaluate the safety of the allogeneic GM-CSF-secreting breast cancer vaccine SV-BR-1-GM
      (SV-BR-1-GM) regimen when administered in combination with pembrolizumab in patients with
      human leukocyte antigen (HLA) match. (Phase I) II. To evaluate the overall response rate of
      the SV-BR1-GM regimen in combination with pembrolizumab. (Phase II)

      SECONDARY OBJECTIVES:

      I. To evaluate the non-progressive rate of the SV-BR-1-GM regimen in combination with
      pembrolizumab.

      II. To evaluate the duration of response of the SV-BR-1-GM regimen in combination with
      pembrolizumab.

      III. To evaluate immune responses elicited by the SV-BR-1-GM regimen when administered in
      combination with pembrolizumab.

      IV. To evaluate patient and tumor characteristics that may be predictive of responses to the
      SV-BR-1-GM regimen when administered in combination with pembrolizumab.

      V. To evaluate quality of life (QOL) in patients administered the SV-BR-1-GM regimen in
      combination with pembrolizumab by the Edmonton Symptom Assessment Survey.

      OUTLINE:

      Patients receive cyclophosphamide intravenously (IV) over 1-2 hours on day 1, SV-BR-1-GM
      intradermally (ID) on day 3, pembrolizumab IV over 30 minutes on day 5, and
      interferon-alpha-2b ID on days 5 and 7. Cycles repeat every 21 days for up to 2 years in the
      absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 2-4 weeks and then every 3
      months for 1 year.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of adverse events
time frame: up to 1 year
description: Toxicity will be determined using the Common Terminology Criteria for Adverse Events (CTCAE v 5.0).
measure: Objective response rate (ORR)
time frame: up to 1 year
description: Will be defined as complete response (CR), partial response (PR) or stable disease (SD) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune-modified (i)RECIST. The method of Atkinson and Brown will be used to allow for the two-stage design.
measure: Non-progressive rate
time frame: Up to one year
description: Defined as time to progression of disease, measured by CR, PR or SD per RECIST 1.1 and iRECIST. This will be estimated using the Kaplan-Meier method.
measure: Durability of response
time frame: Up to one year
description: Defined in time as time to progressive disease.
measure: Delayed type hypersensitivity (DTH) skin tests
time frame: Up to 1 year
description: Will be evaluated comparing pre-dose with post-dose samples using simple statistical testing (e.g. Student's t-Test).
measure: T cell responses to SV-BR-1
time frame: Up to 1 year
description: Will be evaluated comparing pre-dose with post-dose samples using simple statistical testing (e.g. Student's t-Test).
measure: Tumor expression of PD-L1
time frame: Up to 1 year
measure: Tumor expression of PD-L2
time frame: Up to 1 year
measure: Tumor expression of cancer/testis antigens such as PRAME
time frame: Up to 1 year
measure: Type of breast cancer (estrogen receptor [ER] positive, HER2 positive, triple negative)
time frame: Up to 1 year
measure: Edmonton Symptom Assessment Survey
time frame: Up to 1 year
description: Assessment of nine symptoms commonly seen in cancer patients. Patients rate on scale of 0-10 with 0 meaning the symptom is absent and 10 meaning the worst possible severity.
arm group label: Treatment (SV-BR-1GM, pembrolizumab)
arm group type: Experimental
description: Patients receive cyclophosphamide IV over 1-2 hours on day 1, SV-BR-1-GM ID on day 3, pembrolizumab IV over 30 minutes on day 5, and interferon-alpha-2b ID on days 5 and 7. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Cyclophosphamide
description: alkylating agent used in the treatment of several forms of cancer including leukemias, lymphomas and breast cancer.
arm group label: Treatment (SV-BR-1GM, pembrolizumab)
intervention type: Biological
intervention name: Allogeneic GM-CSF-secreting Breast Cancer Vaccine SV-BR-1-GM
description: Breast Cancer Vaccine SV-BR-1-GM, Bria-IMT, GM-CSF Gene-transfected Breast Cancer Vaccine SV-BR-1-GM, SV-BR-1 Breast Cancer Cell Line Vaccine, SV-BR-1-GM, SV-BR-1-GM Vaccine
arm group label: Treatment (SV-BR-1GM, pembrolizumab)
intervention type: Biological
intervention name: Pembrolizumab
description: 1374853-91-4, Immunoglobulin G4, Anti-(Human Programmed Cell Death 1); Humanized Mouse Monoclonal (228-L-proline(H10-S>P))gamma 4 Heavy Chain (134-218'')-disulfide with Humanized Mouse Monoclonal Kappa Light Chain Dimer (226-226'''':229-229'''')-bisdisulfide, Keytruda, Lambrolizumab, MK-3475, PEMBROLIZUMAB, SCH 900475
arm group label: Treatment (SV-BR-1GM, pembrolizumab)
intervention type: Biological
intervention name: Recombinant Interferon Alpha 2b-like Protein
description: Novaferon, Recombinant IFN Alfa-2b-like Protein
arm group label: Treatment (SV-BR-1GM, pembrolizumab)
intervention type: Other
intervention name: Questionnaire Administration
description: Ancillary studies
arm group label: Treatment (SV-BR-1GM, pembrolizumab)
intervention type: Other
intervention name: Quality of Life Assessment
description: Ancillary studies
arm group label: Treatment (SV-BR-1GM, pembrolizumab)
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Breast Neoplasms
mesh term: Interferons
mesh term: Interferon-alpha
mesh term: Interferon alpha-2
mesh term: Cyclophosphamide
mesh term: Pembrolizumab