<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/NCT03012100</url>
  </required_header>
  <id_info>
    <org_study_id>RU011501I</org_study_id>
    <secondary_id>NCI-2016-01878</secondary_id>
    <secondary_id>RU011501I</secondary_id>
    <secondary_id>P30CA015083</secondary_id>
    <nct_id>NCT03012100</nct_id>
  </id_info>
  <brief_title>Multi-epitope Folate Receptor Alpha Peptide Vaccine, GM-CSF, and Cyclophosphamide in Treating Patients With Triple Negative Breast Cancer</brief_title>
  <official_title>Double Blind, Parallel Groups, Controlled, Randomized Phase II Trial to Evaluate Vaccination With Folate Receptor Alpha Peptide Vaccine With GM-CSF as Vaccine Adjuvant Following Oral Cyclophosphamide Versus GM-CSF/Placebo to Prevent Recurrence in Patients With Triple Negative Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Academic and Community Cancer Research United</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Academic and Community Cancer Research United</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 randomized phase II trial studies how well multi-epitope folate receptor alpha peptide&#xD;
      vaccine, sargramostim (GM-CSF), and cyclophosphamide work to prevent the recurrence of stage&#xD;
      1-3 triple negative breast cancer. Vaccines made from a person's white blood cells mixed with&#xD;
      tumor proteins may help the body build an effective immune response to kill tumor cells.&#xD;
      Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the&#xD;
      growth of tumor cells, either by killing the cells, by stopping them from dividing, or by&#xD;
      stopping them from spreading. Giving multi-epitope folate receptor alpha peptide vaccine,&#xD;
      sargramostim (GM-CSF), and cyclophosphamide may work well together to prevent cancer&#xD;
      recurrence after surgery and other standard treatments for triple negative breast cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To show that multi-epitope folate receptor alpha peptide vaccine (folate receptor&#xD;
      [FR]alpha peptide vaccine) with sargramostim (GM-CSF) adjuvant will prolong the disease-free&#xD;
      survival (DFS) compared to GM-CSF adjuvant treatment in patients with triple negative breast&#xD;
      cancer.&#xD;
&#xD;
      SECONDARY OBJECTIVE:&#xD;
&#xD;
      I. To compare the safety and tolerability of metronomic cyclophosphamide followed by FRalpha&#xD;
      peptide vaccine with GM-CSF versus GM-CSF alone.&#xD;
&#xD;
      CORRELATIVE RESEARCH OBJECTIVES:&#xD;
&#xD;
      I. To determine whether high level of antibody and cellular immune response toward the&#xD;
      FRalpha measured at baseline is a prognostic factor for vaccine immune response and/or cancer&#xD;
      relapse.&#xD;
&#xD;
      II. To determine whether the level of tumor expression of FRalpha at baseline is a prognosis&#xD;
      factor for vaccine immune response and/or cancer relapse.&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 2 arms.&#xD;
&#xD;
      ARM I: Patients receive cyclophosphamide orally (PO) twice daily (BID) on days 1-7 and 15-21&#xD;
      of cycle 1 only. Starting cycle 2, patients receive multi-epitope folate receptor alpha&#xD;
      peptide vaccine with sargramostim intradermally (ID) on day 1. Treatment repeats every 28&#xD;
      days for cycles 2-7 and every 6 months for cycles 8-14 in the absence of disease progression&#xD;
      or unacceptable toxicity.&#xD;
&#xD;
      ARM II: Patients receive cyclophosphamide as in Arm I. Starting cycle 2, patients receive&#xD;
      placebo vaccine with sargramostim ID on day 1. Treatment repeats every 28 days for cycles 2-7&#xD;
      and every 6 months for cycles 8-14 in the absence of disease progression or unacceptable&#xD;
      toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 6 months for 3 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 31, 2017</start_date>
  <completion_date type="Anticipated">July 31, 2026</completion_date>
  <primary_completion_date type="Actual">August 30, 2022</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Disease-free survival</measure>
    <time_frame>Through study completion (average of 5 years)</time_frame>
    <description>Will be estimated using the method of Kaplan-Meier. Will use the stratified log-rank tests.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events assessed by Common Terminology Criteria for Adverse Events 4.0</measure>
    <time_frame>Through study completion (average of 5 years)</time_frame>
    <description>The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed by primary disease site to determine toxicity patterns. Will use the Cochran-Mantel Haenszel chi-squared test with study stratification factors. Will use logistic regression to test differences in proportions while controlling for the known covariates.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Through study completion (average of 5 years)</time_frame>
    <description>Will be estimated using the method of Kaplan-Meier. Will use the stratified log-rank tests.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vaccine induced folate receptor [FR]alpha-specific T cell responses defined as the proportion of patients with at least a 2-fold increase in the number of cells/plasma concentration</measure>
    <time_frame>Through study completion (average of 5 years)</time_frame>
    <description>Will be determined along with its corresponding 95% confidence interval.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>FRalpha levels</measure>
    <time_frame>Through study completion (average of 5 years)</time_frame>
    <description>FRalpha levels at baseline will be examined as a prognostic factor in the vaccine immune response. A multivariable Cox proportional hazard model will be used to assess baseline FRalpha levels as a potential prognostic factor for immune response.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">280</enrollment>
  <condition>Bilateral Breast Carcinoma</condition>
  <condition>Breast Inflammatory Carcinoma</condition>
  <condition>Stage IB Breast Cancer AJCC v7</condition>
  <condition>Stage II Breast Cancer AJCC v6 and v7</condition>
  <condition>Stage IIA Breast Cancer AJCC v6 and v7</condition>
  <condition>Stage IIB Breast Cancer AJCC v6 and v7</condition>
  <condition>Stage III Breast Cancer AJCC v7</condition>
  <condition>Stage IIIA Breast Cancer AJCC v7</condition>
  <condition>Stage IIIB Breast Cancer AJCC v7</condition>
  <condition>Stage IIIC Breast Cancer AJCC v7</condition>
  <condition>Triple-Negative Breast Carcinoma</condition>
  <condition>Unilateral Breast Carcinoma</condition>
  <arm_group>
    <arm_group_label>Arm I (FRalpha peptide vaccine, sargramostim)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive cyclophosphamide PO BID on days 1-7 and 15-21 of cycle 1 only. Starting cycle 2, patients receive multi-epitope folate receptor alpha peptide vaccine with sargramostim ID on day 1. Treatment repeats every 28 days for cycles 2-7 and every 6 months for cycles 8-14 in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (placebo, sargramostim)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients receive cyclophosphamide as in Arm I. Starting cycle 2, patients receive placebo vaccine with sargramostim ID on day 1. Treatment repeats every 28 days for cycles 2-7 and every 6 months for cycles 8-14 in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm I (FRalpha peptide vaccine, sargramostim)</arm_group_label>
    <arm_group_label>Arm II (placebo, sargramostim)</arm_group_label>
    <other_name>(-)-Cyclophosphamide</other_name>
    <other_name>2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate</other_name>
    <other_name>Carloxan</other_name>
    <other_name>Ciclofosfamida</other_name>
    <other_name>Ciclofosfamide</other_name>
    <other_name>Cicloxal</other_name>
    <other_name>Clafen</other_name>
    <other_name>Claphene</other_name>
    <other_name>CP monohydrate</other_name>
    <other_name>CTX</other_name>
    <other_name>CYCLO-cell</other_name>
    <other_name>Cycloblastin</other_name>
    <other_name>Cycloblastine</other_name>
    <other_name>Cyclophospham</other_name>
    <other_name>Cyclophosphamid monohydrate</other_name>
    <other_name>Cyclophosphamide Monohydrate</other_name>
    <other_name>Cyclophosphamidum</other_name>
    <other_name>Cyclophosphan</other_name>
    <other_name>Cyclophosphane</other_name>
    <other_name>Cyclophosphanum</other_name>
    <other_name>Cyclostin</other_name>
    <other_name>Cyclostine</other_name>
    <other_name>Cytophosphan</other_name>
    <other_name>Cytophosphane</other_name>
    <other_name>Cytoxan</other_name>
    <other_name>Fosfaseron</other_name>
    <other_name>Genoxal</other_name>
    <other_name>Genuxal</other_name>
    <other_name>Ledoxina</other_name>
    <other_name>Mitoxan</other_name>
    <other_name>Neosar</other_name>
    <other_name>Revimmune</other_name>
    <other_name>Syklofosfamid</other_name>
    <other_name>WR- 138719</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Arm I (FRalpha peptide vaccine, sargramostim)</arm_group_label>
    <arm_group_label>Arm II (placebo, sargramostim)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Multi-epitope Folate Receptor Alpha Peptide Vaccine</intervention_name>
    <description>Given ID</description>
    <arm_group_label>Arm I (FRalpha peptide vaccine, sargramostim)</arm_group_label>
    <other_name>FR Alpha Peptide Vaccine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo Administration</intervention_name>
    <description>Given ID</description>
    <arm_group_label>Arm II (placebo, sargramostim)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Sargramostim</intervention_name>
    <description>Given ID</description>
    <arm_group_label>Arm I (FRalpha peptide vaccine, sargramostim)</arm_group_label>
    <arm_group_label>Arm II (placebo, sargramostim)</arm_group_label>
    <other_name>23-L-Leucinecolony-Stimulating Factor 2</other_name>
    <other_name>DRG-0012</other_name>
    <other_name>Leukine</other_name>
    <other_name>Prokine</other_name>
    <other_name>rhu GM-CFS</other_name>
    <other_name>Sagramostim</other_name>
    <other_name>Sargramostatin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt;= 18 years&#xD;
&#xD;
          -  Female&#xD;
&#xD;
          -  Resected unilateral or bilateral primary carcinoma of the breast without clinical&#xD;
             evidence of metastatic disease (after neoadjuvant chemotherapy and/or adjuvant&#xD;
             chemotherapy), negative for estrogen receptor (ER) and progesterone receptor (PR)&#xD;
             (cut-off for positivity is &gt; 10% positive tumor cells with nuclear staining), and&#xD;
             negative for HER2 as defined by one of the four situations delineated below:&#xD;
&#xD;
               -  HER2 immunohistochemistry (IHC) expression of 0 or 1+ and in-situ hybridization&#xD;
                  non-amplified&#xD;
&#xD;
               -  HER2 IHC expression of 0 or 1+ and in-situ hybridization not done&#xD;
&#xD;
               -  HER2 IHC expression of 2+ and in-situ hybridization non-amplified&#xD;
&#xD;
               -  IHC not done and in-situ hybridization non-amplified&#xD;
&#xD;
               -  Note: central review is not required&#xD;
&#xD;
               -  Note: If biopsy and surgical specimens are discordant from each other with regard&#xD;
                  to ER, PR, and/or HER2 status, a patient will be allowed to enroll assuming at&#xD;
                  least one of the specimens meets the above criteria and no endocrine therapy use&#xD;
                  is planned going forward&#xD;
&#xD;
          -  Completed planned breast CANCER surgeries, any radiation therapy, and any&#xD;
             chemotherapy, whichever is last, &gt;= 90 days but not &gt;= 546 days prior to randomization&#xD;
&#xD;
               -  Note: Reconstructive and prophylactic surgeries are allowed after randomization&#xD;
                  (during study treatment)&#xD;
&#xD;
          -  Patient had at least one of the following:&#xD;
&#xD;
               -  Biopsy or surgery-proven regional node involvement by cancer&#xD;
&#xD;
               -  T1c, T2, T3, or T4 disease (with inflammatory disease allowed) identified at the&#xD;
                  time of surgery or clinically identified prior to neoadjuvant chemotherapy&#xD;
&#xD;
               -  No complete response to neoadjuvant chemotherapy (those who did achieve complete&#xD;
                  response are still eligible if a pre-chemotherapy regional nodal biopsy&#xD;
                  identified cancer or if the pre-chemotherapy tumor measured &gt; 1 cm)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1500/mm^3 obtained =&lt; 14 days prior to&#xD;
             randomization&#xD;
&#xD;
          -  Platelet count &gt;= 75,000/uL obtained =&lt; 14 days prior to randomization&#xD;
&#xD;
          -  Aspartate transaminase (AST) =&lt; 3 x upper limit of normal (ULN) obtained =&lt; 14 days&#xD;
             prior to randomization&#xD;
&#xD;
          -  Creatinine =&lt; 1.5 x ULN obtained =&lt; 14 days prior to randomization&#xD;
&#xD;
          -  Negative serum pregnancy test done =&lt; 14 days prior to randomization, for women of&#xD;
             childbearing potential only&#xD;
&#xD;
          -  Provide informed written consent&#xD;
&#xD;
          -  Willing to return to enrolling institution for follow-up&#xD;
&#xD;
          -  Willing to provide tissue and blood samples for correlative research studies&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any of the following because this study involves an investigational agent whose&#xD;
             genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are&#xD;
             unknown:&#xD;
&#xD;
               -  Pregnant women&#xD;
&#xD;
               -  Nursing women&#xD;
&#xD;
               -  Women of childbearing potential who are unwilling to employ adequate&#xD;
                  contraception&#xD;
&#xD;
          -  Clinical evidence of local recurrence or distant metastases; Note: New primary tumors&#xD;
             are allowed, both contralaterally and ipsilaterally, but a prior breast cancer must&#xD;
             have been more than 5 years beforehand&#xD;
&#xD;
          -  Known hypersensitivity reaction to GM-CSF&#xD;
&#xD;
          -  Active autoimmune disease that has required systemic treatment =&lt; 30 days (i.e., with&#xD;
             use of disease modifying agents, corticosteroids, or immunosuppressive drugs) prior to&#xD;
             randomization; Note: replacement therapy (e.g., thyroxine, insulin, or physiologic&#xD;
             corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not&#xD;
             considered a form of systemic treatment; patients with vitiligo, Graves disease, or&#xD;
             psoriasis not requiring systemic treatment within the past 30 days are not excluded;&#xD;
             patients with Celiac disease controlled with diet modification are not excluded&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements&#xD;
&#xD;
               -  NOTE: Localized fungal or viral infections including of the skin, nails, mouth,&#xD;
                  and genital area are allowed&#xD;
&#xD;
          -  History of other cancer &lt; 5 years prior to consent (except non-melanoma skin cancer or&#xD;
             carcinoma in situ of the uterine cervix) or current receipt of treatment another&#xD;
             cancer (e.g., monoclonal antibody, small molecule pathway inhibitor)&#xD;
&#xD;
          -  Treatment with systemic corticosteroid or immune-modulators =&lt; 7 days prior to&#xD;
             randomization&#xD;
&#xD;
          -  Concurrent treatment with other experimental drugs or any other systemic anticancer&#xD;
             therapy (due to unknown drug-vaccine potential interactions). Use of experimental or&#xD;
             other targeted therapy &gt; 3 months prior is allowed as long as it is not Her2-directed&#xD;
&#xD;
               -  NOTE: Aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), statins, and other&#xD;
                  medications commonly used to treat nononcologic, non-autoimmune conditions are&#xD;
                  allowed&#xD;
&#xD;
          -  Immunocompromised patients and patients known to be human immunodeficiency virus (HIV)&#xD;
             positive and currently receiving antiretroviral therapy&#xD;
&#xD;
          -  Prior or concurrent use of trastuzumab or other Her2-directed therapy&#xD;
&#xD;
          -  Prior or concurrent use of a PD-1 or PD-L1 checkpoint inhibitor (including&#xD;
             pembrolizumab) unless the use was &gt;= 3 months prior to randomization&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kathryn J Ruddy</last_name>
    <role>Principal Investigator</role>
    <affiliation>Academic and Community Cancer Research United</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic in Arizona</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85259</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City of Hope Comprehensive Cancer Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic in Florida</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224-9980</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami Miller School of Medicine-Sylvester Cancer Center</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago Comprehensive Cancer Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carle Cancer Center NCI Community Oncology Research Program</name>
      <address>
        <city>Urbana</city>
        <state>Illinois</state>
        <zip>61801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ochsner Medical Center Jefferson</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70121</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital Cancer Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic in Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inova Fairfax Hospital</name>
      <address>
        <city>Falls Church</city>
        <state>Virginia</state>
        <zip>22042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marshfield Medical Center-Marshfield</name>
      <address>
        <city>Marshfield</city>
        <state>Wisconsin</state>
        <zip>54449</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>December 29, 2016</study_first_submitted>
  <study_first_submitted_qc>January 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 6, 2017</study_first_posted>
  <last_update_submitted>January 12, 2023</last_update_submitted>
  <last_update_submitted_qc>January 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 13, 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>Carcinoma</mesh_term>
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Triple Negative 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>Cyclophosphamide</mesh_term>
    <mesh_term>Vaccines</mesh_term>
    <mesh_term>Sargramostim</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/NCT03012100
org study id: RU011501I
secondary id: NCI-2016-01878
secondary id: RU011501I
secondary id: P30CA015083
nct id: NCT03012100
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This randomized phase II trial studies how well multi-epitope folate receptor alpha peptide
      vaccine, sargramostim (GM-CSF), and cyclophosphamide work to prevent the recurrence of stage
      1-3 triple negative breast cancer. Vaccines made from a person's white blood cells mixed with
      tumor proteins may help the body build an effective immune response to kill tumor cells.
      Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the
      growth of tumor cells, either by killing the cells, by stopping them from dividing, or by
      stopping them from spreading. Giving multi-epitope folate receptor alpha peptide vaccine,
      sargramostim (GM-CSF), and cyclophosphamide may work well together to prevent cancer
      recurrence after surgery and other standard treatments for triple negative breast cancer.
PRIMARY OBJECTIVE:

      I. To show that multi-epitope folate receptor alpha peptide vaccine (folate receptor
      [FR]alpha peptide vaccine) with sargramostim (GM-CSF) adjuvant will prolong the disease-free
      survival (DFS) compared to GM-CSF adjuvant treatment in patients with triple negative breast
      cancer.

      SECONDARY OBJECTIVE:

      I. To compare the safety and tolerability of metronomic cyclophosphamide followed by FRalpha
      peptide vaccine with GM-CSF versus GM-CSF alone.

      CORRELATIVE RESEARCH OBJECTIVES:

      I. To determine whether high level of antibody and cellular immune response toward the
      FRalpha measured at baseline is a prognostic factor for vaccine immune response and/or cancer
      relapse.

      II. To determine whether the level of tumor expression of FRalpha at baseline is a prognosis
      factor for vaccine immune response and/or cancer relapse.

      OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM I: Patients receive cyclophosphamide orally (PO) twice daily (BID) on days 1-7 and 15-21
      of cycle 1 only. Starting cycle 2, patients receive multi-epitope folate receptor alpha
      peptide vaccine with sargramostim intradermally (ID) on day 1. Treatment repeats every 28
      days for cycles 2-7 and every 6 months for cycles 8-14 in the absence of disease progression
      or unacceptable toxicity.

      ARM II: Patients receive cyclophosphamide as in Arm I. Starting cycle 2, patients receive
      placebo vaccine with sargramostim ID on day 1. Treatment repeats every 28 days for cycles 2-7
      and every 6 months for cycles 8-14 in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up every 6 months for 3 years.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Disease-free survival
time frame: Through study completion (average of 5 years)
description: Will be estimated using the method of Kaplan-Meier. Will use the stratified log-rank tests.
measure: Incidence of adverse events assessed by Common Terminology Criteria for Adverse Events 4.0
time frame: Through study completion (average of 5 years)
description: The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed by primary disease site to determine toxicity patterns. Will use the Cochran-Mantel Haenszel chi-squared test with study stratification factors. Will use logistic regression to test differences in proportions while controlling for the known covariates.
measure: Overall survival
time frame: Through study completion (average of 5 years)
description: Will be estimated using the method of Kaplan-Meier. Will use the stratified log-rank tests.
measure: Vaccine induced folate receptor [FR]alpha-specific T cell responses defined as the proportion of patients with at least a 2-fold increase in the number of cells/plasma concentration
time frame: Through study completion (average of 5 years)
description: Will be determined along with its corresponding 95% confidence interval.
measure: FRalpha levels
time frame: Through study completion (average of 5 years)
description: FRalpha levels at baseline will be examined as a prognostic factor in the vaccine immune response. A multivariable Cox proportional hazard model will be used to assess baseline FRalpha levels as a potential prognostic factor for immune response.
arm group label: Arm I (FRalpha peptide vaccine, sargramostim)
arm group type: Experimental
description: Patients receive cyclophosphamide PO BID on days 1-7 and 15-21 of cycle 1 only. Starting cycle 2, patients receive multi-epitope folate receptor alpha peptide vaccine with sargramostim ID on day 1. Treatment repeats every 28 days for cycles 2-7 and every 6 months for cycles 8-14 in the absence of disease progression or unacceptable toxicity.
arm group label: Arm II (placebo, sargramostim)
arm group type: Placebo Comparator
description: Patients receive cyclophosphamide as in Arm I. Starting cycle 2, patients receive placebo vaccine with sargramostim ID on day 1. Treatment repeats every 28 days for cycles 2-7 and every 6 months for cycles 8-14 in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Cyclophosphamide
description: Given PO
arm group label: Arm I (FRalpha peptide vaccine, sargramostim)
arm group label: Arm II (placebo, sargramostim)
other name: (-)-Cyclophosphamide
other name: 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
other name: Carloxan
other name: Ciclofosfamida
other name: Ciclofosfamide
other name: Cicloxal
other name: Clafen
other name: Claphene
other name: CP monohydrate
other name: CTX
other name: CYCLO-cell
other name: Cycloblastin
other name: Cycloblastine
other name: Cyclophospham
other name: Cyclophosphamid monohydrate
other name: Cyclophosphamide Monohydrate
other name: Cyclophosphamidum
other name: Cyclophosphan
other name: Cyclophosphane
other name: Cyclophosphanum
other name: Cyclostin
other name: Cyclostine
other name: Cytophosphan
other name: Cytophosphane
other name: Cytoxan
other name: Fosfaseron
other name: Genoxal
other name: Genuxal
other name: Ledoxina
other name: Mitoxan
other name: Neosar
other name: Revimmune
other name: Syklofosfamid
other name: WR- 138719
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Arm I (FRalpha peptide vaccine, sargramostim)
arm group label: Arm II (placebo, sargramostim)
intervention type: Biological
intervention name: Multi-epitope Folate Receptor Alpha Peptide Vaccine
description: Given ID
arm group label: Arm I (FRalpha peptide vaccine, sargramostim)
other name: FR Alpha Peptide Vaccine
intervention type: Other
intervention name: Placebo Administration
description: Given ID
arm group label: Arm II (placebo, sargramostim)
intervention type: Biological
intervention name: Sargramostim
description: Given ID
arm group label: Arm I (FRalpha peptide vaccine, sargramostim)
arm group label: Arm II (placebo, sargramostim)
other name: 23-L-Leucinecolony-Stimulating Factor 2
other name: DRG-0012
other name: Leukine
other name: Prokine
other name: rhu GM-CFS
other name: Sagramostim
other name: Sargramostatin
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kathryn J Ruddy
role: Principal Investigator
affiliation: Academic and Community Cancer Research United
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country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Breast Neoplasms
mesh term: Triple Negative Breast Neoplasms
mesh term: Inflammatory Breast Neoplasms
mesh term: Cyclophosphamide
mesh term: Vaccines
mesh term: Sargramostim