<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/NCT02229084</url>
  </required_header>
  <id_info>
    <org_study_id>202556</org_study_id>
    <nct_id>NCT02229084</nct_id>
  </id_info>
  <brief_title>Vaccination of High Risk Breast Cancer Patients</brief_title>
  <official_title>A Combined Phase I/II Feasibility-and-Efficacy Study of a Carbohydrate Mimotope-based Vaccine With MONTANIDE™ ISA 51 VG Combined With Neoadjuvant Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Arkansas</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Arkansas</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>
      The purpose of this study is to evaluate a new investigational cancer vaccine, P10s-PADRE in&#xD;
      combination with standard neoadjuvant chemotherapy and surgery in patients with clinical&#xD;
      stage I, II or III estrogen-receptor (ER)-positive, HER2-negative breast cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this study is to evaluate an investigational agent, P10s-PADRE, a peptide&#xD;
      mimotope-based vaccine, in combination with standard neoadjuvant chemotherapy in patients&#xD;
      with clinical stage I, II or III estrogen-receptor (ER)-positive, HER2-negative breast&#xD;
      cancer.&#xD;
&#xD;
      This is a single-arm, multi-site Phase I/II study designed with the two goals being (1) to&#xD;
      evaluate the feasibility of combining vaccination with the P10s-PADRE formulation with&#xD;
      neoadjuvant chemotherapy and (2) to determine if the polymerase chain reaction (pCR) rate&#xD;
      among ER-positive, HER2-negativebreast-cancer patients treated with the combination is&#xD;
      significantly higher than the 8% rate observed among ER-positive breast-cancer subjects in a&#xD;
      pooled analysis of seven randomized clinical trials. P10s-PADRE vaccine with MONTANIDE™ ISA&#xD;
      51 VG as adjuvant will be given in combination with neoadjuvant chemotherapy in female&#xD;
      patients with clinical stage I, II or III ER-positive, HER2-negative breast cancer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 14, 2015</start_date>
  <completion_date type="Actual">January 3, 2023</completion_date>
  <primary_completion_date type="Actual">January 3, 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>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>This combined Phase I/II feasibility-and-efficacy study will have three parts. Part 1 will be a Phase I evaluation of the safety, tolerability, and feasibility of the Chemovax to assess the timing of vaccination relative to chemotherapy. Five different Chemovax schedules (Schedule A, B, C, D, and E) will be sequentially evaluated. Once such a feasible schedule is identified, the study will proceed with its second and third parts. Part 2 (primary efficacy) and Part 3 (expanded efficacy) will respectively constitute Stages 1 and 2 of the Phase II primary-efficacy evaluation of Chemovax using a Simon optimal two-stage design.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Identify a feasible schedule of vaccination relative to SoC neoadjuvant chemotherapy when the Chemovax are administered concurrently.</measure>
    <time_frame>At the time of definitive surgery (4-8 weeks after chemo, which is between Week 22 and Week 25)</time_frame>
    <description>Number of participants with sufficiently high anti-P10s immunoglobulin-G response Feasibility will be evaluated in terms of&#xD;
Generation of a sufficiently high anti-P10s immunoglobulin-G response&#xD;
Safety and tolerability of the combination of vaccine and chemotherapy</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Demonstration of clinical response</measure>
    <time_frame>Week 73 (±4 weeks) per subject</time_frame>
    <description>Determine if the Chemovax regimen in ER-positive breast cancer would lead to a significantly higher rate of pCR in breast and axillary lymph nodes at time of definitive surgery compared to the corresponding rate reported by von Minckwitz et al.</description>
  </primary_outcome>
  <number_of_arms>7</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Breast Cancer</condition>
  <condition>Breast Neoplasms</condition>
  <arm_group>
    <arm_group_label>Part 1 - Chemovax Schedule A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Feasibility - Chemovax schedule A: Subjects will receive the first cycle of chemotherapy along with the first injection of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine on week 1, the subsequent two injections of the vaccine one week apart (week 2 and 3), second cycle of chemotherapy on week 4, and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1 - Chemovax Schedule B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Feasibility - Chemovax Schedule B: Subjects will receive the first cycle of chemotherapy on week 1, the first injection of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine on week 2, the subsequent two injections of the vaccine one week apart (week 3 and 4), second cycle of chemotherapy on week 4 (along with second vaccine injection) and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1 - Chemovax Schedule C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Feasibility - Chemovax Schedule C: Subjects will receive three weekly injections of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine (week 1,2,3), then first cycle of chemotherapy (week 4), and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22,25).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1 - Chemovax Schedule D</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Feasibility - Chemovax Schedule D: Subjects will receive the first injection of vaccine on week 1, the subsequent two injections of the P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine one week apart (week 2 and 3), the first cycle of chemotherapy on week 2 (along with second vaccine injection) and subsequent cycles of chemotherapy every 21 days (week 5,8,11,14,17,20,23).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1 - Chemovax Schedule E</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Feasibility - Chemovax Schedule E: Subjects will receive the first injection of vaccine on week 1, the subsequent two injections of the P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine one week apart (week 2 and 3), the first cycle of chemotherapy on week 3 (along with third vaccine injection) and subsequent cycles of chemotherapy every 21 days (week 6,9,12,15,18,21,24).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2 - Chemovax Schedule C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Primary Efficacy - Chemovax Schedule C: Subjects will receive three weekly injections of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine (week 1,2,3), then first cycle of chemotherapy (week 4), and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22,25).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 3 - Chemovax Schedule C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Expanded Efficacy - Chemovax Schedule C: Subjects will receive three weekly injections of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine (week 1,2,3), then first cycle of chemotherapy (week 4), and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22,25).</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or Paclitaxel)</intervention_name>
    <description>Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions over a three-week period.</description>
    <arm_group_label>Part 1 - Chemovax Schedule A</arm_group_label>
    <arm_group_label>Part 1 - Chemovax Schedule B</arm_group_label>
    <arm_group_label>Part 1 - Chemovax Schedule C</arm_group_label>
    <arm_group_label>Part 1 - Chemovax Schedule D</arm_group_label>
    <arm_group_label>Part 1 - Chemovax Schedule E</arm_group_label>
    <arm_group_label>Part 2 - Chemovax Schedule C</arm_group_label>
    <arm_group_label>Part 3 - Chemovax Schedule C</arm_group_label>
    <other_name>P10s-PADRE/ MONTANIDE™ ISA 51 VG with standard neoadjuvant chemotherapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Females of all races with clinical stage I, II, or III ER-positive, HER2 negative&#xD;
             breast cancer who will undergo SoC neoadjuvant treatment.&#xD;
&#xD;
          -  Age 18 years and older.&#xD;
&#xD;
          -  ECOG Performance Status 0 or 1.&#xD;
&#xD;
          -  White blood cell (WBC) count ≥ 3,000/mm3 within 3 weeks prior to registration.&#xD;
&#xD;
          -  Platelet count ≥ 100,000/mm3 within 3 weeks prior to registration.&#xD;
&#xD;
          -  Bilirubin ≤ 2 x institutional upper limit (IUL) of normal obtained within 3 weeks&#xD;
             prior to registration.&#xD;
&#xD;
          -  Serum glutamic-oxaloacetic transaminase (SGOT) or aspartate aminotransferase test&#xD;
             (AST) ≤ 2 x IUL of normal obtained within 3 weeks prior to registration.&#xD;
&#xD;
          -  Serum glutamic-pyruvic transaminase (SGPT) or alanine aminotransferase test (ALT) ≤ 2&#xD;
             x IUL of normal obtained within 3 weeks prior to registration.&#xD;
&#xD;
          -  Serum creatinine ≤ 1.8 mg/dL obtained within 3 weeks prior to registration.&#xD;
&#xD;
          -  Must sign an informed consent document approved by the UAMS IRB.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  ER-negative, HER2-positive, inflammatory, metastatic, stage IV or recurrent breast&#xD;
             cancer&#xD;
&#xD;
          -  Active infection requiring treatment with antibiotics.&#xD;
&#xD;
          -  Existing diagnosis or history of organic brain syndrome that might preclude&#xD;
             participation in the full protocol.&#xD;
&#xD;
          -  Existing diagnosis or history of significant impairment of basal cognitive function&#xD;
             that might preclude participation in the full protocol.&#xD;
&#xD;
          -  Other current malignancies. Subjects with prior history at any time of any in situ&#xD;
             cancer, including lobular carcinoma of the breast in situ, cervical cancer in situ,&#xD;
             atypical melanocytic hyperplasia or Clark I melanoma in situ or basal or squamous skin&#xD;
             cancer are eligible, provided they are disease-free at the time of registration.&#xD;
             Subjects with other malignancies are eligible if they have been continuously disease&#xD;
             free for ≥ 5 years prior to the time of registration.&#xD;
&#xD;
          -  Active autoimmune disorders or conditions of immunosuppression; Existing diagnosis or&#xD;
             history of autoimmune disorders or conditions of immunosuppression that have been in&#xD;
             remission for less than 6 months&#xD;
&#xD;
          -  Treatment with corticosteroids, including oral steroids (i.e. prednisone,&#xD;
             dexamethasone [except when used as an antiemetic in SoC therapy]), continuous use of&#xD;
             topical steroid creams or ointments or any steroid-containing inhalers. Subjects who&#xD;
             discontinue the use of these classes of medication for at least 6 weeks prior to&#xD;
             registration are eligible if, in the judgment of the treating physician, the subject&#xD;
             is not likely to require these classes of drugs during the treatment period.&#xD;
             Replacement doses of steroids for subjects with adrenal insufficiency are allowed.&#xD;
&#xD;
          -  Pregnancy or breastfeeding (due to the unknown effects of peptide/mimotope vaccines on&#xD;
             a fetus or infant). Women of childbearing potential must have a negative urine&#xD;
             pregnancy test within 72 hours prior to starting week 1 and must be counseled to use&#xD;
             an accepted and effective method of contraception (including abstinence) while on&#xD;
             treatment and for a period of 18 months after completing or discontinuing treatment.&#xD;
             Accepted methods of contraception include tubal ligation, oral contraceptives, barrier&#xD;
             methods, IUDs, and abstinence.&#xD;
&#xD;
          -  Any other significant medical or psychiatric conditions, which, in the opinion of the&#xD;
             enrolling investigator, may interfere with consent or compliance of the treatment&#xD;
             regimen.&#xD;
&#xD;
          -  Enrollment in any other clinical trial using investigational drug products or devices&#xD;
             prior to first post-surgery study lab. Concurrent enrollment in observational studies&#xD;
             is allowed.&#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>Sindhu Malapati, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Arkansas</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Highlands Oncology Group</name>
      <address>
        <city>Fayetteville</city>
        <state>Arkansas</state>
        <zip>72703</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Arkansas for Medical Sciences</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>August 26, 2014</study_first_submitted>
  <study_first_submitted_qc>August 27, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 29, 2014</study_first_posted>
  <last_update_submitted>January 26, 2023</last_update_submitted>
  <last_update_submitted_qc>January 26, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 30, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>clinical stage I, II or III</keyword>
  <keyword>ER postive</keyword>
  <keyword>HER2 negative</keyword>
  <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>Paclitaxel</mesh_term>
    <mesh_term>Docetaxel</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Monatide (IMS 3015)</mesh_term>
    <mesh_term>Freund's Adjuvant</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/NCT02229084
org study id: 202556
nct id: NCT02229084
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate a new investigational cancer vaccine, P10s-PADRE in
      combination with standard neoadjuvant chemotherapy and surgery in patients with clinical
      stage I, II or III estrogen-receptor (ER)-positive, HER2-negative breast cancer.
The purpose of this study is to evaluate an investigational agent, P10s-PADRE, a peptide
      mimotope-based vaccine, in combination with standard neoadjuvant chemotherapy in patients
      with clinical stage I, II or III estrogen-receptor (ER)-positive, HER2-negative breast
      cancer.

      This is a single-arm, multi-site Phase I/II study designed with the two goals being (1) to
      evaluate the feasibility of combining vaccination with the P10s-PADRE formulation with
      neoadjuvant chemotherapy and (2) to determine if the polymerase chain reaction (pCR) rate
      among ER-positive, HER2-negativebreast-cancer patients treated with the combination is
      significantly higher than the 8% rate observed among ER-positive breast-cancer subjects in a
      pooled analysis of seven randomized clinical trials. P10s-PADRE vaccine with MONTANIDE™ ISA
      51 VG as adjuvant will be given in combination with neoadjuvant chemotherapy in female
      patients with clinical stage I, II or III ER-positive, HER2-negative breast cancer.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: This combined Phase I/II feasibility-and-efficacy study will have three parts. Part 1 will be a Phase I evaluation of the safety, tolerability, and feasibility of the Chemovax to assess the timing of vaccination relative to chemotherapy. Five different Chemovax schedules (Schedule A, B, C, D, and E) will be sequentially evaluated. Once such a feasible schedule is identified, the study will proceed with its second and third parts. Part 2 (primary efficacy) and Part 3 (expanded efficacy) will respectively constitute Stages 1 and 2 of the Phase II primary-efficacy evaluation of Chemovax using a Simon optimal two-stage design.
primary purpose: Treatment
masking: None (Open Label)
measure: Identify a feasible schedule of vaccination relative to SoC neoadjuvant chemotherapy when the Chemovax are administered concurrently.
time frame: At the time of definitive surgery (4-8 weeks after chemo, which is between Week 22 and Week 25)
description: Number of participants with sufficiently high anti-P10s immunoglobulin-G response Feasibility will be evaluated in terms of
Generation of a sufficiently high anti-P10s immunoglobulin-G response
Safety and tolerability of the combination of vaccine and chemotherapy
measure: Demonstration of clinical response
time frame: Week 73 (±4 weeks) per subject
description: Determine if the Chemovax regimen in ER-positive breast cancer would lead to a significantly higher rate of pCR in breast and axillary lymph nodes at time of definitive surgery compared to the corresponding rate reported by von Minckwitz et al.
arm group label: Part 1 - Chemovax Schedule A
arm group type: Experimental
description: Feasibility - Chemovax schedule A: Subjects will receive the first cycle of chemotherapy along with the first injection of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine on week 1, the subsequent two injections of the vaccine one week apart (week 2 and 3), second cycle of chemotherapy on week 4, and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22).
arm group label: Part 1 - Chemovax Schedule B
arm group type: Experimental
description: Feasibility - Chemovax Schedule B: Subjects will receive the first cycle of chemotherapy on week 1, the first injection of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine on week 2, the subsequent two injections of the vaccine one week apart (week 3 and 4), second cycle of chemotherapy on week 4 (along with second vaccine injection) and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22).
arm group label: Part 1 - Chemovax Schedule C
arm group type: Experimental
description: Feasibility - Chemovax Schedule C: Subjects will receive three weekly injections of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine (week 1,2,3), then first cycle of chemotherapy (week 4), and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22,25).
arm group label: Part 1 - Chemovax Schedule D
arm group type: Experimental
description: Feasibility - Chemovax Schedule D: Subjects will receive the first injection of vaccine on week 1, the subsequent two injections of the P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine one week apart (week 2 and 3), the first cycle of chemotherapy on week 2 (along with second vaccine injection) and subsequent cycles of chemotherapy every 21 days (week 5,8,11,14,17,20,23).
arm group label: Part 1 - Chemovax Schedule E
arm group type: Experimental
description: Feasibility - Chemovax Schedule E: Subjects will receive the first injection of vaccine on week 1, the subsequent two injections of the P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine one week apart (week 2 and 3), the first cycle of chemotherapy on week 3 (along with third vaccine injection) and subsequent cycles of chemotherapy every 21 days (week 6,9,12,15,18,21,24).
arm group label: Part 2 - Chemovax Schedule C
arm group type: Experimental
description: Primary Efficacy - Chemovax Schedule C: Subjects will receive three weekly injections of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine (week 1,2,3), then first cycle of chemotherapy (week 4), and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22,25).
arm group label: Part 3 - Chemovax Schedule C
arm group type: Experimental
description: Expanded Efficacy - Chemovax Schedule C: Subjects will receive three weekly injections of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine (week 1,2,3), then first cycle of chemotherapy (week 4), and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22,25).
intervention type: Biological
intervention name: Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or Paclitaxel)
description: Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions over a three-week period.
arm group label: Part 1 - Chemovax Schedule A
arm group label: Part 1 - Chemovax Schedule B
arm group label: Part 1 - Chemovax Schedule C
arm group label: Part 1 - Chemovax Schedule D
arm group label: Part 1 - Chemovax Schedule E
arm group label: Part 2 - Chemovax Schedule C
arm group label: Part 3 - Chemovax Schedule C
other name: P10s-PADRE/ MONTANIDE™ ISA 51 VG with standard neoadjuvant chemotherapy
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sindhu Malapati, MD
role: Principal Investigator
affiliation: University of Arkansas
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Paclitaxel
mesh term: Docetaxel
mesh term: Cyclophosphamide
mesh term: Doxorubicin
mesh term: Monatide (IMS 3015)
mesh term: Freund's Adjuvant