Clinical Trials /

Folate Receptor Alpha Peptide Vaccine With GM-CSF in Patients With Triple Negative Breast Cancer

NCT02593227

Description:

This Phase II trial evaluates the safety and immunogenicity of two doses of the Folate Receptor Alpha (FRα) peptide vaccine mixed with GM-CSF as a vaccine adjuvant, with or without a immune priming with cyclophosphamide, as a consolidation therapy after neoadjuvant or adjuvant treatment of patients with Stage IIb-III triple negative breast cancer (TNBC).

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Folate Receptor Alpha Peptide Vaccine With <span class="go-doc-concept go-doc-intervention">GM-CSF</span> in Patients With <span class="go-doc-concept go-doc-keyword">Triple Negative</span> Breast Cancer

Title

  • Brief Title: Folate Receptor Alpha Peptide Vaccine With GM-CSF in Patients With Triple Negative Breast Cancer
  • Official Title: A Randomized Multicenter Phase II Trial to Evaluate the Safety and Immunogenicity of Two Doses of Vaccination With Folate Receptor Alpha Peptides With GM-CSF in Patients With Triple Negative Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT02593227

    ORG ID: FRV-002

    Trial Conditions

    Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Cyclophosphamide Cytoxan Low dose FR vaccine + cyclophosphamide, High dose FR vaccine + cyclophosphamide

    Trial Purpose

    This Phase II trial evaluates the safety and immunogenicity of two doses of the Folate
    Receptor Alpha (FR) peptide vaccine mixed with GM-CSF as a vaccine adjuvant, with or
    without a immune priming with cyclophosphamide, as a consolidation therapy after neoadjuvant
    or adjuvant treatment of patients with Stage IIb-III triple negative breast cancer (TNBC).

    Detailed Description

    Triple negative breast cancers (TNBCs) occur in approximately 20-25% of all patients with
    breast cancer and are associated with a poor prognosis. Patients with TNBCs derive no
    benefit from targeted therapies. Excluding those patients who demonstrate a pathologic
    complete response following neoadjuvant chemotherapy, which is a minor fraction (i.e. 15%),
    overall survival is only 45% at 7 years.

    Following standard of care, there are windows of opportunity to further and safely treat
    patients to prevent recurrence. Stimulating the immune system to produce T cells immunity
    specific for tumor antigens may significantly delay recurrence and cure patients.

    The proposed vaccine is intended to induce T cells to survey for the reemergence of TNBCs
    and to prevent recurrence in the adjuvant setting. The vaccine strategy is antigen-specific
    and targets the Folate Receptor Alpha (FR). FR is an ideal target because of its limited
    expression in the healthy tissues and it high expression in 86% of TNBCs. Studies have shown
    that it is a biologically important marker that is associated with poorer clinical outcome
    and is retained in metastatic lesions.

    The FR vaccine include a pool of 5 peptides that are immunogenic epitopes and safely
    generate tissue-surveying CD4 T cell immune responses in patients tested in a recently
    completed phase I clinical trial.

    Trial Arms

    Name Type Description Interventions
    Low dose FR vaccine Experimental FR peptide vaccine with GM-CSF adjuvant - single ID administration - monthly vaccinations repeated 6 times followed by boosters every 6 months until recurrence
    High dose FR vaccine Experimental FR peptide vaccine with GM-CSF adjuvant - triple ID administration - monthly vaccinations repeated 6 times followed by boosters every 6 months until recurrence
    Low dose FR vaccine + cyclophosphamide Experimental Cyclophosphamide 300 mg/sqm as a 1 hour IV infusion 3 days prior to first vaccination. Followed by FR peptide vaccine with GM-CSF adjuvant - ID administration - monthly vaccinations repeated 6 times followed by boosters every 6 months until recurrence Cyclophosphamide
    High dose FR vaccine + cyclophosphamide Experimental Cyclophosphamide 300 mg/sqm as a 1 hour IV infusion 3 days prior to first vaccination. Followed by FR peptide vaccine with GM-CSF adjuvant - ID administration - monthly vaccinations repeated 6 times followed by boosters every 6 months until recurrence Cyclophosphamide

    Eligibility Criteria

    Inclusion Criteria:

    - Female patient, Age 18 years or older;

    - Written informed consent;

    - Negative for ER, PR and negative for Her2-neu (0 or 1+ on immunohistochemistry and/or
    normal gene copy number by fluorescence in-situ hybridization);

    - Completed surgery and radio/chemotherapy in adjuvant or neo-adjuvant setting <180
    days prior to consent.

    - Completed last cycle of chemotherapy or radiation > 60 days prior to consent

    - Unilateral or bilateral primary carcinoma of the breast with tumor Stage II-III
    according to AJCC 7th edition, and one of the following:

    1. For patient treated in the neoadjuvant setting: Histologically detectable tumor
    residuals (excludes ypT0/is ypN0), M0 and no evidence of gross tumor or gross
    residual adenopathy.

    2. For patients treated in the adjuvant setting: pN2-3 and M0. No evidence of gross
    tumor or gross residual adenopathy

    - Adequate Blood, renal and hepatic function, as determined within 28 days from
    enrollment:

    Exclusion Criteria:

    - Clinical evidence of distant metastases per practice guidelines for breast cancer;

    - Inflammatory breast cancer or tumor with deep adherence or cutaneous invasion;

    - Known hypersensitivity reaction to the GM-CSF adjuvant; Any known contra-indication
    to GM-CSF or Cyclophosphamide treatment;

    - Pregnant or lactating patients.

    - History of auto-immune diseases;

    - Other uncontrolled illness or medical condition , such as active infection,
    symptomatic heart failure, unstable angina pectoris, myocardial infarction or stroke
    within last 6 months, psychiatric illness that may limit compliance with study
    requirement or interfere with the understanding and giving of informed consent;

    - Prior active secondary malignancy < 5 years prior to consent (except non-melanomatous
    skin cancer or carcinoma in situ of the uterine cervix) or currently receiving other
    specific treatment for this cancer (including monoclonal antibody or pathway
    inhibitor);

    - Completed treatment with systemic corticosteroid or immune-modulators > 30 days prior
    to registration;

    - Planned treatment with other experimental drugs or any other anti-cancer therapy;

    - Immunocompromised patients including patients with known HIV infection;

    - Currently receiving thyroid replacement therapy.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Immune response

    Secondary Outcome Measures

    Folate receptor alpha expression

    Relapse Free Survival

    Safety and tolerability (treatment emergent adverse events and injection site reactions)

    Trial Keywords

    TNBC