Clinical Trials /

Pilot Study of a Breast Cancer Vaccine Plus Poly-ICLC for Breast Cancer

NCT01532960

Description:

Despite advances in surgical, radiation and medical therapies of early stage breast cancer, some patients will experience disease recurrence. Because recurrence may not happen for years after definitive treatment, there is a period of time between resection and relapse when micrometastatic disease may be amenable to immune eradication or modulation. While the ultimate goal of any cancer treatment is clinical efficacy, the immediate urgency in breast immunotherapy is to define treatments that have immunologic efficacy. In this study, the investigators will determine whether a vaccine consisting of nine-class I breast specific peptides plus a class II tetanus toxoid helper peptide is immunogenic when administered with poly-ICLC to participants with stage IB to IIIA breast cancer in the adjuvant setting.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Pilot Study of a Breast Cancer Vaccine Plus Poly-ICLC for Breast Cancer
  • Official Title: A Pilot Study of the Immunogenicity of a 9-Peptide Breast Cancer Vaccine Plus Poly-ICLC in Stage I-IV Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 15881
  • NCT ID: NCT01532960

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
poly-ICLC9 Peptides from Her-2/neu, CEA, & CTA, peptide-tet, poly-ICLC
9 Peptides from Her-2/neu, CEA, & CTA9 Peptides from Her-2/neu, CEA, & CTA, peptide-tet, poly-ICLC
Peptide-tet9 Peptides from Her-2/neu, CEA, & CTA, peptide-tet, poly-ICLC

Purpose

Despite advances in surgical, radiation and medical therapies of early stage breast cancer, some patients will experience disease recurrence. Because recurrence may not happen for years after definitive treatment, there is a period of time between resection and relapse when micrometastatic disease may be amenable to immune eradication or modulation. While the ultimate goal of any cancer treatment is clinical efficacy, the immediate urgency in breast immunotherapy is to define treatments that have immunologic efficacy. In this study, the investigators will determine whether a vaccine consisting of nine-class I breast specific peptides plus a class II tetanus toxoid helper peptide is immunogenic when administered with poly-ICLC to participants with stage IB to IIIA breast cancer in the adjuvant setting.

Detailed Description

      The study is a single arm, open label, pilot study of safety and immune efficacy of peptide
      vaccination with poly-ICLC in patients with stage IB-IIIA resected breast cancer.
      Participants will be patients who have completed their last dose/treatment of any single
      treatment or combination of adjuvant surgery, radiation, chemotherapy or trastuzumab therapy
      between 45 days and 6 months (180 days) prior to enrollment.

      Each vaccination will be administered on days 1, 8, 15, 36, 57, and 78. All participants will
      receive 9 class I MHC-restricted synthetic peptides (restricted by HLA-A1, -A2, -A3, or -A31)
      and a class II MHC-restricted tetanus helper peptide mixed with 1mg poly-ICLC and
      administered in sterile water. The vaccine will be administered intramuscular (IM) (1 ml) and
      intradermally (ID) (1 ml) at vaccination sites in the arm and leg. (Each vaccine given IM and
      ID at one site; site to alternate between arm site opposite the breast cancer and an anterior
      thigh site.) Participants will be screened for HLA type and must be HLA-A1, -A2, -A3, or -A31
      (80% of the Virginia population in prior studies1).

      Annual follow-up for progression and survival for 3 years after study withdrawal/completion.
    

Trial Arms

NameTypeDescriptionInterventions
9 Peptides from Her-2/neu, CEA, & CTA, peptide-tet, poly-ICLCExperimental9 class I MHC-restricted synthetic peptides (100 mcg each peptide) derived from breast cancer associated proteins, a class II MHC-restricted tetanus derived peptide (200 mcg), plus polyICLC (1 mg).

    Eligibility Criteria

            Inclusion:
    
              -  Patients who have been diagnosed with clinical or pathologic stage I to stage IV
                 adenocarcinoma of the breast (any subtype) who have undergone, and recovered from
                 primary therapy (any combination of surgery, radiation, and/or chemotherapy and/or
                 HER2-directed therapy), with their last dose/treatment (of any single or combination
                 treatment) being between 28 days and 36 months prior to enrollment. Staging will be
                 based on the Seventh Edition AJCC staging system. (Systemic staging with CT or PET
                 scans is not required by AJCC and is not required or exclusionary for this trial).
    
              -  Stage IA patients must be high risk based upon triple negative status or HER2+ status
    
              -  Patients may or may not be receiving hormonal therapy at the time of study entry.
    
              -  Age ≥ 18 years at the time of enrollment
    
              -  ECOG performance status of 0 or 1
    
              -  Ability and willingness to give informed consent
    
              -  HLA-A1, -A2, -A3, or -A31 positive
    
              -  Adequate organ function
    
              -  HIV and Hepatitis C negative
    
              -  Subjects must have a minimum of two intact lymph node basins (any combination of
                 axillary and inguinal basins that have not undergone complete nodal dissection)
    
            Exclusion Criteria
    
              -  Known or suspected allergies to any component of the vaccine
    
              -  Active infection requiring antibiotics are excluded.
    
              -  The following medications or treatments within the 4 weeks (28 days) prior to
                 consenting. These medication and treatments may not be re-started at any time
                 throughout the study in order to remain eligible.
    
                   -  Breast tumor resection surgery (reconstructive surgery permitted)
    
                   -  Chemotherapy
    
                   -  Radiation therapy
    
                   -  Allergy desensitization injections
    
                   -  Growth factors (e.g., Procrit®, Aranesp®, Neulasta®)
    
                   -  Other agents with putative immunomodulating activity (with the exception of
                      non-steroidal anti-inflammatory agents)
    
                   -  Any investigational medication
    
              -  Tthe following medications or treatments within the 4 weeks (28 days) prior to
                 consenting:
    
                   -  Corticosteroids, administered parenterally, orally, or inhaled (Inhaled steroids,
                      such as: Advair®, Flovent®, Azmacort.®)
    
                   -  Topical corticosteroids are acceptable.
    
              -  Previous vaccination with any of the synthetic peptides included in this protocol.
    
              -  Active tuberculosis and not on active antitubercular agents
    
              -  Pregnancy.
    
              -  Female subjects must not be breastfeeding
    
              -  A medical contraindication or potential problem in complying with the requirements of
                 the protocol, in the opinion of the investigator
    
              -  New York Heart Association classification as having Class III or IV heart disease
    
              -  Stage IV subjects who have anticipated chemotherapy need within the 108 day treatment
                 period for this trial.
    
              -  Subjects that have experienced active autoimmune disorders requiring cytotoxic or
                 immunosuppressive therapy within the 6 weeks (42 days) prior to consenting.
    
                   -  The following will not be exclusionary:
    
                        -  The presence of laboratory evidence of autoimmune disease (e.g., positive
                           ANA titer) without symptoms
    
                        -  Clinical evidence of vitiligo
    
                        -  Other forms of depigmenting illness
    
                        -  Mild arthritis requiring NSAID medications
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Safety (Frequency of dose limiting adverse events)
    Time Frame:30 days post-administration of the last vaccine
    Safety Issue:
    Description:Measured as the number of IFN-gamma producing cells in the blood in response to the vaccine.

    Secondary Outcome Measures

    Measure:Safety (adverse event profile)
    Time Frame:30 days post-administration of the last vaccine
    Safety Issue:
    Description:
    Measure:Immunogenicity- CD8+ T cell specificity
    Time Frame:through day 108
    Safety Issue:
    Description:Characterize vaccine specific peripheral CD8+ T-cell specificity by tetramer staining and flow cytometric analysis
    Measure:Immunogenicity- CD8+ cytokine production
    Time Frame:through day 108
    Safety Issue:
    Description:Estimate the Tc1/Tc2 cytokine production bias of circulating vaccine-specific T cells.
    Measure:Immunogenicity- immue responses among subjects treated with anti-estrogen therapies
    Time Frame:through day 108
    Safety Issue:
    Description:Using the ELIspot assay, describe the frequency of immune responses among patients treated with anti-estrogen therapies

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Terminated
    Lead Sponsor:Craig L Slingluff, Jr

    Trial Keywords

    • breast cancer
    • peptide vaccine
    • immunotherapy

    Last Updated

    August 11, 2016