Vaccine Therapy in Treating Patients With Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Antigen Express, Inc.
Norwell, Inc.
Information provided by (Responsible Party):
COL George Peoples, MD, FACS, San Antonio Military Medical Center
ClinicalTrials.gov Identifier:
NCT00524277
First received: August 31, 2007
Last updated: December 31, 2013
Last verified: December 2013

August 31, 2007
December 31, 2013
January 2007
December 2015   (final data collection date for primary outcome measure)
Disease recurrence [ Time Frame: Five years (from date of enrollment to the study through the end of the follow-up period) ] [ Designated as safety issue: No ]

The following will be compared:

  1. disease recurrence rates between HLA-A2-negative patients receiving the AE37 + GM-CSF vaccine and HLA-A2-negative patients receiving GM-CSF alone
  2. disease recurrence rates between HLA-A2-positive patients receiving the GP2 + GM-CSF vaccine and HLA-A2-positive patients receiving GM-CSF alone
  3. disease recurrence rates between all four arms of the trial.
Disease recurrence
Complete list of historical versions of study NCT00524277 on ClinicalTrials.gov Archive Site
  • Safety [ Time Frame: Local and systemic reactions to each inoculation will be monitored every six months during the regular inoculation series and the booster series. ] [ Designated as safety issue: Yes ]
    Inoculations will be immediately halted if any serious adverse reactions occur which, when based upon appropriate judgment of the PI, are determined to jeopardize the patient or require medical or surgical intervention. Any death or grade 4 adverse drug experience found to be directly related to the experimental vaccine will result in suspension of patient enrollment to the study.
  • Immune Response [ Time Frame: Immune response will be measured after every monthly inoculation in the regular inoculation series and after each inoculation in the booster series ] [ Designated as safety issue: No ]
    Immune response will be measured by proliferation assays, dimer assays, and ELISPOT. Delayed type hypersensitivity reactions will be compared between the vaccinated group and GM-CSF-only group.
  • Safety
  • Toxicity
Not Provided
Not Provided
 
Vaccine Therapy in Treating Patients With Breast Cancer
Phase II Trial of the HER2/Neu Peptide GP2 + GM-CSF Vaccine vs GM-CSF Alone in HLA-A2+ OR the Modified HER2/Neu Peptide AE37 + GM-CSF Vaccine vs GM-CSF Alone in HLA-A2- Node-Positive and High-Risk Node-Negative Breast Cancer Patients

RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill tumor cells that express HER2/neu. Biological therapies, such as GM-CSF, may stimulate the immune system in different ways and stop tumor cells from growing. It is not yet known whether vaccine therapy is more effective than GM-CSF in treating breast cancer.

PURPOSE: This randomized phase II trial is studying vaccine therapy to see how well it works compared with GM-CSF in treating patients with breast cancer.

OBJECTIVES:

  • To determine if the GP2 peptide/GM-CSF vaccine reduces the recurrence rate in HLA-A2-positive, HER2/neu-positive, node-positive, or high-risk node-negative breast cancer patients randomized to receive the vaccine versus the immunoadjuvant, sargramostim (GM-CSF), alone.
  • To determine if the AE37 peptide/GM-CSF vaccine reduces the recurrence rate in HLA-A2-negative, HER2/neu-positive, node-positive or high-risk node-negative breast cancer patients randomized to receive the vaccine versus the immunoadjuvant, GM-CSF, alone.
  • To monitor the invitro and invivo immunologic responses to the vaccines and correlate these responses with the clinical outcomes.
  • To monitor for any unexpected toxicities with the vaccines.

OUTLINE: This is a multicenter study. Patients are stratified according to nodal status. Patients are randomized to 1 of 4 treatment arms.

  • Arm I: HLA-A2-positive patients receive GP2 peptide/GM-CSF vaccine intradermally (ID) every 3-4 weeks for a total of up to 6 inoculations.
  • Arm II: HLA-A2-positive patients receive solely GM-CSF ID
  • Arm III: HLA-A2-negative patients receive AE37 peptide/GM-CSF vaccine ID every 3-4 weeks for a total of up to 6 inoculations.
  • Arm IV: HLA-A2-negative patients receive solely GM-CSF ID

After completion of study therapy, patients are followed every 3 months for the first 24 months and then every 6 months for an additional 36 months.

Booster inoculations are administered at 12, 18, 24, and 30 months from the date of patients' enrollment into the study. One booster inoculation is administered at each timepoint (+/- 2 weeks) and will be the same inoculation (vaccine or GM-CSF only) as what patients received during their regular inoculation series.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Prevention
Breast Cancer
  • Biological: GP2 peptide + GM-CSF vaccine
    Given intradermally every 3-4 weeks for a total of up to 6 inoculations
    Other Name: GM-CSF (sargramostim)
  • Biological: GM-CSF (sargramostim)
    GM-CSF given intradermally very 3-4 weeks for a total of up to 6 inoculations
    Other Name: GM-CSF (sargramostim)
  • Biological: AE37 + GM-CSF vaccine
    Given intradermally every 3-4 weeks for a total of up to 6 inoculations
    Other Name: GM-CSF (sargramostim)
  • Biological: GM-CSF (sargramostim)
    Given intradermally every 3-4 weeks for a total of up to 6 inoculations
    Other Name: GM-CSF (sargramostim)
  • Experimental: Arm I
    HLA-A2-positive patients receive GP2 peptide + GM-CSF vaccine intradermally (ID) every 3-4 weeks for a total of up to 6 inoculations.
    Intervention: Biological: GP2 peptide + GM-CSF vaccine
  • Active Comparator: Arm II
    HLA-A2-positive patients receive GM-CSF ID every 3-4 weeks for a total of up to 6 inoculations.
    Intervention: Biological: GM-CSF (sargramostim)
  • Experimental: Arm III
    HLA-A2-negative patients receive AE37 peptide/GM-CSF vaccine ID every 3-4 weeks for a total of up to 6 inoculations.
    Intervention: Biological: AE37 + GM-CSF vaccine
  • Active Comparator: Arm IV
    HLA-A2-negative patients receive GM-CSF ID ID every 3-4 weeks for a total of up to 6 inoculations
    Intervention: Biological: GM-CSF (sargramostim)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
600
December 2015
December 2015   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

Inclusion criteria:

  1. Lymph node-positive breast cancer or high-risk lymph node-negative breast cancer. The latter is defined by any one of the following criteria:

    • T2 disease
    • Grade 3 disease
    • Lymphovascular invasion
    • Estrogen receptor- or progesterone receptor-negative disease
    • HER2/neu-expressing tumor (immunohistochemistry [IHC] 3+ and/or amplified fluorescence in situ hybridization [FISH] >2.2, or N0 (i+))
  2. HER2/neu-expressing tumor (IHC 1-3+ and or positive FISH >1.2)
  3. Completion of primary standard of care breast cancer therapies (i.e., surgery, chemotherapy, immunotherapy and radiation therapy as appropriate per standard of care for patients' specific cancer)
  4. Clinically cancer-free (no evidence of disease)
  5. Patients may be enrolled between 1-6 months from completion of standard primary breast cancer therapies
  6. Good performance status (as defined in Exclusion Criteria)
  7. Capable of informed consent

Exclusion criteria:

  1. HER2/neu-negative breast cancers (IHC 0)
  2. Clinical and/or radiographic evidence of residual or persistent breast cancer
  3. Receiving immunosuppressive therapy to include chemotherapy, steroids, or methotrexate
  4. In poor health (Karnofsky <60%, ECOG >/-2)
  5. Total bilirubin >1.8, creatinine >2, hemoglobin <10, platelets <50,000, WBC <2,000)
  6. Active interstitial lung disease; asthma requiring more than as needed bronchodilators for management; or other autoimmune lung disease
  7. Pregnancy (urine hCG)
  8. Breast feeding
  9. History of autoimmune disease
  10. Involved in other experimental protocols (except with permission of the other study PI)

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • Female or male
  • Menopausal status not specified
  • Immunologically intact by recall anergy testing
  • Negative pregnancy test

Exclusion criteria:

  • Karnofsky 0-60% or ECOG ≥ 2
  • Total bilirubin > 1.8 g/dL
  • Creatinine > 2.0 g/dL
  • Hemoglobin < 10.0 g/dL
  • Platelet count < 50,000/mm³
  • WBC< 2,000/mm³
  • Active pulmonary disease requiring medication that includes multiple inhalers
  • Pregnancy
  • Breastfeeding
  • History of autoimmune disease

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

  • See Disease Characteristics

Exclusion criteria:

  • Concurrent immunosuppressive therapy including chemotherapy, steroids, or methotrexate
  • Concurrent participation in another experimental treatment (except with permission of the other study investigator)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Germany,   Greece
 
NCT00524277
CDR0000562261, BAMC-C.2007.098, WRNMMC-20225
Yes
COL George Peoples, MD, FACS, San Antonio Military Medical Center
San Antonio Military Medical Center
  • Antigen Express, Inc.
  • Norwell, Inc.
Principal Investigator: Elizabeth A Mittendorf, MD, FACS UT M.D. Anderson Cancer Center
Study Director: George E Peoples, MD, FACS Cancer Vaccine Development Program, Department of Surgery, Brooke Army Medical Center
San Antonio Military Medical Center
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP