Vaccine Therapy in Treating Patients With Breast Cancer

San Antonio Military Medical Center

Status and phase: Completed; Phase 2

Conditions: Breast Cancer

Treatments: Biological: AE37 + GM-CSF vaccine; Biological: GM-CSF (sargramostim); Biological: GP2 peptide + GM-CSF vaccine

Study type: Interventional

Funder types: Other U.S. Federal agency; Industry

Identifiers

NCT00524277

WRNMMC-20225 (Other Identifier)

CDR0000562261

BAMC-C.2007.098 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 456 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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)

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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456 participants in 4 patient groups

Arm I

Experimental group

Description:

HLA-A2-positive patients receive GP2 peptide + GM-CSF vaccine intradermally (ID) every 3-4 weeks for a total of up to 6 inoculations.

Treatment:

Biological: GP2 peptide + GM-CSF vaccine

Arm II

Active Comparator group

Description:

HLA-A2-positive patients receive GM-CSF ID every 3-4 weeks for a total of up to 6 inoculations.

Treatment:

Biological: GM-CSF (sargramostim)

Biological: GM-CSF (sargramostim)

Arm III

Experimental group

Description:

HLA-A2-negative patients receive AE37 peptide/GM-CSF vaccine ID every 3-4 weeks for a total of up to 6 inoculations.

Treatment:

Biological: AE37 + GM-CSF vaccine

Arm IV

Active Comparator group

Description:

HLA-A2-negative patients receive GM-CSF ID ID every 3-4 weeks for a total of up to 6 inoculations

Treatment:

Biological: GM-CSF (sargramostim)

Biological: GM-CSF (sargramostim)