HER-2 Protein Vaccine in Treating Women With Breast Cancer

A Phase I Trial Evaluating The Safety Of Intramuscular Injections Of HER-2 Protein AUTOVAC (PX104.1.6) In Patients With Breast Cancer

RATIONALE: Vaccines may make the body build an immune response to kill tumor cells.

PURPOSE: Phase I trial to study the effectiveness of HER-2 protein vaccine in treating women who have breast cancer.

OBJECTIVES:

Primary

• Determine the safety of HER-2 protein AutoVac™ in women with breast cancer.

Secondary

• Determine the ability of this drug to bypass the tolerance to the HER-2 self-protein by raising HER-2 antibodies in these patients.
• Determine the kinetics of the immune response to HER-2/neu in patients treated with this drug.

OUTLINE: This is an open-label, multicenter study.

Patients receive HER-2 protein AutoVac™ intramuscularly at weeks 0, 2, 6, and 10 in the absence of unacceptable toxicity.

Patients are followed for up to 6 weeks.

PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study within 3 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the breast, meeting criteria for 1 of the following:

  • Metastatic disease currently in complete or partial response or stable disease

    • Have been receiving a stable endocrine therapy regimen (e.g., aromatase inhibitor, tamoxifen, fulvestrant, or gonadotropin-releasing hormone agonist) for at least 30 days OR status post oophorectomy

  • Completed a course of local and adjuvant systemic therapy for high-risk stage II or III disease (i.e., anticipated 5-year relative survival is no greater than 50%) meeting any of the following staging criteria:

    • Stage IIB with involvement of at least 4 nodes
    • Stage IIIA (T3 disease with involvement of at least 4 nodes)
    • Any stage IIIB or IIIC disease

  • Stage IV with no evidence of disease (e.g., prior resection of local chest wall recurrence with no evidence of disease elsewhere)

• 1+, 2+, or 3+ HER2/neu expression by immunohistochemistry

• Treatment with trastuzumab (Herceptin®) not clinically indicated

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Female

Menopausal status

• Not specified

Performance status

• ECOG 0-1

Life expectancy

• At least 6 months

Hematopoietic

• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10 g/dL
• Absolute neutrophil count at least 1,500/mm^3

Hepatic

• ALT or AST no greater than 2.5 times upper limit of normal (ULN) (5 times ULN for patients with liver metastases)
• Bilirubin no greater than 2 mg/dL (unless due to Gilbert's disease)

Renal

• Creatinine no greater than 2 mg/dL

Cardiovascular

• No history of significant cardiovascular disease
• No myocardial infarction within the past 6 months
• No poorly controlled cardiac arrhythmia
• No New York Heart Association class III or IV heart disease
• LVEF at least 50% by MUGA

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy except basal cell skin cancer or adequately treated carcinoma in situ of the cervix
• No concurrent severe autoimmune disease
• No other clinically significant or serious medical disease that would preclude study participation or compromise patient safety or the results of this study

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 4 months since prior trastuzumab
• No prior anticancer vaccine therapy
• No concurrent trastuzumab
• No concurrent immunomodulators (e.g., thalidomide or interferons/interleukins)

Chemotherapy

• More than 4 weeks since prior chemotherapy
• No concurrent low-dose methotrexate or cyclophosphamide
• No concurrent cytotoxic chemotherapy

Endocrine therapy

• See Disease Characteristics

• No concurrent corticosteroids

  • Topical or inhaled steroids are allowed

• No changes to current endocrine therapy regimen (e.g., discontinuation or addition of an agent)

Radiotherapy

• More than 3 months since prior radiotherapy involving more than 25% of the bone marrow
• No concurrent radiotherapy

Surgery

• See Disease Characteristics
• No prior bilateral breast procedures

Other

• More than 4 weeks since prior immunosuppressive therapy
• More than 30 days since prior investigational agents or clinical trial participation
• No other concurrent experimental or investigational agents
• No concurrent cyclosporine
• No concurrent immunosuppressive agents