Vaccine Therapy in Treating Patients With HER2/Neu Positive or Negative Stage IV Breast Cancer or Other HER2/Neu Positive Cancers

Study Overview
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Brief Summary
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RATIONALE: Vaccines made from gene-modified tumor cells may make the body build an immune response to kill tumor cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Interferon alfa may interfere with the growth of tumor cells. Combining vaccine therapy with cyclophosphamide and interferon alfa may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining vaccine therapy with interferon alfa and cyclophosphamide in treating patients who have stage IV breast cancer.

Detailed Description
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OBJECTIVES: Determine the safety, tolerability, and feasibility of vaccine therapy comprising an allogeneic (non-self) tumor cell line transfected with the sargramostim (GM-CSF) gene combined with low-dose interferon alfa and low-dose cyclophosphamide in patients with stage IV breast cancer or other solid tumors. Determine the clinical response, time to progression, and survival of patients treated with this regimen. Correlate clinical response with immunological response in patients treated with this regimen. OUTLINE: Patients receive low-dose cyclophosphamide IV once 2-3 days before each tumor vaccine. Patients then receive tumor vaccine comprising HER2/neu-positive allogeneic (non-self) breast cancer cells transfected with the sargramostim (GM-CSF) gene intradermally (ID) on day 1. Patients also receive low-dose interferon alfa ID approximately 48 and 96 hours after each tumor vaccine. Treatment repeats every 2 weeks for 3 vaccinations and then monthly for 3 vaccinations in the absence of disease progression or unacceptable toxicity. Patients are followed at 2 weeks and then every 3 months thereafter. PROJECTED ACCRUAL: A total of 9-24 patients will be accrued for this study.

Official Title
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A Phase 1-2 Study for Stage IV Breast and HER2/Neu Positive Cancers to Evaluate the Safety and Efficacy of a Vaccine Using Whole Cells From the SVBR- 1-GM Cell Line Genetically Engineered To Produce Granulocyte- Macrophage Colony Stimulating Factor

Conditions
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Breast Cancer, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Biological: allogeneic GM-CSF-secreting breast cancer vaccine
* Biological: recombinant interferon alfa
* Drug: cyclophosphamide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed breast cancer meeting 1 of the following criteria: Recurrent and/or metastatic lesions that are HER2/neu-positive or negative Recurrent or progressive cancer of the lung, ovary, pancreas, prostate, bladder, or other primary site associated with HER2/neu-positive tumor by histochemistry Bone-only metastatic breast cancer, cytologically confirmed malignant effusions, histologically confirmed marrow involvement, or other evaluable (but non-measurable) metastatic disease allowed Failed prior first-line chemotherapy (e.g., anthracycline- or taxane-based therapy) with or without adjuvant chemotherapy or hormonal therapy No curative or reliably effective palliative surgery, radiotherapy, or medical therapy available Stable brain metastases allowed provided the following criteria are met*: Previously treated No concurrent requirement for corticosteroids No radiological or clinical deterioration within the past 6 weeks NOTE: *Patients who had recent treatment with gamma knife or intensity-modulated radiotherapy for brain metastases are eligible provided there has been recovery from known or anticipated toxic effects Patients with no HLA-A2 allele are eligible Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age 18 and over Sex Female or male Menopausal status Not specified Performance status ECOG 0-2 Life expectancy At least 4 months Hematopoietic Absolute granulocyte count ≥ 1,000/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Bilirubin ≤ 2 mg/dL Alkaline phosphatase ≤ 5 times upper limit of normal (ULN) ALT and AST ≤ 2 times ULN Renal BUN ≤ 30 mg/dL Creatinine ≤ 2 mg/dL ≤ 1 g protein on 24-hour urine collection OR ≤ 1+ proteinuria on urinalysis Cardiovascular Hypertension controlled by agents (except beta-blockers) allowed Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception HIV negative No history of anaphylactic reaction to any known or unknown antigen No history of clinical hypersensitivity to sargramostim (GM-CSF), interferon, yeast, beef, or to any components used in preparation of study vaccine No clinical or laboratory features indicative of AIDS No rheumatological, psychiatric, or other clinically progressive major medical problems requiring treatment No other malignancy within the past 2 years PRIOR CONCURRENT THERAPY: Biologic therapy More than 3 weeks since prior biological therapy, including trastuzumab (Herceptin^®) More than 3 weeks since prior immunotherapy No concurrent immunotherapy Chemotherapy See Disease Characteristics More than 3 weeks since prior chemotherapy (8 weeks for nitrosoureas or mitomycin) No concurrent chemotherapy Endocrine therapy See Disease Characteristics More than 3 weeks since prior hormonal therapy No concurrent hormonal therapy No concurrent systemic steroids Concurrent inhalation steroids for respiratory hypersensitivity (e.g., triamcinolone nasal or pulmonary inhalers) allowed Radiotherapy See Disease Characteristics More than 3 weeks since prior radiotherapy No concurrent radiotherapy Surgery More than 3 weeks since prior major surgery with general anesthesia No concurrent major surgery Other Recovered from prior therapy Patients receiving pamidronate, bisphosphonates, or other supportive measures must continue therapy during study participation No concurrent anticoagulants No concurrent beta-blockers for control of mild hypertension or other indications

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: allogeneic GM-CSF-secreting breast cancer vaccine|nan|
|Biological: recombinant interferon alfa|nan|
|Drug: cyclophosphamide|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety, tolerability, and feasibility |  |  | 
| Clinical response |  |  | 
| Time to progression |  |  | 
| Survival |  |  | 
| Correlation of clinical response with immunological response |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent breast cancer, stage IV breast cancer, male breast cancer, unspecified adult solid tumor, protocol specific