Breast Cancer Clinical Trial
Cyclophosphamide and Vaccine Therapy With or Without Trastuzumab in Treating Patients With Metastatic Breast Cancer
Summary
RATIONALE: Vaccines made from gene-modified tumor cells may help the body build an effective immune response to kill tumor cells. Biological therapies, such as cyclophosphamide and trastuzumab, may increase the number of immune cells and make the immune response stronger. It is not yet known whether giving cyclophosphamide together with vaccine therapy is more effective with or without trastuzumab in treating patients with metastatic breast cancer.
PURPOSE: This randomized phase II trial is studying the side effects of giving cyclophosphamide together with vaccine therapy and to see how well it works compared with giving cyclophosphamide and vaccine therapy together with trastuzumab in treating patients with metastatic breast cancer.
Full Description
OBJECTIVES:
Primary
To evaluate the safety of cyclophosphamide-modulated vaccination with vs without trastuzumab in patients with breast cancer that does not overexpress HER-2/neu.
To compare the clinical benefit of cyclophosphamide-modulated vaccination with vs without trastuzumab in these patients.
To measure HER-2/neu-specific CD4+ and CD8+ T-cell immunity by delayed-type hypersensitivity (DTH) and ELISPOT.
To measure the pharmacodynamics of CD4+CD25+ regulatory T cells by flow cytometry.
Secondary
To assess the impact of trastuzumab on immune priming in vivo by immunohistochemistry of vaccine-site biopsies at day +3 and day +7 of courses 1 and 3 on the two study arms, comparing cellular infiltrates to those seen in previous preclinical and clinical models.
To measure hTERT-specific CD8+ T-cell immunity by ELISPOT.
To characterize the peripheral-memory T-cell pool.
Tertiary
To determine baseline and change in vaccine site-draining lymph node immunohistology and gene expression profile.
To develop the tandem tetramer/CD107a cytotoxicity assay for HER-2/neu-specific CD8+ T cells.
To measure novel T-cell responses induced by trastuzumab and cyclophosphamide-modulated vaccination.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic GM-CSF-secreting breast cancer vaccine intradermally on day 0. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months.
Arm II: Patients receive cyclophosphamide and the vaccine as in arm I and trastuzumab IV over 30-90 minutes on day -1. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months.
Skin punch and lymph node biopsies are collected at baseline and on days +3 and +7 of courses 1 and 3 for biomarker analysis.
After completion of study treatment, patients are followed periodically.
Eligibility Criteria
DISEASE CHARACTERISTICS:
Histologically confirmed adenocarcinoma of the breast
Does not overexpress HER-2/neu, defined as FISH negative or 0, 1+, or 2+ by IHC
Stage IV disease
Must not be eligible for therapy of known curative potential for metastatic breast cancer
Measurable or evaluable disease
Stable CNS disease allowed provided that it's adequately treated and not under active treatment
Hormone receptor status not specified
PATIENT CHARACTERISTICS:
Menopausal status not specified
ECOG performance status 0-1
ANC > 1,000/mm^3
Platelets > 100,000/mm^3
Serum bilirubin < 2.0 mg/dL (unless due to Gilbert syndrome)
AST and ALT < 2 times upper limit of normal (ULN)
Alkaline phosphatase < 5 times ULN
Serum creatinine < 2.0 mg/dL
Ejection fraction normal by MUGA OR ≥ 50% by echocardiogram
Not pregnant or nursing
Fertile patients must use effective contraception
HIV negative
Asthma or chronic obstructive pulmonary disease that does not require daily systemic corticosteroids allowed
No prior or concurrent autoimmune disease requiring management with systemic immunosuppression, including any of the following:
Inflammatory bowel disease
Systemic vasculitis
Scleroderma
Psoriasis
Multiple sclerosis
Hemolytic anemia or immune-mediated thrombocytopenia
Rheumatoid arthritis
Systemic lupus erythematosus
Sjogren syndrome
Sarcoidosis
Other rheumatologic disease
No other malignancies within the past 5 years, except carcinoma in situ of the cervix, superficial nonmelanoma skin cancer, superficial bladder cancer, or tamoxifen-related endometrial cancer that has been adequately treated
No active major medical or psychosocial problems that could be complicated by study participation
No symptomatic intrinsic lung disease or extensive tumor involvement of the lungs resulting in dyspnea at rest
No uncontrolled medical problems
No evidence of active acute or chronic infection
No known severe hypersensitivity to trastuzumab, except mild to moderate infusion reactions that are easily managed and do not recur
No allergy to corn
PRIOR CONCURRENT THERAPY:
See Disease Characteristics
More than 28 days since prior and no other concurrent chemotherapy, radiation therapy, or biologic therapy (except trastuzumab)
Concurrent endocrine therapy and supportive therapy with bisphosphonates allowed
More than 28 days since prior and no other concurrent participation in an investigational new drug trial
More than 28 days since prior and no other concurrent systemic oral steroids
Topical, ocular, and nasal steroids allowed
No prior vaccination with the allogeneic GM-CSF-secreting breast tumor vaccine
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There is 1 Location for this study
Baltimore Maryland, 21231, United States
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