Breast Cancer Clinical Trial
Vaccine Therapy With or Without Cyclophosphamide and Doxorubicin in Women With Stage IV Breast Cancer
Summary
RATIONALE: Vaccines made from a person's tumor cells may make the body build an immune response to kill tumor cells. Drugs used in chemotherapy, such as cyclophosphamide and doxorubicin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining vaccine therapy with cyclophosphamide and doxorubicin may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of cyclophosphamide and doxorubicin when given with vaccine therapy in treating women with stage IV breast cancer.
Full Description
OBJECTIVES:
Primary
Determine the safety of vaccination comprising allogeneic sargramostim (GM-CSF)-secreting breast cancer cells with or without immunomodulation using cyclophosphamide and doxorubicin in women with stage IV breast cancer.
Determine the doses of cyclophosphamide and doxorubicin that maximize vaccine-induced immunity, in terms of immune response to HER2/neu, in patients treated with these regimens.
Compare in vivo immune response induced by these regimens, as measured by immunohistochemical analysis of vaccine site biopsies from these patients, with responses seen in prior preclinical and clinical studies.
Secondary
Determine the time to disease progression in patients treated with these regimens.
OUTLINE: This is a dose-finding study.
The first 6 patients receive 1 of 2 doses of vaccine comprising allogeneic sargramostim (GM-CSF)-secreting breast cancer cells intradermally (ID) on day 0. Subsequent patients receive cyclophosphamide IV on day -1, vaccine at the higher dose ID on day 0, and doxorubicin IV on day 7. Treatment in all patients repeats every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease after the third course receive a fourth course of treatment at approximately 4 months after completion of the third course.
Cohorts of 2-3 patients receive a fixed dose of vaccine in combination with escalating doses of doxorubicin and cyclophosphamide. Doses of cyclophosphamide and doxorubicin are escalated until an optimal dose of combination chemotherapy with a fixed dose of vaccine is achieved.
Patients are followed at 1 month and 4 months after completion of study therapy and then annually thereafter.
PROJECTED ACCRUAL: A total of 6-60 patients will be accrued for this study.
Eligibility Criteria
DISEASE CHARACTERISTICS:
Histologically confirmed adenocarcinoma of the breast
Stage IV disease
Stable disease for ≥ 28 days
Measurable or evaluable disease OR no evidence of disease
Not eligible for potentially curative therapy
Adequately treated CNS metastases are allowed
Hormone receptor status:
Not specified
HER-2/neu status:
Not specified
PATIENT CHARACTERISTICS:
Age
18 and over
Sex
Female
Menopausal status
Not specified
Performance status
ECOG 0-1
Life expectancy
Not specified
Hematopoietic
Absolute neutrophil count > 1,000/mm^3
Platelet count > 100,000/mm^3
Hepatic
Bilirubin ≤ 2.0 mg/dL (unless due to Gilbert's syndrome)
AST and ALT ≤ 2 times upper limit of normal (ULN)
Alkaline phosphatase ≤ 5 times ULN
Renal
Creatinine < 2.0 mg/dL
Cardiovascular
Ejection fraction ≥ 45% by echocardiogram or MUGA
Pulmonary
Asthma or chronic obstructive pulmonary disease allowed provided daily systemic corticosteroid therapy is not required
Immunologic
No active autoimmune disease requiring systemic immunosuppressive therapy, including any of the following:
Inflammatory bowel disease
Systemic vasculitis
Scleroderma
Psoriasis
Multiple sclerosis
Hemolytic anemia
Immune-mediated thrombocytopenia
Rheumatoid arthritis
Systemic lupus erythematosus
Sjögren's syndrome
Sarcoidosis
Other rheumatologic disease
HIV negative
No active acute or chronic infection
No allergy to corn
Other
No other malignancy within the past 5 years except carcinoma in situ of the cervix, superficial nonmelanoma skin cancer, or superficial bladder cancer
No active major medical or psychosocial problem that would preclude study participation
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
More than 28 days since prior biologic therapy
No other concurrent biologic therapy, including trastuzumab (Herceptin®)
Chemotherapy
Prior adjuvant chemotherapy allowed
Prior doxorubicin and cyclophosphamide allowed
Prior doxorubicin dose combined with planned study therapy dose must not exceed a lifetime cumulative dose of ≥ 450 mg/m^2
More than 28 days since prior systemic chemotherapy
No other concurrent systemic chemotherapy
Endocrine therapy
More than 28 days since prior systemic corticosteroids
Concurrent hormonal or endocrine therapy allowed
No concurrent systemic corticosteroids
Radiotherapy
More than 28 days since prior radiotherapy
No concurrent radiotherapy
Surgery
Not specified
Other
More than 28 days since prior participation in another investigational drug trial
No other concurrent investigational drugs
Concurrent bisphosphonates allowed
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There is 1 Location for this study
Baltimore Maryland, 21231, United States
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