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.

Condition	Treatment or Intervention	Phase
stage IV breast cancer recurrent breast cancer	Drug: allogeneic GM-CSF-secreting breast cancer vaccine  Drug: cyclophosphamide  Drug: doxorubicin  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: non-specific immune-modulator therapy  Procedure: tumor cell derivative vaccine  Procedure: vaccine therapy	Phase I

Further Study Details: 

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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
• No CNS metastases
• 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 more than 2 prior chemotherapy regimens for metastatic breast cancer
• 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

Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231-2410,  United States; Recruiting

Study chairs or principal investigators

Leisha A. Emens, MD, PhD,  Principal Investigator,  Sidney Kimmel Cancer Center   

Study ID Numbers:  CDR0000391826; JHOC-J0085; JHOC-RPN-01012502; JHOC-RAC-0304-578; NCT00093834
Record last reviewed:  December 2004
Last Updated:  February 24, 2005
Record first received:  October 6, 2004
ClinicalTrials.gov Identifier:  NCT00093834
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08