RATIONALE: Chemotherapy uses different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. PURPOSE: Phase I/II trial to study the effectiveness of chemotherapy and peripheral stem cell transplantation followed by trastuzumab in treating women who have metastatic breast cancer.

Condition	Treatment or Intervention	Phase
stage IV breast cancer	Procedure: chemotherapy  Procedure: biological response modifier therapy  Procedure: monoclonal antibody therapy  Procedure: peripheral blood stem cell transplantation  Procedure: antibody therapy  Drug: bone marrow ablation with stem cell support  Drug: carboplatin  Drug: carmustine  Drug: cisplatin  Drug: cyclophosphamide  Drug: thiotepa  Drug: trastuzumab	Phase I Phase II

Further Study Details: 

OBJECTIVES: I. Determine the safety and toxicity profile, specifically cardiac toxicity, of trastuzumab (Herceptin) following high dose chemotherapy and autologous peripheral blood stem cell transplantation in women with metastatic breast cancer. II. Determine the time to disease progression and disease free survival in these patients when treated with this regimen. III. Determine the impact of trastuzumab (Herceptin) on minimal residual disease after autologous peripheral blood stem cell transplantation as evidenced by serial immunocytochemical analysis of bone marrow. IV. Determine the relationship between posttransplant reconstitution of antibody dependent cellular toxicity and the efficacy of trastuzumab (Herceptin) in these patients.

PROTOCOL OUTLINE: This is a multicenter study. Patients undergo stem cell mobilization with growth factors alone (filgrastim (G-CSF) and/or sargramostim (GM-CSF)) or chemotherapy followed by growth factors (depending on center). Peripheral blood stem cells (PBSC) are then collected by leukapheresis. Patients then receive high dose chemotherapy consisting of cyclophosphamide IV over 1 hour and cisplatin IV over 72 hours on days -6 to -4 and carmustine IV on day -3 or cyclophosphamide IV, thiotepa IV, and carboplatin IV over 96 hours on days -7 to -4 (depending on center). PBSC are reinfused on day 0. Patients then receive trastuzumab IV over 30-90 minutes weekly for 1 year or until disease progression beginning 5-8 weeks after PBSC reinfusion.

PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study.

Ages Eligible for Study:  18 Years   -   65 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed stage IV breast cancer that overexpresses HER2/neu
• Evidence of at least a partial response (at least 50% reduction) to salvage chemotherapy as initial chemotherapy for metastatic disease
• Measurable disease not required if there is no disease progression at induction chemotherapy
• Bone lesions as only site of metastatic disease allowed if evidence of clinical improvement and no new lesions on x-ray
• No CNS metastases
• Hormone receptor status: Not specified

--Prior/Concurrent Therapy--

• Biologic therapy: Prior trastuzumab allowed; No prior bone marrow or peripheral blood stem cell transplantation
• Chemotherapy: See Disease Characteristics; Prior doxorubicin not to exceed total cumulative dose of 360 mg/m2; No more than 6 standard courses of pretransplant salvage chemotherapy; No more than 3 months of prior weekly taxane therapy; More than 1 chemotherapy regimen allowed with no progression during chemotherapy
• Endocrine therapy: Concurrent tamoxifen therapy allowed for estrogen receptor positive patients who have not received prior hormonal therapy; No other concurrent hormonal therapy
• Radiotherapy: No concurrent radiotherapy
• Surgery: Not specified
• Other: Concurrent pamidronate allowed for bone lesions

--Patient Characteristics--

• Age: 18 to physiologic 65
• Sex: Female
• Menopausal status: Pre or postmenopausal
• Performance status: Karnofsky 80-100%
• Life expectancy: At least 6 months
• Hematopoietic: WBC at least 2,500/mm3; Absolute neutrophil count at least 1,000/mm3; Platelet count at least 100,000/mm3
• Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN); SGOT no greater than 2.5 times ULN
• Renal: Creatinine no greater than 2.0 mg/dL
• Cardiovascular: LVEF at least 45% by radionucleotide ventriculogram; No uncontrolled hypertension; No unstable angina; No New York Heart Association class IV heart disease or congestive heart failure; No coronary angioplasty or myocardial infarction within past 6 months; No uncontrolled atrial or ventricular cardiac arrhythmias
• Pulmonary: FEV1 and DLCO at least 50%
• Other: Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception; HIV negative; No insulin dependent diabetes mellitus; No uncontrolled active systemic infection; No other significant nonmalignant disease; No other malignancy in past 5 years except surgically cured nonmelanoma skin cancer or carcinoma in situ of the cervix

Massachusetts
      Beth Israel Deaconess Medical Center, Boston,  Massachusetts,  02215,  United States
New Jersey
      Hackensack University Medical Center, Hackensack,  New Jersey,  07601,  United States

Study chairs or principal investigators

David Avigan,  Study Chair,  Beth Israel Deaconess Medical Center   

Study ID Numbers:  CDR0000068138; BIH-99-12; NCI-V00-1610; BIH-W-99-0053-FB
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  August 3, 2000
ClinicalTrials.gov Identifier:  NCT00006123
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08