Radiolabeled Monoclonal Antibody Therapy Followed by Bone Marrow or Peripheral Stem Cell Transplantation in Treating Patients With Metastatic Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Radiolabeled monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Peripheral stem cell transplantation or bone marrow transplantation may be able to replace immune cells that were destroyed by monoclonal antibody therapy used to kill tumor cells. PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibody therapy followed by bone marrow or peripheral stem cell transplantation in treating patients who have metastatic breast cancer.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of yttrium Y 90 labeled, humanized monoclonal antibody BrE-3 when given in combination with indium In 111 labeled, humanized monoclonal antibody BrE-3 followed by autologous bone marrow or peripheral blood stem cell transplantation in patients with metastatic breast cancer. Determine hematopoietic engraftment in these patients treated with this regimen. Determine the ability of indium In 111 labeled, humanized monoclonal antibody BrE-3 to image metastatic disease in these patients. Determine the pharmacokinetics of this regimen in these patients. Determine the preliminary antitumor response in these patients treated with this regimen. OUTLINE: This is a dose escalation study of yttrium Y 90 labeled, humanized monoclonal antibody BrE-3 (Y90 huMOAB BrE-3). Patients receive Y90 huMOAB BrE-3 and indium In 111 labeled, humanized monoclonal antibody BrE-3 IV over 1-2 hours on day -14. Patients undergo autologous bone marrow or peripheral blood stem cell transplantation on day 0. Patients also receive filgrastim (G-CSF) IV beginning on day 0 and continuing until blood counts recover. Cohorts of 3-6 patients receive escalating doses of Y90 huMOAB BrE-3 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicities. Patients are followed every 3-4 months for 1 year and then at least annually thereafter. PROJECTED ACCRUAL: Approximately 3-30 patients will be accrued for this study.

Official Title
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Phase I Study of 90-Y-Humanized-BrE-3 Followed by Autologous Hematopoietic Progenitor Cell Support in Patients With Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: filgrastim
* Procedure: autologous bone marrow transplantation
* Procedure: peripheral blood stem cell transplantation
* Radiation: indium In 111 monoclonal antibody BrE-3
* Radiation: yttrium Y 90 monoclonal antibody BrE-3


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed metastatic breast cancer BrE-3 positive Relapsed or refractory disease with tumor progression after effective therapy allowed Measurable or evaluable disease Received at least one prior chemotherapy regimen for metastatic disease and have at least one of the following: Chemotherapy refractory liver metastases more than 2 cm Multiple non-resectable liver metastases Brain metastases Prior high-dose chemotherapy Relapse within prior radiotherapy field Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age: Over 18 Sex: Male or female Menopausal status: Not specified Performance status: 0-1 Life expectancy: Not specified Hematopoietic: WBC greater than 3,000/mm3 Absolute neutrophil count greater than 1,000/mm3 Platelet count greater than 100,000/mm3 Hepatic: Bilirubin less than 2 times normal SGOT/SGPT less than 2 times normal Renal: Creatinine clearance greater than 60 mL/min Cardiovascular: LVEF greater than 45% by MUGA scan Pulmonary: DLCO and FEV 1.0 greater than 60% predicted Other: Not pregnant Negative pregnancy test Fertile patients must use effective contraception No known hypersensitivity to E. coli derived proteins No other comorbid condition that would preclude study PRIOR CONCURRENT THERAPY: Biologic therapy: No prior high-dose chemotherapy with autologous peripheral blood stem cell transplantation Chemotherapy: See Disease Characteristics See Biologic therapy Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics Surgery: Not specified Other: Recovered from prior therapy

Ages Eligible for Study
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Minimum Age: 18 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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: filgrastim|nan|
|Procedure: autologous bone marrow transplantation|nan|
|Procedure: peripheral blood stem cell transplantation|nan|
|Radiation: indium In 111 monoclonal antibody BrE-3|nan|
|Radiation: yttrium Y 90 monoclonal antibody BrE-3|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV breast cancer, recurrent breast cancer, male breast cancer