Monoclonal Antibody Therapy, Cyclosporine, and Paclitaxel in Treating Patients With Recurrent or Refractory Metastatic Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining monoclonal antibody therapy with cyclosporine and paclitaxel may be an effective treatment for metastatic breast cancer. PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibody therapy, cyclosporine, and paclitaxel in treating patients who have recurrent or refractory metastatic breast cancer.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of yttrium Y 90 monoclonal antibody m170 in combination with cyclosporine and paclitaxel in patients with recurrent or refractory metastatic breast cancer. Determine the preliminary efficacy of this regimen in these patients. OUTLINE: This is a dose-escalation study of yttrium Y 90 monoclonal antibody m170 (Y90 MOAB m170). Patients receive filgrastim (G-CSF) subcutaneously (SC) daily for 4 days prior to apheresis which continues daily for a maximum of 5 days. A minimum of 6 million CD34+ cells/kg must be harvested. Patients receive oral cyclosporine every 12 hours on days -3 to 25. Patients receive unlabeled monoclonal antibody (MOAB) m170 IV followed by a tracer dose of indium In 111 MOAB m170 IV on day 0. On day 7, patients receive unlabeled MOAB m170 IV followed by Y90 MOAB m170 IV. Patients in cohorts 2-4 also receive paclitaxel IV over 3 hours on day 9. If needed, patients undergo autologous peripheral blood stem cell transplantation on day 21 and receive G-CSF SC daily until blood counts recover. Cohorts of 3-6 patients receive escalating doses of Y90 MOAB m170 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 toxicity. Patients are followed monthly for 3 months, every 3 months for 1 year, and then every 6 months for 1 year. PROJECTED ACCRUAL: A total of 18-30 patients will be accrued for this study within 36 months.

Official Title
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Combined Modality Radioimmunotherapy For Metastatic Breast Adenocarcinoma With Two Cycles Of Escalating Dose 90Y-DOTA-peptide-m170 and Fixed, Low Dose Paclitaxel With Blood Stem Cell Support And Cyclosporin For HAMA Suppression

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: filgrastim
* Biological: monoclonal antibody m170
* Drug: cyclosporine
* Drug: paclitaxel
* Procedure: peripheral blood stem cell transplantation
* Radiation: yttrium Y 90 monoclonal antibody m170


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed metastatic breast adenocarcinoma Residual or recurrent disease after first-line standard chemotherapy Clinical evidence of metastatic disease Tumor cells positive for m170 immunoreactivity HAMA titer negative Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age: 18 and over Sex: Not specified Menopausal status: Not specified Performance status: Karnofsky 70-100% Life expectancy: Not specified Hematopoietic: Neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than 1.5 mg/dL Renal: Creatinine less than 1.5 mg/dL Cardiovascular: LVEF at least 50% by MUGA Pulmonary: FEV1 at least 65% of predicted FVC at least 65% of predicted DLCO at least 60% Other: No other malignancy within the past 5 years except nonmelanoma skin cancer or adequately treated carcinoma in situ of the cervix Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: See Chemotherapy Chemotherapy: See Disease Characteristics At least 1 prior chemotherapy regimen for advanced disease Prior high-dose chemotherapy with autologous stem cell transplantation is allowed if given at least 12 months prior to study and carmustine was not used At least 4 weeks since prior chemotherapy Endocrine therapy: Not specified Radiotherapy: At least 4 weeks since prior external beam radiotherapy No prior radiotherapy to more than 25% of the total skeleton Surgery: Not specified Other: No requirement for oral anticoagulants (low-dose warfarin for central line thrombosis prophylaxis allowed)

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|
|Biological: monoclonal antibody m170|nan|
|Drug: cyclosporine|nan|
|Drug: paclitaxel|nan|
|Procedure: peripheral blood stem cell transplantation|nan|
|Radiation: yttrium Y 90 monoclonal antibody m170|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