Monoclonal Antibody Therapy in Treating Women With Locally Advanced or Metastatic Breast Cancer Previously Treated With Combination Chemotherapy

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. PURPOSE: Phase I/II trial to study the effect of monoclonal antibody therapy on the body and its effectiveness in treating women who have locally advanced or metastatic breast cancer that was previously treated with combination chemotherapy.

Detailed Description
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OBJECTIVES: Determine the safety and tolerability of monoclonal antibody HuHMFG1 in women with locally advanced or metastatic breast cancer previously treated with anthracycline and taxane-based therapy. Determine the maximum tolerated dose and appropriate schedule of this drug in these patients. Determine the pharmacokinetic profile of this drug in these patients. Determine the tumor response rate, progression-free survival, and median survival of patients treated with this drug. Analyze immunological markers for evaluation of disease status (e.g., in vitro analysis of antibody-dependent cellular cytotoxicity, natural killer cell activity, complement depletion, and tumor markers CA 15.3 and CEA) in patients treated with this drug. OUTLINE: This is a dose-escalation, open-label, nonrandomized, multicenter study. Phase I: Patients receive monoclonal antibody HuHMFG1 IV over 1-3 hours once every 3 weeks for doses 1 and 2. All subsequent dose intervals are based on individual half-life value of the drug. Patients receive at least 6 doses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of monoclonal antibody HuHMFG1 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Phase II:Patients receive monoclonal antibody HuHMFG1 as above at the MTD. Patients are followed at 28 days. PROJECTED ACCRUAL: Approximately 3-40 patients (3-15 patients for phase I and 19-25 patients for phase II) will be accrued for this study within approximately 12 months.

Official Title
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An Open Label Phase I/II Study of Humanized Human Milk Fat Globule-1 (THEREX) in Patients With Locally Advanced or Metastatic Breast Cancer Following Prior Anthracycline and Taxane Therapy

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: monoclonal antibody HuHMFG1


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed breast cancer Locally advanced or metastatic disease No inflammatory breast cancer Polymorphic epithelial mucin (PEM) antigen overexpression by immunohistochemistry Previously treated with an anthracycline and a taxane in any combination for breast cancer No more than 2 prior chemotherapy regimens, including adjuvant /neoadjuvant therapy No more than 1 prior regimen for distant metastatic disease Any number of prior hormonal or biologic therapy regimens allowed Measurable disease At least one unidimensionally measurable lesion not previously irradiated The following are not considered measurable lesions: Bone Leptomeningeal disease Ascites Pleural/pericardial effusion Lymphangitis cutis/pulmonis Abdominal masses not confirmed and followed by imaging techniques Cystic lesions No metastases accessible to complete surgical resection No CNS metastasis by CT scan Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age 18 and over Sex Female Menopausal status Not specified Performance status WHO 0-2 Life expectancy At least 4 months Hematopoietic Hemoglobin at least 10 g/dL 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 ALT and AST no greater than 2.5 times upper limit of normal (ULN) (less than 5 times ULN if liver metastases are present) Renal Creatinine no greater than 1.5 times ULN OR Creatinine clearance greater than 60 mL/min No hyperuricemia (uric acid at least 1.25 times ULN) No hypercalcemia (calcium at least 11.5 mg/dL [corrected for serum albumin]) Cardiovascular LVEF at least 45% by MUGA or echocardiogram within the past 4 weeks Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3-6 months after study participation No other prior malignancy within the past 5 years except adequately treated nonmelanoma skin cancer or cervical intraepithelial neoplasia No other concurrent uncontrolled comorbid illness that represents unacceptable risk in the opinion of the investigator No legal incapacity PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics More than 2 weeks since prior growth factors to aid hematologic recovery No other concurrent immunotherapy Chemotherapy See Disease Characteristics More than 4 weeks since prior cytotoxic chemotherapy No concurrent chemotherapy for metastatic breast cancer Endocrine therapy See Disease Characteristics No concurrent endocrine therapy for metastatic breast cancer No concurrent chronic corticosteroid therapy No concurrent high-dose corticosteroids Radiotherapy More than 4 weeks since prior radiotherapy except for palliation No concurrent antitumor radiotherapy except for palliation Surgery More than 4 weeks since prior major surgery Other More than 2 weeks since prior blood transfusions to aid hematologic recovery No participation in any other investigational drug study No other concurrent investigational drugs No other concurrent antitumor therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: monoclonal antibody HuHMFG1|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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recurrent breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer