Monoclonal Antibody HuHMFG1 in Treating Women With Locally Advanced or Metastatic Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies such as HuHMFG1 can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. PURPOSE: This phase I trial is studying the side effects and best dose of monoclonal antibody HuHMFG1 in treating women with locally advanced or metastatic breast cancer.

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. Determine a safe recommended dose and schedule of this drug in these patients. Determine the pharmacokinetic profile, in the absence of any other chemotherapy or endocrine agent, of this drug in these patients. Determine the antitumor activity of this drug in these patients. Determine time to progression in patients treated with this drug. Assess immunological markers (e.g., granzyme B, gamma interferon, and C1Q) for determining response to this drug in these patients. Assess markers of immunogenicity (e.g., human anti-human antibody) of this drug in these patients. Assess tumor markers (e.g., CA15.3 and CEA) in patients treated with this drug. Correlate, preliminarily, soluble HMFG1 antigen levels with pharmacokinetic data for this drug in these patients. OUTLINE: This is an open-label, non-randomized, dose-escalation study. Patients in cohorts 1 and 2 receive monoclonal antibody HuHMFG1 IV over 1-3 hours once every 21 days for doses 1 and 2. All subsequent dose intervals are based on individual half-life value of the drug, to be within 3 days of the estimated half-life in multiples of 7 days. Patients in cohorts 3 and 4 receive monoclonal antibody HuHMFG1 at the dosing interval determined in the first 2 cohorts. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 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 6 patients experience dose-limiting toxicity. All patients are followed at 4 weeks and then every 6 weeks for 6 months. Patients with an antitumor response or stable disease are followed every 12 weeks until disease progression or initiation of another antitumor treatment. PROJECTED ACCRUAL: A total of 6-24 patients will be accrued for this study within 18 months.

Official Title
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An Open Label Phase I Study of Humanized Human Milk Fat Globule-1 (huHMFG1) Antibody in Patients With Locally Advanced or Metastatic Breast Cancer (TOPCAT)

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 Measurable (RECIST) or evaluable disease (e.g., cytologically or radiologically detectable disease that does not fulfill RECIST criteria) Failed prior OR not a candidate for OR refused anthracycline- and taxane-containing chemotherapy Patients whose tumor overexpresses HER-2 must have failed prior trastuzumab (Herceptin®) No known CNS metastases No metastases accessible to complete surgical resection Unstained slides cut from formalin-fixed and paraffin-embedded tumor blocks available Appropriate tumor block also acceptable Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age 18 and over Sex Female Menopausal status Not specified Performance status WHO 0-1 Life expectancy At least 4 months Hematopoietic Hemoglobin ≥ 10 g/dL Absolute neutrophil count ≥ 1,500/mm^3 WBC ≥ 1,000/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Bilirubin ≤ 1.5 mg/dL ALT or AST ≤ 2.5 times upper limit of normal (ULN) (< 5 times ULN in patients with liver metastases) OR Alkaline phosphatase ≤ 2.5 times ULN (< 5 times ULN in patients with liver metastases) Any degree of elevated alkaline phosphatase allowed provided it is due to bone metastases Renal Creatinine ≤ 1.5 times ULN OR Creatinine clearance > 60 mL/min Uric acid < 1.25 times ULN (for patients with hyperuricemia only) Calcium (corrected for serum albumin) < 11.5 mg/dL (for patients with hypercalcemia only) Cardiovascular LVEF ≥ 45% by MUGA or echocardiogram within the past 4 weeks Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception No other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer or cervical intra-epithelial neoplasia No other uncontrolled illness that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics Prior biological therapy allowed More than 2 weeks since prior blood transfusions or growth factors to aid hematological recovery No other concurrent antitumor immunotherapy Chemotherapy See Disease Characteristics More than 4 weeks since prior cytotoxic chemotherapy No more than 3 prior chemotherapy regimens, including adjuvant/neoadjuvant therapy No concurrent antitumor chemotherapy Endocrine therapy Prior hormonal therapy allowed No concurrent corticosteroids except as physiologic replacement and/or for acute short-term treatment of, or prophylaxis against, infusion reactions No concurrent antitumor hormonal therapy Radiotherapy See Disease Characteristics More than 4 weeks since prior radiotherapy (except for palliative radiotherapy) No concurrent antitumor radiotherapy, except for palliation to non-study lesions Irradiated area should be as small as possible and involve ≤ 10% of the bone marrow in any given 4-week period Surgery More than 4 weeks since prior major surgery Other More than 30 days since prior investigational agents No other concurrent investigational agents

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