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)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 3
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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:
- •18 and over
- •Menopausal status
- •Not specified
- •Performance status
- •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
- •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
- •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
- •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
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排除标准
- 未提供