A Phase I, Multi-Dose Study of RAV12 (ANTI-RAAG12 MAB) in Patients With Metastatic or Recurrent Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- MacroGenics
- 入组人数
- 53
- 试验地点
- 5
- 主要终点
- Toxicity by CTCAE
研究概览
简要总结
RATIONALE: Monoclonal antibodies, such as RAV12, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.
PURPOSE: This phase I trial is studying the side effects and best dose of RAV12 in treating patients with metastatic or recurrent adenocarcinoma.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose of RAV12 in patients with metastatic or recurrent adenocarcinoma.
- Determine the toxicity profile of this drug in these patients.
- Determine the pharmacokinetics and immunogenicity of this drug in these patients.
- Determine, preliminarily, the antitumor activity of this drug in these patients.
OUTLINE: This is an open-label, dose-escalation study.
Patients receive RAV12 IV over 2 hours 2-3 times per week in weeks 1-4 (course 1). Patients are evaluated for response on day 43. Patients achieving a partial or complete response may be eligible to receive additional courses of RAV12 as above. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of RAV12 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Up to 15 additional patients are treated at the MTD in 1 or more patients groups (e.g., colorectal, pancreatic, gastroesophageal, and other adenocarcinoma).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed adenocarcinoma
- •Metastatic or recurrent disease
- •Not curable by standard therapies
- •Must have failed at least 1, but no more than 3, prior therapies for metastatic or recurrent disease
- •Patients with colorectal or breast adenocarcinoma must have failed at least 2 prior therapies
- •Must have had at least stable disease for 3 months while on last treatment prior to most recent disease progression
- •Meets 1 of the following criteria:
- •At least 1 measurable site of disease ≥ 2 cm by radiography
- •Evaluable disease that could be reliably and consistently followed, as deemed by the principal investigator
- •RAAG12 expression confirmed* by immunohistochemistry NOTE: *Not required for patients with colon, pancreatic, or gastric adenocarcinoma
- •No evidence of residual or recurrent CNS metastases
- •Hormone receptor status:
- •Not specified
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Not specified
- •Menopausal status
- •Not specified
- •Performance status
- •Life expectancy
- •More than 3 months
- •Hematopoietic
- •Platelet count ≥ 100,000/mm^3
- •Hemoglobin ≥ 9.0 g/dL (transfusions allowed)
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •AST and ALT ≤ 2.5 times ULN
- •Alkaline phosphatase ≤ 2.5 times ULN
- •γ-glutamyl transferase ≤ 2.5 times ULN
- •Adequate hepatic function sufficient to undergo study therapy
- •Creatinine < 1.5 mg/dL
- •Adequate renal function sufficient to undergo study therapy
- •Cardiovascular
- •No New York Heart Association class III or IV heart disease
- •No thrombosis within the past 3 months, including any of the following:
- •Deep vein thrombosis
- •Myocardial infarction
- •Adequate cardiac function sufficient to undergo study therapy
- •No pulmonary embolism within the past 3 months
- •No significant pulmonary compromise, particularly dependence on supplemental oxygen on an as-needed or continuous basis
- •Adequate pulmonary function sufficient to undergo study therapy
- •Immunologic
- •No active viral, bacterial or systemic fungal infection requiring parenteral therapy within the past 4 weeks
- •No history of chronic or recurrent infection requiring continual antiviral, antifungal, or antibacterial agents
- •No known hypersensitivity to murine or recombinant proteins, polysorbate 80, or any excipient contained in study drug
- •Amylase and lipase normal
- •No other primary malignancy within the past 3 years except for the following:
- •Treated non-melanoma skin cancer
- •Carcinoma in situ of the cervix by biopsy
- 另有 30 项未显示
排除标准
- 未提供
研究组 & 干预措施
RAV12
干预措施: monoclonal antibody RAV12 (Biological)
结局指标
主要结局
Toxicity by CTCAE
时间窗: Days 1-50
次要结局
- Maximum tolerated dose(Days 1-50)
- Pharmacokinetics of RAV12 by serum levels(Days 1, 2, 4, 5, 8, 15, 22, 29, 36, 43, and 50)
- Immunogenicity by Human Anti-chimeric antibodies(Days 1, 8, 15, 22, and 50)
- Progression free survival by clinical assessment(3 and 6 months)
- Time to tumor progression by clinical assessment(6 months)