A Phase I Study of Yttrium-90 Labeled Humanized Anti-CEA M5A Antibody in Patients With CEA Producing Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 2
- 主要终点
- Overall survival
研究概览
简要总结
RATIONALE: Radiolabeled monoclonal antibodies, such as yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A, can find tumor cells and carry tumor-killing substances to them without harming normal cells. This may be an effective treatment for advanced cancer.
PURPOSE: This phase I trial is studying the side effects and best dose of yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A in treating patients with advanced solid tumors.
详细描述
OBJECTIVES:
- To establish the maximum tolerated dose of yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A and describe the toxicities at each dose studied.
- To estimate radiation doses to whole body, normal organs, and tumor through serial nuclear imaging studies after intravenous infusion of the yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A.
OUTLINE: This is a dose-escalation study of yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A (MOAB M5A).
- Biodistribution: Patients receive indium In 111 radiolabeled anti-CEA MOAB M5A IV over 30 minutes. Patients undergo serial nuclear scans, single photon emission computed tomography (SPECT), and blood and urine sampling over 1 week to estimate absorbed radiation doses to tumor, normal organs (i.e., liver, lung, kidney, and bone marrow), and whole body.
- Treatment: No more than 2 weeks later, patients with adequate biodistribution receive yttrium Y 90 DOTA anti-CEA MOAB M5A IV over 30 minutes on day 1. Patients then undergo serial nuclear scans, SPECT, and blood and urine sampling over 1 week to estimate absorbed radiation doses to tumor, normal organs (i.e., liver, lung, kidney, and bone marrow), and whole body. Treatment repeats every 6-10 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Blood and urine samples are collected periodically for analysis of total activity by radiometric high performance liquid chromatography and to acquire data on antibody metabolism and pharmacokinetics.
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 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed advanced solid tumor for which no standard or effective treatment is available
- •Patients who refuse an available standard but non-curative treatment may also be eligible
- •Tumors must produce CEA as documented by either an elevated serum CEA above the upper limit of normal (ULN) or by immunohistochemical (IHC) methods
- •Positive CEA IHC stain is determined if more than 30% of the tumor cells have an intensity of 2+ or greater
- •Measurable disease
- •Estimated < 1/3 of liver involvement if tumor involves the liver
- •No brain or leptomeningeal involvement with cancer
- •PATIENT CHARACTERISTICS:
- •Karnofsky performance status 60-100%
- •Life expectancy ≥ 3 months
- •WBC ≥ 4,000/μL
- •ANC ≥ 1,500/μL
- •Platelet count ≥ 125,000/μL
- •Creatinine ≤ 1.5 mg/dL and/or creatinine clearance > 60 mL/min
- •Bilirubin ≤ 1.5 mg/dL
- •ALT and AST ≤ 2 times ULN
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Patients currently being treated for severe infections or recovering from other intercurrent illnesses (such as poorly controlled diabetes or hypertension) are ineligible until recovery is deemed complete by the investigator
- •Serum anti-antibody testing must be negative for human anti-humanized antibodies (if patient received prior monoclonal antibody)
- •Serum HIV-negative
- •Serum hepatitis B antigen- and hepatitis C antibody-negative
- •PRIOR CONCURRENT THERAPY:
- •At least 4 weeks since prior radiotherapy, immunotherapy, or chemotherapy (6 weeks for mitomycin C or nitrosoureas) and recovered
- •Recovered from prior major surgery
- •No prior radiotherapy to > 50% of bone marrow
- •No other concurrent chemotherapy, radiotherapy, or immunotherapy
排除标准
- 未提供
结局指标
主要结局
Overall survival
时间窗: From 3 months after treatment completion or until death
Progression-free survival
时间窗: From 3 months after treatment completion until cancer progression or start of another treatment
Time to progression
时间窗: 3 months and six months after treatment completion until cancer progression or start of another treatment
Pharmacokinetic and molecular studies
时间窗: At 0, 1, 4-6, 12-24, 48, 72-120 and 144-168 hours after administration of the baseline imaging dose
Maximum tolerated dose
时间窗: 10 weeks after the beginning of the last cycle of treatment
Toxicity
时间窗: From the date of the beginning of the first cycle of treatment to 10 weeks from the date of the beginning of the last cycle of treatment
次要结局
未报告次要终点