Pilot Trial of Humanized 3S193 Monoclonal Antibody (hu3S193) in Presurgical Patients With Ovarian Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Number of Subjects With Grade 3 Adverse Events
研究概览
简要总结
RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Giving monoclonal antibodies in different ways may kill more tumor cells.
PURPOSE: Phase I trial to study the effectiveness of monoclonal antibody therapy in treating patients who have ovarian cancer.
详细描述
OBJECTIVES: The primary objective iss to determine the safety of indium (111In) monoclonal antibody (mAb) hu3S193 (111In-hu3S193) given intraperitoneally or intravenously in patients with ovarian carcinoma.
Secondary objectives include comparing the localization of 111In-hu3S193 in ovarian cancer tissue after intraperitoneal vs intravenous injection and the biodistribution and pharmacokinetics of this drug when administered intraperitoneally vs intravenously in these patients as well as the formation of human anti-human antibodies (HAHA) in these patients.
OUTLINE: Patients are assigned to 1 of 2 treatment arms on a first come sequential basis. Arm I: Patients receive indium (In 111) monoclonal antibody hu3S193 (111In-hu3S193) intraperitoneally over 30 minutes. Arm II: Patients received 111In-hu3S193 intravenously (IV) over 30 minutes. Patients were to undergo surgical debulking 3-7 days following In 111In-hu3S193 administration, and biopsy samples obtained to assess radioactive uptake. Immunohistochemistry was also to be performed. Blood samples were to be obtained to assess serum radioactivity. Whole body imaging was tp be performed 3 hours after infusion of radiolabeled monoclonal antibody, on the day of surgery, and at one time point in between. Patients were followed for 30 days.
PROJECTED ACCRUAL: A total of 10 patients (5 per arm) were to be accrued for this study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Diagnostic
- 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
- •Cytologic or pathologic diagnosis consistent with ovarian carcinoma. Scheduled to undergo surgical evaluation. Karnofsky performance status of > 60%.
- •Adequate organ function as defined by:
- •Absolute neutrophil count (ANC) > 1.5 x 10^9/L
- •Platelet count > 100 x 10^9/L
- •Bilirubin < 2.0 mg/dL
- •Aspartate aminotransferase (AST) and Alanine transaminase (ALT) < 2.5 X upper limit of normal
- •Serum creatinine < 2.0 mg/dL
- •Forced expiratory volume at one second (FEV1) and forced vital capacity (FVC)> 70% of predicted
- •Left Ventricular Ejection Fraction >50%
- •Recovered from the toxicity of any prior therapy. No evidence of active infection which requires antibiotic therapy. > 18 years of age. Able to sign written informed consent.
排除标准
- •Any significant intercurrent medical problems which may limit the amount of antibody they can tolerate, or render them ineligible for surgery.
- •Clinically significant cardiac disease (New York Heart Association Class III/IV, or abnormalities on ECG that are considered by the investigator to place the patient at increased risk), severe debilitating pulmonary disease, active infections or coagulation disorders.
- •Survival expectancy less than 12 weeks. History of autoimmune hepatitis or history of autoimmune disease. Chemotherapy, radiotherapy, or immunotherapy within four weeks prior to receiving hu3S
- •Psychiatric, addictive or other disorders that compromise the ability to give informed consent.
研究组 & 干预措施
Intraperitoneal (IP) Infusion of 111In-hu3S193
Hu3S193 was administered intraperitoneally at a dose of 5 mg radiolabeled with 5 millicurie (mCi) of 111In.
Patients received 10 mCi 99mTc-sulphur colloid IP administered in 500 ml of normal saline to assure the absence of any loculation or heterogeneous distribution of radioactivity in the peritoneal cavity. A paracentesis catheter was inserted and the hu3S193 was diluted in 100 mL of 5% human serum albumin and administered as a continuous intraperitoneal infusion over 30 minutes. This was followed immediately by 900 mL of normal saline.
干预措施: Monoclonal antibody hu3S193 (Biological)
Intravenous Infusion of 111In-hu3S193
Hu3S193 was to be administered intravenously at a dose of 5 mg radiolabeled with 5 millicurie (mCi) of 111In, diluted in 100 mL of 5% human serum albumin and administered over a 30 minute period.
干预措施: Monoclonal antibody hu3S193 (Biological)
结局指标
主要结局
Number of Subjects With Grade 3 Adverse Events
时间窗: up to 30 days
All toxicities were to be graded according to the Common Toxicity Criteria (CTC) Scale, version 2.0, March 1998.The study was to be terminated upon the occurrence of an adverse event of Grade 3 or greater severity that is considered definitely related to hu3S193.
次要结局
未报告次要终点