Single-Dose, Cohort Study of Increasing Doses of Yttrium-90 Conjugated to Humanized Monoclonal Antibody 3S193 (90Y-hu3S193) in Patients With Advanced Ovarian Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Number of Patients With Dose-limiting Toxicities (DLTs)
研究概览
简要总结
RATIONALE: Radiolabeled monoclonal antibodies can locate tumor cells and deliver radioactive tumor-killing substances to them without harming normal cells. Giving radiolabeled monoclonal antibody directly into the abdominal cavity may kill more tumor cells.
PURPOSE: Phase I trial to study the effectiveness of giving radiolabeled monoclonal antibody therapy directly into the abdominal cavity in treating patients who have advanced ovarian epithelial cancer.
详细描述
OBJECTIVES:
Primary
- Determine the safety and maximum tolerated dose of intraperitoneally (IP) administered yttrium-90 (90Y) radiolabeled monoclonal antibody (mAB) hu3S193 (90Y-hu3S193) in patients with advanced ovarian epithelial cancer.
Secondary
- Determine the localization and whole body and abdominal clearance of 90Y-hu3S193 using indium-111 (111In) radiolabeled hu3S193 and gamma camera imaging.
- Determine the serum pharmacokinetics of hu3S193 using gamma well counting.
- Determine the antibody response as measured by human anti-human antibody response (HAHA).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Histologically confirmed non-mucinous ovarian adenocarcinoma.
- •Persistent or recurrent intraperitoneal cancer following platinum/taxane-based therapy for Stage 3 ovarian cancer.
- •Patients with residual disease < 2cm will be candidates for this study.
- •The following laboratory and clinical results within the last 2 weeks prior to study day 1:
- •Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L; Platelet count ≥ 100 x 10^9/L; Serum bilirubin ≤ 2.0 mg/dL; Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN); Alanine aminotransferase (ALT) ≤ 2.5 x ULN; Serum creatinine ≤2.0 mg/dL; Forced expiratory volume (FEV1) ≥60% of predicted; Forced vital capacity (FVC) ≥60% of predicted; Diffusion capacity ≥55% of predicted; Left ventricular ejection fraction (LVEF) ≥50%;
- •Karnofsky performance status ≥
- •Before any trial-specific procedures or treatment can be performed, the patient or legally authorized guardian or representative must give witnessed written informed consent for participation in the trial.
- •Placement of an intra-abdominal catheter at the time of surgery.
排除标准
- •Active parenchymal disease (i.e., Stage IV International Federation of Gynecology and Obstetrics (FIGO) classification).
- •Presence of symptomatic extra abdominal metastases.
- •Known central nervous system (CNS) tumor involvement.
- •Clinically significant heart disease (New York Heart Association Class III or IV).
- •ECG demonstrating clinically significant arrhythmias or evidence of prior myocardial infarction.
- •Other serious illnesses, eg, serious infections requiring antibiotics, bleeding disorders that may limit the amount of antibody they can tolerate or render them ineligible for surgery.
- •Chronic inflammatory bowel disease.
- •Chemotherapy, biologic therapy, or immunotherapy within 4 weeks prior to enrollment.
- •Pregnancy or lactation.
- •Patients who are positive for human anti-human antibodies (HAHA) and/or who have received a murine monoclonal antibody.
研究组 & 干预措施
Cohort 1
Patients received a single intraperitoneal (IP) dose of 10 mg of hu3S193 radiolabeled with 10 millicuries (mCi) 90Y and 5mCi 111In-hu3S193 to enable imaging after dosing.
干预措施: 111In-hu3S193 (Biological)
Cohort 1
Patients received a single intraperitoneal (IP) dose of 10 mg of hu3S193 radiolabeled with 10 millicuries (mCi) 90Y and 5mCi 111In-hu3S193 to enable imaging after dosing.
干预措施: 90Y-hu3S193 (Biological)
Cohort 2
Patients received a single intraperitoneal (IP) dose of 10 mg of hu3S193 radiolabeled with 15 millicuries (mCi) 90Y and 5mCi 111In-hu3S193 to enable imaging after dosing.
干预措施: 90Y-hu3S193 (Biological)
Cohort 2
Patients received a single intraperitoneal (IP) dose of 10 mg of hu3S193 radiolabeled with 15 millicuries (mCi) 90Y and 5mCi 111In-hu3S193 to enable imaging after dosing.
干预措施: 111In-hu3S193 (Biological)
结局指标
主要结局
Number of Patients With Dose-limiting Toxicities (DLTs)
时间窗: Up to day 56
All adverse events were graded according to the National Cancer Institute Common Toxicity Criteria (CTC) Scale (Version 2.0, published April 30, 1999). DLT was defined as: * Any Grade 3 or greater non-hematological toxicity (except for alopecia, nausea, and vomiting, defined separately below) * Any Grade alopecia * Grade 4 nausea or vomiting ≥ 5 days duration. * Any Grade 4 hematological toxicity (except for toxicity of ≤ 5 days duration without growth factor, platelet, or transfusion support). To be dose limiting, an adverse event must be definitely, probably, or possibly related to the administration of the investigational agent.
次要结局
- Clearance as Measured by the Half-life (T1/2) of the Elimination Phase(Up to 22 days)
- Number of Patients With Human Anti-human Antibodies (HAHA) After Treatment(Up to day 56)