A PHASE II TRIAL OF Hu3S193 THERAPY FOR PATIENTS WITH PLATINUM REFRACTORY OR PLATINUM RESISTANT EPITHELIAL OVARIAN, PRIMARY PERITONEAL AND FALLOPIAN TUBE CANCER
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 31
- 试验地点
- 16
- 主要终点
- Best Overall Response
研究概览
简要总结
RATIONALE: Monoclonal antibodies, such as Hu3S193, 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 II trial is studying how well Hu3S193 works in treating patients with ovarian epithelial cancer, fallopian tube cancer, or peritoneal cavity cancer.
详细描述
OBJECTIVES:
Primary
- To evaluate the efficacy of monoclonal antibody Hu3S193 in women with platinum-resistant/refractory ovarian, fallopian tube, or primary peritoneal cancer, based on RECIST criteria (Response Evaluation Criteria in Solid Tumors).
Secondary
- To determine the safety of the study drug.
- To determine the drug pharmacokinetics when administered in multiple weekly injections.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed ovarian epithelial, fallopian tube, or primary peritoneal carcinoma
- •Progressive disease
- •Disease must express Lewis-Y antigen documented by immunohistochemistry in archived or fresh primary or metastatic tumor biopsies
- •Measurable disease, including at least one measurable lesion, according to RECIST criteria or CA-125 (Cancer Antigen-125) > 2 times upper normal limit
- •Pleural effusion, ascites, bone metastases, and lesions located in previously irradiated areas are not considered measurable
- •Disease must be considered platinum-refractory or resistant, meeting any of the following criteria:
- •Platinum-refractory defined as progression during the initial platinum-based chemotherapy regimen or failure to achieve a complete response (e.g., stable disease or partial response) with evidence of progressive disease (by physical examination, radiological exams, or CA-125) during the initial platinum-based chemotherapy
- •Platinum-resistant defined as recurrence within six months of completion of the initial platinum-based regimen (primary platinum-resistance) or recurrence after six months of completion of the initial platinum-based regimen (still considered platinum-sensitive, but incurable by any approach, that will progress to a secondary platinum-resistance scenario) and failure to ≥ 1 re-induction with a platinum-based regimen (secondary platinum-resistance)
- •No high tumor burden, as assessed by the investigator
- •No rapidly progressing disease, as assessed by clinical evaluation
- •No known CNS (Central Nervous System) involvement by tumor
- •PATIENT CHARACTERISTICS:
- •Inclusion criteria:
- •Karnofsky performance status > 70%
- •Life expectancy ≥ 12 weeks
- •ANC (absolute neutrophil count) ≥ 1,500/mm³
- •Platelet count ≥ 100,000/mm³
- •Serum bilirubin ≤ 2.0 mg/dL
- •AST (aspartate aminotransferase) and ALT (alanine aminotransferase) ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN if with liver metastases)
- •Creatinine ≤ 2.0 mg/dL
- •Prothrombin time < 1.3 times control
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
排除标准
- •NYHA (New York Heart Association) class III or IV heart disease
- •Clinically significant arrhythmias by ECG
- •Myocardial infarction within the past 6 months
- •Any other serious illness, including any of the following:
- •Severe ascites
- •Severe active infections requiring antibiotics
- •Bleeding disorders
- •Chronic inflammatory bowel disease
- •Diseases that might interfere with the collection of accurate results from this study
- •Positive for human anti-human antibodies
- •Prior history of tumor (excluding adequately treated nonmelanoma skin cancer or carcinoma in situ of the uterine cervix)
- •Uncontrolled hypercalcemia (i.e., > 11.5 mg/dL)
- •PRIOR CONCURRENT THERAPY:
- •See Disease Characteristics
- •Recovered from the toxic effects of any prior therapy
- •No concurrent systemic steroids or immunosuppressant agents
- •No more than 1 prior non-platinum-containing regimen for the treatment of platinum-resistant/refractory disease
- •Patients who receive 2 or more different non-platinum-containing chemotherapy regimens for platinum-resistant/refractory disease are not eligible
- •More than 4 weeks since prior and no other concurrent chemotherapy, radiotherapy, radiopharmaceuticals (e.g., ^32P), biological therapy, anti-estrogen therapy (including tamoxifen), immunotherapy, or surgery
- •More than12 weeks since prior investigational agent
- •No prior treatment with a murine or humanized antibody and/or antibody fragment
结局指标
主要结局
Best Overall Response
时间窗: From start of study treatment until the end of Cycle 1 (8 weeks), Cycle 2 (16 weeks) or Cycle 3 (24 weeks).
Best response recorded from the start of treatment until disease progression/recurrence. Includes all patients evaluable for efficacy, regardless of used criteria: RECIST or CA-125 (Cancer Antigen 125). Evaluation of target lesions: Complete Response (CR), resolution of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter (LD sum) of target lesions, taking as reference the baseline LD sum; Progressive Disease (PD), a 20% increase in LD sum of target lesions or the appearance of new lesion(s); Stable Disease (SD), no sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD. Evaluation of non-target lesions: CR, resolution of all non-target lesions and normalization of CA-125 level; SD, persistence of one or more non-target lesions and/or maintenance of CA-125 level above the normal limits; PD, appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
次要结局
- Number of Participants With Adverse Events and Serious Adverse Events(From the first dose of investigational product up to 30 days after the last dose of investigational product)
- Number of Participants With Adverse Events Reasonably Related to the Investigational Product (Incidence Greater Than 5%).(From the first dose of investigational product up to 30 days after the last dose of investigational product)
- Mean Cmax and Cmin of Hu3S193 Relating to the First 4 Doses.(Pre-dose (within 10 minutes) and Post-dose (5 minutes after completion of infusion) on weeks 1, 2, 3, and 4 of Cycle 1.)
- Mean Cmax and Cmin of Hu3S193 Relating to the First 8 Doses(Pre-dose (within 10 minutes) and Post-dose (5 minutes after completion of infusion) on weeks 1, 2, 3, 4, 5, 6, 7 and 8 of Cycle 1.)