Phase I of Phase I/II Randomized Study of Intraperitoneal tgDCC-E1 and Intravenous Paclitaxel in Women With Platinum-Resistant Ovarian Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Intraperitoneal (IP) tgDCC-E1A in combination with Intravenous (IV) Paclitaxel
研究概览
简要总结
The goal of this clinical research study is to find the highest safe dose of intraperitoneal tgDCC-E1A that can be given in combination with paclitaxel as a treatment for patients with recurrent, platinum-resistant ovarian cancer. How the cancer responds to this treatment will also be studied. Researchers will also ask the patients if they will allow additional tumor samples to be collected and extra blood samples to be drawn. These samples will be used to learn about the biological response before and after treatment.
详细描述
Primary Objective
- To evaluate toxicity and establish the maximum tolerated dose (MTD) of intraperitoneal tgDCC-E1A in combination with intravenous paclitaxel.
- To measure tumor response of intraperitoneal tgDCC-E1A in combination with intravenous paclitaxel and compare to intravenous paclitaxel
Secondary Objective
- To measure time to progression and overall survival.
- To examine the biological effects of combined tgDCC- E1A and paclitaxel in ovarian cancer cells as measured by laboratory testing.
Epithelial ovarian cancer is a significant public health problem. It is the sixth most common cancer in women worldwide. Globally, it is estimated that 162,000 new cases are diagnosed per year, and that 106,000 women die from the disease per year.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Age greater than or equal to 18 years
- •Recurrent epithelial ovarian cancer or primary peritoneal cancer with histologic confirmation of the original tumor. Recurrent disease may be manifested as an elevated cancer antigen (CA)-125 using the following criteria: (a) increase in CA-125 to at least 2 times the upper limit of normal (assayed on 2 occasions at least 7 days apart) for subjects with a history of normal pre-treatment values or values that normalized with the most recent treatment - OR - (b) increase in CA-125 to 2 times the lowest observed value on the most recent treatment (assayed on two occasions at least 7 days apart) for subjects whose CA-125 did not normalize with the most recent treatment.
- •Platinum-resistant disease, defined as recurrence less than six months after discontinuation of treatment with platinum therapy or platinum-refractory disease defined as progression on a platinum-containing regimen.
- •A treatment-free interval of at least three weeks for cytotoxic therapies, radiation therapy, or other experimental drugs prior to first treatment on this protocol.
- •A Zubrod performance status of two or less.
排除标准
- •Previous administration of tgDCC-E1A.
- •Progression on any taxane-containing regimen, or recurrent within 6 months of receiving a weekly taxane-containing regimen.
- •Previous radiation to more than 25% of marrow-bearing areas.
- •Any of the following laboratory values: Hemoglobin <9.0 gm/dl, absolute neutrophil count (ANC) <1.5 K/ml, platelet <100 K/ml, creatinine >2 mg/dl, bilirubin >2 mg/dl, Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT)>2 times the upper limit of normal, or abnormal coagulation profiles (>2 seconds beyond upper range of normal Prothrombin Time (PT) or Partial thromboplastin time (PTT)).
- •Known human immunodeficiency virus (HIV)-positive status or active systemic infection.
- •History of other invasive malignancies, except for non-melanoma skin cancer, unless there is no evidence of other cancer within the past 5 years.
- •Patients with grade 2 or greater neurotoxicity.
- •Patients with unstable angina or those who have had a myocardial infarction within the past six months. Patients with evidence of abnormal cardiac conduction are eligible if their disease has been stable for the past six months. Patients with an ejection fraction under 40%.
研究组 & 干预措施
Arm 1: Paclitaxel + tgDCC-E1A
80 mg/m^2 intravenous Paclitaxel and intraperitoneal (IP) tgDCC-E1A starting dose 1.8 mg DNA/m^2 weekly for six treatments every 7 days.
干预措施: Intraperitoneal tgDCC-E1A (Biological)
Arm 1: Paclitaxel + tgDCC-E1A
80 mg/m^2 intravenous Paclitaxel and intraperitoneal (IP) tgDCC-E1A starting dose 1.8 mg DNA/m^2 weekly for six treatments every 7 days.
干预措施: Paclitaxel (Drug)
Arm 2: Paclitaxel Alone
Weekly single agent intravenous Paclitaxel 80 mg/m^2 for six treatments every 7 days.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Intraperitoneal (IP) tgDCC-E1A in combination with Intravenous (IV) Paclitaxel
时间窗: 6 week cycle (cycle consists of 6 weekly treatments)
Dose combinations assigned using the Continuous Reassessment Method (CRM) with up to 8 cohorts of three subjects each assigned to one of the three tgDCC-E1A dose combinations (1.8 , 3.6 or 5.0 mg DNA/m\^2). Three weeks after third subject started treatment, the number of subjects who experienced dose limiting toxicities (DLT) tabulated. The next cohort of three subjects assigned to same or next higher dose combination using a computer algorithm that evaluates proportion of subjects who experienced a DLT.
次要结局
- Tumor response of intraperitoneal (IP) tgDCC-E1A in combination with intravenous (IV) paclitaxel compared to IV paclitaxel alone(5 Years)