Phase I Dose Escalation Study of N-acetylcysteine (NAC) Administered Intravenously (IV) in Conjunction With Intraperitoneal (IP) Administered Cisplatin and IV/IP Paclitaxel in Patients With Stage III or IV Ovarian Cancer
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- To determine the MTD and assess the toxicity of IV NAC
研究概览
简要总结
RATIONAL FOR STUDYING IV NAC AS POTENTIAL CHEMOPROTECTANT:
Cisplatin has shown efficacy in the treatment of subjects with epithelial ovarian cancer. Systemic toxicities associated with cisplatin include nephro, oto, and nerve toxicities. It may be possible to reduce the toxicities of cisplatin by administering it in conjunction with IV NAC. NAC may reduce cisplatin related nephro, oto, and nerve toxicities without compromising the effectiveness of the chemotherapy against the ovarian cancer cells. It is possible that this combination of drugs may in the future allow ovarian cancer patients to receive the full series of IP cisplatin-paclitaxel chemotherapy, with fewer side effects and improved survival.
It is hypothesized that the proposed treatment of stage III or IV epithelial ovarian cancer with IP cisplatin and IV/IP paclitaxel in conjunction with IV NAC will limit the neurotoxicity, nephrotoxicity and ototoxicity that is associated with cisplatin administration.
详细描述
OBJECTIVES:
PRIMARY:
To determine the Maximum Tolerated Dose (MTD) and assess the toxicity of IV NAC in conjunction with IP cisplatin and IV/IP paclitaxel in subjects with stage 3 or 4 epithelial ovarian cancer that has been surgically debulked
SECONDARY:
- To describe tumor response in subjects receiving treatment for previously debulked stage 3 or 4 epithelial ovarian cancer with IP cisplatin, IV/IP paclitaxel , and IV NAC.
- To describe the incidence and severity of nephrotoxicity (Creatinine Clearance (CrCl)) in subjects undergoing treatment for stage 3 or 4 epithelial ovarian cancer with IP cisplatin, IV paclitaxel and IV NAC and who have had their disease surgically debulked.
- To describe the incidence and severity of hearing loss in subjects undergoing treatment for stage 3 or 4 epithelial ovarian cancer with IP cisplatin, IV/IP paclitaxel and IV NAC and who have had their disease surgically debulked.
- To describe the incidence and severity of peripheral and autonomic neuropathy in subjects undergoing treatment for stage 3 or 4 epithelial ovarian cancer with IP cisplatin, IV/IP Taxol and IV NAC and who have had their disease surgically debulked.
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 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Signed written informed consent in accordance with institutional guidelines
- •Histologically confirmed diagnosis of stage 3 or 4 epithelial ovarian or primary peritoneal carcinoma
- •Have had debulking surgery with optimal tumor cytoreduction
- •Standard treatment offered for ovarian cancer including systemic or intraperitoneal cisplatin with systemic taxane-based chemotherapy
- •Age ≥ 18 years to ≤ 75 years
- •Laboratory testing within 14 days of registration:
- •White blood cell count ≥ 2.5 x 103/mm3
- •Absolute granulocyte count ≥ 1.2 x 103/mm3
- •Platelets ≥ 100 x 103/mm3
- •Creatinine < 1.8
- •Bilirubin < 2.0
- •Serum glutamate oxaloacetate transaminase (SGOT)/Serum glutamate pyruvate transaminase (SGPT) < 2.5 x institutional upper limits of normal
- •Performance status must be Eastern Cooperative Oncology Group (ECOG) < 2 (Karnofsky ≥ 50)
- •Life expectancy of ≥ 60 days from the date of registration
排除标准
- •Pregnant, positive beta human chorionic gonadotropin (hCG), or lactating
- •History of clinically significant reactive airway disease
- •Active significant cardiac disease as evidenced by New York Heart Association Classification for chronic heart failure (CHF), Class III or IV
- •Uncontrolled (over the last 30 days) clinically significant confounding medical conditions
- •Allergies or other contraindications to IP cisplatin, IV Taxol, or IV NAC.
研究组 & 干预措施
All subjects
干预措施: Paclitaxel (Drug)
All subjects
干预措施: N-acetylcysteine (Drug)
All subjects
干预措施: Cisplatin (Drug)
结局指标
主要结局
To determine the MTD and assess the toxicity of IV NAC
时间窗: 4 years
The MTD of IV NAC will be defined as one dose level below that which produces NCI Common Toxicity Criteria (CTC) grade 3 or 4 non-hematologic toxicity in 20% of subjects. The toxicity of NAC can be differentiated from that of the chemotherapeutic drugs as the half-life of NAC is very short and adverse effects are seen either during or very soon after the administration of NAC.
次要结局
- To describe tumor response(4 years)
- To describe the incidence and severity of nephrotoxicity(4 years)
- To describe the incidence and severity of hearing loss(4 years)
- To describe the incidence and severity of peripheral and autonomic neuropathy(4 years)
研究者
Edward Neuwelt
Professor
OHSU Knight Cancer Institute