NCT01138137

N-acetylcysteine Given IV With Cisplatin and Paclitaxel in Patients With Ovarian Cancer

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

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: OHSU Knight Cancer Institute · Academic / Other
• Sex: Female
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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. OUTLINE: Subjects will undergo chemotherapy for epithelial ovarian cancer with paclitaxel IV, 135 mg/m2 (Day 1) and IP cisplatin 100 mg/m2 (Day2), followed by Taxol IP, 60 mg/m2 (Day 8) every 3 weeks for 6 courses. Sixty minutes prior to each course of IP cisplatin, IV NAC (starting at 150 mg/kg) will be infused over 30 minutes. A dose escalation schema for NAC will be followed. Toxicity to the therapy will be graded according to the Common Terminology Criteria for Adverse Events.

Conditions

• Ovarian Carcinoma, Stage 3 or 4
• Epithelial Ovarian Carcinoma
• Primary Peritoneal Carcinoma

Interventions

Type	Name	Description
DRUG	Paclitaxel	Dose: 135mg/m2 infused IV on Day 1 of 3 week cycle Dose: 60mg/m2 infused IP on Day 8 of 3 week cycle 6 treatment cycles
DRUG	N-acetylcysteine	A group of 5 subjects will be evaluated at each dose level. On Day 2 of each 3 week cycle, subject receives IV NAC followed by IP cisplatin. 6 treatment cycles Dose escalation schema: Level 1: 150mg/kg Level 2: 300mg/kg Level 3: 600mg/kg Level 4: 800mg/kg Level 5: 1000mg/kg Level 6: 1200mg/kg
DRUG	Cisplatin	Dose: 100mg/m2 infused IP on day 2 of each 3 week cycle 60 min after the NAC infusion 6 treatment cycles

Timeline

• Start date: 2010-06-01
• Primary completion: 2014-12-01
• Completion: 2014-12-01
• First posted: 2010-06-07
• Last updated: 2017-04-21

Locations

1 site across 1 country: United States