N-acetylcysteine Given IV With Cisplatin and Paclitaxel in Patients With Ovarian Cancer
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.
|Ovarian Carcinoma, Stage 3 or 4 Epithelial Ovarian Carcinoma Primary Peritoneal Carcinoma||Drug: Paclitaxel Drug: N-acetylcysteine Drug: Cisplatin||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||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|
- To determine the MTD and assess the toxicity of IV NAC [ Time Frame: 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.
- To describe tumor response [ Time Frame: 4 years ]
- To describe the incidence and severity of nephrotoxicity [ Time Frame: 4 years ]
- To describe the incidence and severity of hearing loss [ Time Frame: 4 years ]
- To describe the incidence and severity of peripheral and autonomic neuropathy [ Time Frame: 4 years ]
|Study Start Date:||June 2010|
|Study Completion Date:||December 2014|
|Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
|Experimental: All subjects||
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
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
Other Name: NACDrug: Cisplatin
Dose: 100mg/m2 infused IP on day 2 of each 3 week cycle 60 min after the NAC infusion
6 treatment cycles
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
- 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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01138137
|United States, Oregon|
|Oregon Health & Science University|
|Portland, Oregon, United States, 97239|
|Principal Investigator:||Edward A Neuwelt, MD||Knight Cancer Institute at Oregon Health & Science University|