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
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.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the MTD and assess the toxicity of IV NAC
The MTD of IV NAC will be defined as one dose level below that which produces NCI 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.
4 years
Yes
Edward A Neuwelt, MD
Principal Investigator
Knight Cancer Institute at Oregon Health & Science University
United States: Food and Drug Administration
OHSU-4229
NCT01138137
June 2010
December 2015
Name | Location |
---|---|
Oregon Health & Science University | Portland, Oregon 97201 |