Epithelial Ovarian Carcinoma, Ovarian Carcinoma, Stage 3 or 4, Primary Peritoneal Carcinoma
Conditions
Keywords
ovarian cancer, epithelial ovarian cancer, peritoneal cancer
Brief 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.
Interventions
DRUGPaclitaxel
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
DRUGN-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
DRUGCisplatin
Dose: 100mg/m2 infused IP on day 2 of each 3 week cycle 60 min after the NAC infusion 6 treatment cycles
Sponsors
OHSU Knight Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To determine the MTD and assess the toxicity of IV NAC | 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. |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Countries
United States
Outcome results
None listed