Clinical trial NCT01138137: N-acetylcysteine Given IV With Cisplatin and Paclitaxel in Patients With Ovarian Cancer
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Ovarian Carcinoma, Stage 3 or 4
Epithelial Ovarian Carcinoma
Primary Peritoneal Carcinoma
Keywords: ovarian cancer
epithelial ovarian cancer
peritoneal cancer
Lead sponsor: OHSU Knight Cancer Institute
Sponsor class: OTHER
First posted: 2010-06-07
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: To determine the MTD and assess the toxicity of IV NAC
timeFrame: 4 years
Secondary outcomes:
measure: To describe tumor response
timeFrame: 4 years
measure: To describe the incidence and severity of nephrotoxicity
timeFrame: 4 years
measure: To describe the incidence and severity of hearing loss
timeFrame: 4 years
measure: To describe the incidence and severity of peripheral and autonomic neuropathy
timeFrame: 4 years
Other outcomes:
Locations:
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
Study officials:
affiliation: Knight Cancer Institute at Oregon Health & Science University
name: Edward A Neuwelt, MD
role: PRINCIPAL_INVESTIGATOR
References: