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

NCT ID: NCT01138137

Last Updated: 2017-04-21

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2014-12-31

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

All subjects

Group Type: EXPERIMENTAL

Paclitaxel

Intervention Type: DRUG

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

N-acetylcysteine

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

Dose: 100mg/m2 infused IP on day 2 of each 3 week cycle 60 min after the NAC infusion

6 treatment cycles

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

Cisplatin

Dose: 100mg/m2 infused IP on day 2 of each 3 week cycle 60 min after the NAC infusion

6 treatment cycles

Intervention Type: DRUG

Other Intervention Names

NAC

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

OHSU Knight Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Edward Neuwelt

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Edward A Neuwelt, MD

Role: PRINCIPAL_INVESTIGATOR

Knight Cancer Institute at Oregon Health & Science University

Locations

Oregon Health & Science University

Portland, Oregon, United States

Countries

United States

Other Identifiers

4229

Identifier Type: OTHER

Identifier Source: secondary_id

SOL-08005-L

Identifier Type: OTHER

Identifier Source: secondary_id

OHSU-4229

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00004229

Identifier Type: -

Identifier Source: org_study_id