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

NCT01138137 | Withdrawn Phase 1 DMC

• 4 other identifiers: IRB000042294229SOL-08005-LOHSU-4229
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

ovarian cancer; epithelial ovarian cancer; peritoneal cancer

Outcome Measures

Primary Outcomes (1)

• 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 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.

  4 years

Secondary Outcomes (4)

• 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

Study Arms (1)

All subjects

EXPERIMENTAL

Drug: Paclitaxel; Drug: N-acetylcysteine; Drug: Cisplatin

Interventions

Paclitaxel 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

All subjects

N-acetylcysteine 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

Also known as: NAC

All subjects

Cisplatin DRUG

Dose: 100mg/m2 infused IP on day 2 of each 3 week cycle 60 min after the NAC infusion 6 treatment cycles

All subjects

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead

Study Sites (1)

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Carcinoma, Ovarian Epithelial

Interventions

Paclitaxel; Acetylcysteine; Cisplatin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Amino Acids; Amino Acids, Peptides, and Proteins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Edward A Neuwelt, MD

  Knight Cancer Institute at Oregon Health & Science University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 3, 2010
• First Posted: June 7, 2010
• Study Start: June 1, 2010
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: April 21, 2017

Record last verified: 2017-04

Locations

US (1)