NCT02094625

NAC to Prevent Cisplatin-induced Hearing Loss

A Dose-Finding Study of N-Acetylcysteine (NAC) to Prevent Cisplatin-induced Hearing Loss in Children With Cancer

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 52 (actual)
• Sponsor: Children's Hospital Los Angeles · Academic / Other
• Sex: All
• Age: 1 Year – 21 Years
• Healthy volunteers: Not accepted

Summary

Cisplatin is a key chemotherapy agent for the treatment of multiple childhood cancers but causes permanent hearing loss. This study investigates the drug N-acetylcysteine (NAC) to determine the dose necessary to protect hearing and also how well tolerated NAC is when combined with chemotherapy.

Detailed description

The study is a dose-finding study of N-acetylcysteine (NAC) to protect hearing in children receiving cisplatin for the treatment of their cancer. NAC also has potential to protect the kidneys from cisplatin toxicity. The study uses a 3+3 dose-escalation scheme to determine the dose of NAC necessary to achieve serum levels consistent with hearing protection in pre-clinical animal models. Three dose levels are predefined. Once the maximum tolerated dose is determined, an expansion cohort will then be enrolled to further evaluate tolerability as well as intra-patient and inter-patient variability in achieved serum levels. An option to enroll in a separate arm for study assessments only is available for those who do not wish to receive NAC. Hearing loss in the cohort will be assessed in the entire cohort in comparison to historical and non-treated children to evaluate for trends toward efficacy.

Conditions

• Neuroectodermal Tumors, Primitive
• Liver Neoplasms
• Osteosarcoma
• Other Childhood Cancers Using Cisplatin-based Regimens

Interventions

Type	Name	Description
DRUG	N-Acetylcysteine	NAC will be administered intravenously over \~60 minutes starting 4 hours following completion of cisplatin chemotherapy. Three dose levels have been pre-determined: Dose Level 1: 225 mg/kg Dose Level 2: 300 mg/kg Dose Level 3: 450 mg/kg Should Dose Level 3 exceed the MTD, the study will examine blood levels of NAC and if below the target blood level necessary for hearing protection, the study will "de-escalate" from Dose Level 3 to an intermediate Dose Level 2.5 and test a dose of 375 mg/kg. As of August 2018: Dose escalation completed with MTD not reached. Dose level 3 (450mg/kg) selected for expansion with NAC.

Timeline

• Start date: 2016-03-01
• Primary completion: 2020-09-01
• Completion: 2021-08-01
• First posted: 2014-03-24
• Last updated: 2023-04-18

Locations

1 site across 1 country: United States