Clinical trial
A Dose-Finding Study of N-Acetylcysteine (NAC) to Prevent Cisplatin-induced Hearing Loss in Children With Cancer
Name
CCI-14-00270
Description
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.
Trial arms
Trial start
2016-03-01
Estimated PCD
2020-09-01
Trial end
2021-08-01
Status
Completed
Phase
Early phase I
Treatment
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.
Arms:
N-Acetylcysteine Intervention
Other names:
N-acteylcysteine, acteylcysteine injectable, Acetadote
Size
52
Primary endpoint
Target Serum Level NAC
On average up to 4 weeks from diagnosis
Eligibility criteria
Inclusion Criteria:
* Are between 1 and 21 years of age (inclusive) at time of diagnosis of underlying malignancy
* Have a new diagnosis of a localized malignancy with a planned treatment course to include at least two cycles of cisplatin
* Diagnosis to be assigned by oncology attending of record (may be reported via designee), histological diagnosis does not need to be confirmed separately
* Most common but not exclusive diagnoses consist of hepatoblastoma, medulloblastoma, osteosarcoma
* Total cumulative dose of planned cisplatin must be \>200 mg/m2 (or 6.67 mg/kg equivalent for infants requiring weight-based dosing. Conversion factor used is 30:1).
* Cisplatin must be delivered over \<3 days
* Planned cisplatin dose to be infused over ≤6 hours for ≤2 days per cycle
* Are anticipated to be able to comply with end-of-therapy audiology assessment (note that hearing assessments are performed per routine clinical care in children receiving cisplatin and consist of an audiogram or auditory brainstem response, and distortion-product otoacoustic emissions)
* Patients with any hearing status are eligible for study (as long as they can comply with the study primary aims of assessing toxicity and dose-response)
Exclusion Criteria:
* no preexisting risk of serious arrhythmia as defined by (a) normal sinus rhythm on electrocardiogram and corrected QT interval \<500 and (b) no previous history of congenital arrhythmia (e.g. Wolf-Parkinson-White)
* Hepatic, biliary, cardiac, or bone marrow function inadequate for chemotherapy as per patient's treatment regimen. There are no additional protocol-specific restrictions for these markers.
* Moderate or Severe Persistent Asthma as defined by the latest recommendations from the National Heart Lung and Blood Institute definition includes daily asthma exacerbation with need for rescue medication) or an overnight hospitalization for asthma exacerbation within the previous 28 days
* Disseminated disease (e.g. lepto-meningeal spread, tumor metastases)
* Karnofsky or Lansky score \<50%
* Pregnancy or breast-feeding mothers
* Documented hypersensitivity or allergy to previous NAC infusion
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 52, 'type': 'ACTUAL'}}
Updated at
2023-04-18
1 organization
Organization
Children's Hospital Los Angeles