Cancer and Hearing Loss Related in Children

NCT02425397 | Completed

• 1 other identifier: 2010-A00405-34
• Study Type: observational
• Target: 119
• Locations: 1 country
• Sites: 1

Brief Summary

A limited number of relatively contradictory studies have suggested that the development of serious ototoxicity in children treated with cisplatin or, more rarely, carboplatin could be partly related to genetic risk factors affecting detoxification enzymes and membrane transporters of platinum derivatives. The objective of this study is therefore to identify genetic variants associated with the development of platinum ototoxicity in patients treated with cisplatin or carboplatin (minimum follow-up of 3 years) for one of the following diseases: neuroblastoma, hepatoblastoma, retinoblastoma, malignant germ cell tumour, osteosarcoma, high-risk or recurrent Wilms' tumour, non-parameningealrhabdomyosarcoma. A total of 180 patients, corresponding to 60 cases with grade 3 or 4 ototoxicity and 120 controls with no signs of ototoxicity (separate complete audiograms for each ear) will be included. A saliva sample will be used to obtain DNA for pharmacogenetic studies. The value of this study will be to define a population at high risk of developing ototoxicity in order to adapt treatment, or even develop preventive treatment of ototoxicity based on antioxidant medications

Conditions

Cancer in Children; Hearing Loss

Keywords

Ototoxicity; platinum derivatives; paediatrics; oncology; clinical research

Outcome Measures

Primary Outcomes (1)

• genetic factors (drug metabolism enzymes, membrane transporters) predisposing to cisplatin and carboplatin ototoxicity in children

  Day 0

Secondary Outcomes (2)

• genetic factors predisposing to aminoglycoside ototoxicity;

  Day 0

• To provide a rationale for prevention of ototoxicity by the use of antioxidant medications.

  Day 0

Study Arms (2)

patients with grade 3 or 4 Brock ototoxicity

Genetic: Genetic study

patients controls with no signs of ototoxicity

Genetic: Genetic study MT-RN1

Interventions

Genetic study GENETIC

study of mutations of metabolic enzymes and membrane transport genes, which will be performed by sequencing.

patients with grade 3 or 4 Brock ototoxicity

Genetic study MT-RN1 GENETIC

study of mutations of the mitochondrial gene MT-RN1, which will be performed by sequencing.

patients controls with no signs of ototoxicity

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

180 patients will be included : 60 patients with grade 3 or 4 Brockototoxicityand 120 patients controls with no signs of ototoxicity (separate complete audiograms for each ear)

You may qualify if:

• previous treatment with cis-or carboplatin
• Age equal to or greater than 4 years
• the presence of a separate complete audiogram for each ear in order to define the Brock grade
• informed and written consent of both parents or legal guardian
• affiliation of the child to a social security scheme
• To patients:
• previous treatment with platinum compounds for neuroblastoma, hepatoblastoma, pancreatoblastoma, retinoblastoma, germ cell tumor malignant osteosarcoma, Wilms high risk or relapsed non para-meningeal rhabdomyosarcoma with ototoxicity grade 3 or 4 Brock (Grade 3 - 40dB to 2000 Hz; Grade 4-40 dB at 1000 Hz) To patients controls
• previous treatment with platinum compounds for neuroblastoma, hepatoblastoma, pancreatoblastoma, retinoblastoma, germ cell tumor malignant osteosarcoma, Wilms high risk or recurrence rhabdomyosarcoma non parameningeal without ototoxicity (grade 0 Brock)
• minimum follow-up of 3 years after stopping treatment

You may not qualify if:

• patients with brain tumor
• patients with tumor "paraméningée" (such as rhabdomyosarcoma of the rock)
• patients with renal toxicity (≥ Grade 2) at the time of treatment with platinum-based
• patients with pathological pre-treatment assessment of hearing
• chemotherapy during
• patients with cerebral or total body irradiation (Total Body Irradiation)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Institut Curie

Paris, 75005, France

Location

Related Publications (1)

• Lui G, Bouazza N, Denoyelle F, Moine M, Brugieres L, Chastagner P, Corradini N, Entz-Werle N, Verite C, Landmanparker J, Sudour-Bonnange H, Pasquet M, Verschuur A, Faure-Conter C, Doz F, Treluyer JM. Association between genetic polymorphisms and platinum-induced ototoxicity in children. Oncotarget. 2018 Jul 20;9(56):30883-30893. doi: 10.18632/oncotarget.25767. eCollection 2018 Jul 20.

  PMID: 30112115 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Saliva

MeSH Terms

Conditions

Neoplasms; Hearing Loss; Ototoxicity

Interventions

Genetic Association Studies

Condition Hierarchy (Ancestors)

Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Genetic Techniques; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2014
• First Posted: April 24, 2015
• Study Start: March 27, 2011
• Primary Completion: January 5, 2016
• Study Completion: January 5, 2016
• Last Updated: December 1, 2025

Record last verified: 2025-11

Locations

FR (1)