Cisplatin-induced Cochlear and Vestibular Damage in Head and Neck Cancer

Cisplatin-induced Cochlear and Vestibular Damage in Head and Neck Squamous Cell Carcinoma: A Cohort Study

The goal of this observational study is to learn about the occurrence of and to identify suitable strategies for screening and monitoring of inner ear damage in patients receiving cisplatin chemoradiotherapy for head and neck cancer. Researchers will compare patients who are receiving cisplatin chemoradiotherapy to patients who are only receiving radiotherapy. Patients will undergo standardized testing for hearing loss, tinnitus and vestibular dysfunction at baseline, during and after treatment. Optional genetic analyses will aim to identify genes known to predispose to cisplatin-induced ototoxicity.

Study Overview

• Status: Not yet recruiting
• Conditions: Head and Neck Cancer; Squamous Cell Carcinoma of the Head and Neck; Hearing Loss; Deafness; Dizzyness; Vestibular Disease; Cisplatin Ototoxicity; Ototoxic Hearing Loss; Inner Ear Hearing Loss; Ototoxicity, Drug-Induced; Cisplatin-induced Hearing Loss

• Study Type: Observational
• Enrollment (Estimated): 55

Contacts and Locations

• Study Contact: Name: Prof. Dr. med. Simon Jäger; Phone Number: +49 911-398-2822; Email: simon.jaeger@klinikum-nuernberg.de
• Study Contact Backup: Name: Dr. Chantal Degen, MSc; Phone Number: +49 911-398-112583; Email: chantal.degen@klinikum-nuernberg.de

Study Locations

• Germany
  • Bavaria
    • Nuremberg, Bavaria, Germany, 90419
      • Klinikum Nuremberg
      • Contact: Prof. Dr. med. Simon Jäger; Phone Number: +49 911-398-2822; Email: simon.jaeger@klinikum-nuernberg.de
      • Contact: Dr. Christine Le Roux, MBChB; Email: christine.leroux@klinikum-nuernberg.de
      • Contact: Prof. Dr. med. Simon Jäger
      • Contact: Dr. Chantal Degen, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with head and neck squamous cell carcinoma receiving treatment with cisplatin chemoradiotherapy or only radiotherapy at Klinikum Nuremberg in Nuremberg, Germany.

Description

Inclusion Criteria:

• Diagnosis of head and neck squamous cell carcinoma
• Cisplatin-based chemoradiotherapy (monotherapy or combination-therapy, adjuvant or neo-adjuvant) or only radiotherapy (control group)
• Age 18 to 85 years
• Signed agreement and willingness to participate in the study and adhere to the study protocol

Exclusion Criteria:

• Severe hearing impairment (WHO grade 3 or 4, corresponding to an audiometric ISO value of ≥61 dB in the better ear at frequencies of 500, 1000, 2000 and 4000 Hz)
• Self-reported tinnitus or vestibular dysfunction in the last 3 months (only lead to exclusion of the corresponding secondary objectives, not to complete exclusion from the study)
• Current cochlear implant
• Concurrent treatment with loop diuretics (e.g. furosemide), aminoglycoside antibiotics or other known ototoxic substances in the last three months
• Acute psychosis or serious psychiatric illness
• Addiction disorder

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Cisplatin chemoradiotherapy; Adult patients with head and neck squamous cell carcinoma receiving cisplatin chemotherapy and radiotherapy.
Only radiotherapy; Adult patients with head and neck squamous cell carcinoma receiving only radiotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tinnitus	Incidence and severity of new or exacerbated tinnitus during treatment with cisplatin chemotherapy measured as impairment according to the Tinnitus Handicap Inventory (THI) score: 0-16 = no impairment. 18-36 = mild impairment. 38-56 = moderate impairment. 58-76 = severe impairment. 78-100 = catastrophic impairment.	From enrollment prior to treatment initiation to the last follow-up circa 3 months after completion of treatment.
Hearing loss	Incidence of significant hearing loss during treatment with cisplatin chemotherapy described according to CTCAE (Common Terminology Criteria for Adverse Events) in 1-8 kHz audiogram: Grade 1 = threshold shift 15-25 dB in 2 contiguous test frequencies in at least one ear. Grade 2 = threshold shift >25 dB in 2 contiguous test frequencies in at least one ear. Grade 3 = threshold shift of >25 dB averaged at 3 contiguous test frequencies in at least one ear. Grade 4 = decrease in hearing to profound bilateral loss, absolute threshold >80 dB at 2 kHz and above.	From enrollment prior to treatment initiation to the last follow-up circa 3 months after treatment completion.
Vestibular dysfunction	Incidence of dizziness or balance disturbances during treatment with cisplatin chemotherapy as determined through the Dizziness Handicap Inventory (DHI); changes of >18 indicates a clinical relevant worsening in condition: 0-29 = no to mild impairment. 30-60 = moderate impairment. >60 = severe impairment.	From enrollment prior to treatment initiation to the last follow-up circa 3 months after treatment completion.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Description of hearing loss through further testing	Description of hearing loss requiring treatment according to the Freiburger Einsilber hearing test (≤80% of speech recognition is an indication for hearing aid): proportion of patients with loss of distortion product otoacoustic emissions (DPOAEs) and new hearing loss in high frequency audiometry at 8 - 16 kHz. Investigating the usefulness of high frequency audiometry when compared to DPOAEs for early recognition of ototoxicity.	From enrollment prior to treatment initiation to the last follow-up circa 3 months after treatment completion.
Description of vestibular damage manifesting as worsening dizzyness or imbalance during treatment with cisplatin	Clinically relevant vestibulopathy: Increase in dizzyness symptoms >18 points on the Dizziness Handicap Inventory (DHI) together with instrumentally measurable pathological changes in vestibular function: Decrease in VOR-Gain in the video head impulse test (vHIT) (from ca. 1 by 0,2 to 0,8) or new overt or covert saccades.; Decrease in caloric excitability by more than 20%.; Increase in non-elicitable vestibular evoked myogenic potentials (VEMPs) during therapy or a new amplitude asymmetry of more than 50%; prolongation of VEMP latency by more than 0.2 ms.	From enrollment prior to treatment initiation to the last follow-up circa 3 months after treatment completion.
Description of the incidence and type of cisplatin dose-limiting toxicities	Dose-limiting nephrotoxicity, myelosuppression, gastrointestinal side effects (gingival deposits, stomatitis, diarrhoea, severe vomiting), fever, cisplatin-induced polyneuropathy [documented as AESI].; Correlation between median cumulative cisplatin dose and adverse effects.	From enrollment prior to treatment initiation to the last follow-up circa 3 months after treatment completion.
Assessment of tumour-related quality of life	Completion of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30 + HN43).	From enrollment prior to treatment initiation to the last follow-up circa 3 months after treatment completion.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic variants related to cisplatin-induced ototoxicity	Prevalence of genetic variants that are predicitve and/or protective of inner ear damage during treatment with cisplatin chemotherapy (optional - patients can choose to only take part in the main study and not in the genetic analysis).	Once-off blood sample taken simultaneously with any of the routine blood samples during treatment, can be at any point from study enrollment to the last follow-up visit circa 3 months after treatment completion.

Collaborators and Investigators

• Sponsor: Simon Jäger
• Collaborators: Klinikum Nürnberg

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: April 7, 2025
• First Submitted That Met QC Criteria: April 14, 2025
• First Posted (Actual): April 16, 2025

Study Record Updates

• Last Update Posted (Actual): April 16, 2025
• Last Update Submitted That Met QC Criteria: April 14, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Wounds and Injuries; Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Chemically-Induced Disorders; Neoplasms, Squamous Cell; Otorhinolaryngologic Diseases; Sensation Disorders; Ear Diseases; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Hearing Disorders; Labyrinth Diseases; Squamous Cell Carcinoma of Head and Neck; Ototoxicity; Carcinoma; Carcinoma, Squamous Cell; Vestibular Diseases; Head and Neck Neoplasms; Hearing Loss; Deafness; Hearing Loss, Sensorineural; Dizziness
• Other Study ID Numbers: CPN_PMU002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No