NCT04915183

Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer

Phase II Interventional Study Using Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 224 (estimated)
• Sponsor: National Institute on Deafness and Other Communication Disorders (NIDCD) · NIH
• Sex: All
• Age: 18 Years – 100 Years
• Healthy volunteers: Not accepted

Summary

Background: Cisplatin is used to treat head and neck cancer. People who take this drug are at risk for hearing loss. Atorvastatin is a drug used to treat high cholesterol. It might reduce the risk of cisplatin-induced hearing loss. Objective: To find out if atorvastatin reduces hearing loss in people treated with cisplatin and radiation. Eligibility: People ages 18 and older with squamous cell carcinoma of the head and neck who will undergo treatment with cisplatin-based chemotherapy and radiation Design: Participants will be screened with their medical records. Participants currently taking a cholesterol-lowering statin medication are invited to participate in the observational arm of the study. Those not taking such a medication are invited to participate in the interventional arm of the study. All participants will have 3 study visits for the purpose of evaluating hearing. One before starting cisplatin treatment, one within 3 months of completing cancer treatment, and one within 2 years of completing cancer treatment. They will have tympanograms. A small flexible tip will be placed in the ear canal. A puff of air will be delivered to assess mobility of the ear drum. They will have hearing tests. They will wear headphones. They will listen to tones that vary in loudness. They will be asked to indicate when they hear a sound. They will complete 3 questionnaires at the time of each hearing test. Participants will have 2 visits for blood tests. These will occur upon consent and 12 weeks after. They will be randomly assigned to take the study drug or placebo orally, once daily. They will take it during cisplatin treatment and for 3 months after treatment. Long-term follow up will include a chart review 2 years after participants complete their cisplatin therapy.

Detailed description

Study Description: Individuals undergoing cisplatin-based chemotherapy are at risk for developing significant, permanent hearing loss. The cholesterol-lowering drug atorvastatin has the potential to reduce the incidence and severity of hearing loss, as evidenced by our preclinical data in mice and our retrospective data in humans. Here we will compare hearing changes between subjects on a concurrent 40 mg daily dose of atorvastatin vs. a placebo among individuals undergoing cisplatin-based chemotherapy to treat head and neck cancer. Objectives: Primary Objective: To determine the effectiveness of atorvastatin (40 mg) in subjects treated with cisplatin-based chemotherapy for head and neck squamous cell carcinoma (HNSCC) at reducing moderate changes in hearing sensitivity relative to baseline, as defined by CTCAEv5.0 Grade\>=2 criteria. Secondary Objectives: * To determine disease-free survival and overall survival in subjects undergoing cisplatin-based chemotherapy. * To determine whether atorvastatin increases grade 3-5 treatment emergent adverse events versus placebo * To determine the effectiveness of atorvastatin (40 mg) at reducing changes in hearing sensitivity relative to baseline, as defined by ASHA criteria, in subjects treated with cisplatin- based chemotherapy for head and neck squamous cell carcinoma (HNSCC). Endpoints: Primary Endpoint: The incidence of hearing loss at 12 +/-4 weeks after completion of cisplatin-based chemotherapy). Hearing loss will be defined according to CTCAEv5.0 Grade \>=2 criteria based on changes in sensitivity relative to baseline, in at least one ear, across 1, 2, 3, 4, 6 and 8 kHz and will be compared in subjects taking atorvastatin (40 mg) vs. subjects taking placebo. Secondary Endpoints: * Overall and disease-free survival at 2 years after cisplatin-based chemotherapy. Overall survival and disease-free median survival will be compared between subjects taking atorvastatin (40 mg) vs. those taking placebo. * Incidence of new CTCAEv5.0 grade \> 3 AEs through 12 weeks after chemotherapy in the placebo and atorvastatin arms. * Incidence of hearing loss at 12 +/- 4 weeks after completion of cisplatin-based chemotherapy. Hearing loss will be defined according to ASHA criteria based on changes in sensitivity relative to baseline, in at least one ear, across 1, 2, 3, 4, 6, 8, 10, and 12.5 kHz and will be compared in subjects taking atorvastatin (40 mg) vs. subjects taking placebo.

Conditions

• Hearing Loss
• Head and Neck Cancer

Interventions

Type	Name	Description
OTHER	Placebo	Placebo will be formulated to also contain a white powder such that the atorvastatin and placebo are indistinguishable even if a capsule is opened.
DRUG	Atorvastatin	Subjects will be provided with atorvastatin (40 mg) or placebo to be taken daily by mouth or by feeding tube. The tablets may be taken whole or crushed according to patient swallowing capabilities and preference.

Timeline

• Start date: 2024-07-10
• Primary completion: 2028-08-01
• Completion: 2030-08-31
• First posted: 2021-06-07
• Last updated: 2026-03-09

Locations

5 sites across 1 country: United States

Regulatory

• FDA-regulated drug study