Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
- Conditions
- Hearing LossHead and Neck Cancer
- Interventions
- Other: Placebo
- Registration Number
- NCT04915183
- Lead Sponsor
- National Institute on Deafness and Other Communication Disorders (NIDCD)
- Brief 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 chemoradiation therapy (CRT) 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 CRT to treat head and neck cancer.
Objectives:
Primary Objective: To determine the effectiveness of atorvastatin (40 mg) in subjects treated with cisplatin-based CRT 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 CRT.
* 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 CRT 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 CRT). 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 CRT. 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 CRT in the placebo and atorvastatin arms.
* Incidence of hearing loss at 12 +/-4 weeks after completion of cisplatin-based CRT. 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 224
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1 Atorvastatin Atorvasatatin (40 mg) 2 Placebo Placebo
- Primary Outcome Measures
Name Time Method To determine the effectiveness of atorvastatin (20 mg) at reducing the incidence and severity of cisplatin-induced hearing loss in patients with head and neck squamous cell carcinoma (HNSCC). Baseline (prior to treatment) to a repeated audiogram at the end of treatment (within 2-4 months of cessation of cisplatin administration). The primary endpoint is the change in hearing sensitivity (as measured by pure-tone audiometry) between the pre-treatment (before cisplatin therapy) hearing test and the post-treatment (after completion of cisplatin therapy) audiogram. Hearing loss will be defined according to CTCAE criteria and will be compared in subjects taking atorvastatin vs. subjects not taking any statin drug. Hearing sensitivity will be compared between audiograms collected at baseline (prior to treatment) to a repeated audiogram at the end of treatment (within 2-4 months of cessation of cisplatin administration).
- Secondary Outcome Measures
Name Time Method To compare the incidence of grade (Bullet)3 AEs through 4 weeks after CRT with atorvastatin versus placebo. Another secondary endpoint will be the incidence of grade (Bullet)3 AEs, which are expected to occur with CRT but rarely with atorvastatin. It is important to confirm that atorvastatin does not increase the overall toxicity associated with CRT.
To examine the extent to which atorvastatin 40 mg alters overall survival and disease-free survival. The overall survival and disease-free survival will be assessed at 3 months, 1 and 2 years after cisplatin-based CRT. Overall complete clinical response, comparing subjects taking atorvastatin (40 mg) vs those taking placebo. It is important to confirm that atorvastatin use does not reduce overall response, survival or disease- free survival in subjects with HNSCC. To date, only two retrospective studies have compared survival in HNSCC subjects taking statins.
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 CRT for head and neck squamous cell carcinoma (HNSCC). The incidence of hearing loss at 12 4 weeks after completion of cisplatin-based CRT. Hearing loss will be defined according to ASHA criteria, comparing subjects taking atorvastatin (40 mg) vs. placebo. The American Speech-Langauge-Hearing Association (ASHA) ototoxicity criteria can be used for early detection based on changes in hearing sensitivity in extended high frequencies (\>8 kHz). While ASHA does not assign grades to indicate severity, it may provide early diagnosis of hearing loss that has not yet spread to speech-related frequency regions of the cochlea (\<8 kHz).
Trial Locations
- Locations (4)
Winship Cancer Institute at Emory University
🇺🇸Atlanta, Georgia, United States
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States
Wilmot Cancer Institute at the University of Rochester Medical Center in New Yor
🇺🇸Rochester, New York, United States