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

• INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria evaluated by the study team, including an on-site oncologist:

• Willingness and ability to comply with and participate in all study procedures andavailability for the duration of the study

• Ability to provide consent and provision of signed and dated informed consent form

• Adult subjects, aged >=18

• Diagnosed with squamous cell carcinoma of the head and neck, confirmed by apathologic review of surgical or biopsy specimen(s), who meet standard clinical andlaboratory criteria and will undergo treatment with concomitant cisplatin-basedchemotherapy and radiation with curative intent or treatment with neoadjuvantchemotherapy (NAC). This includes subjects who will be treated with eitherintensity-modulated radiation therapy (IMRT) or proton radiotherapy, with planneddose to the cochlea <35 Gy (to limit confounding effects of radiation64-67).Patients receiving immunotherapy in addition to cisplatin chemoradiation areeligible. Subjects treated with either high-dose cisplatin (typically 100 mg/m^2 x 2-3 doses every three weeks) or low-dose, weekly cisplatin (typically 40 mg/m^2 x 6-7 doses weekly) may enroll. Cisplatin in the neo-adjuvant setting may be givenwithin a combination chemotherapy regimen (e.g TPF= Docetaxel, Cisplatin and 5FU orDC = Docetaxel Cisplatin)

• Subjects must have hearing thresholds at or better than 70 dB HL at 1, 2, and 4 kHzin at least one ear at the time of their baseline audiogram. CTCAE criteria (primaryendpoint) and ASHA criteria (secondary endpoint) are based on changes in hearing inat

least one ear with one ototoxicity event/grade assigned per person.

• Baseline laboratory tests with lab values <1.5x the upper limit of normal: aspartateaminotransferase (AST or SGOT); alanine aminotransferase; creatine phosphokinase,creatinine

• Ability to take oral medication by mouth or by feeding tube and willingness toadhere to the daily atorvastatin or placebo regimen

• For females of reproductive potential: use of highly effective contraception for atleast 1 month prior to enrollment and agreement to use such a method during studyparticipation and for an additional 8 weeks after the end of atorvastatinadministration

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

• Subjects currently taking a statin drug

• Subjects with bilateral flat, Type B tympanogram

• Subjects with bilateral cochlear implants

• Pre-existing liver or kidney disease that in the opinion of the investigator wouldinterfere with taking Atorvastatin 40 mg daily.

• Subjects with a history of prior treatment with cisplatin chemotherapy

• Staff members of the NIDCD Sections and of the lead site investigators headed by thePIs

• Children will be excluded because HNSCC in children under age 18 is exceedingly rare

• Current use of cimetidine, spironolactone, ketoconazole, cyclosporine, proteaseinhibitors, gemfibrozil, clarithromycin or itraconazole

• Pregnancy, lactation, or plan to become pregnant

• Known allergic reactions to components of atorvastatin or the placebo

• Other severe or unstable medical conditions which clinical site PI believes increaserisk to safety or ability to complete study

• Expected concomitant use of aminoglycoside antibiotics