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

Primary Purpose

Hearing Loss, Head and Neck Cancer

Status

Not yet recruiting

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Atorvastatin

Placebo

About this trial

This is an interventional treatment trial for Hearing Loss focused on measuring Audiogram, Statin, Chemotherapy, Squamous Cell Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 and availability for the duration of the study
Ability to provide consent and provision of signed and dated informed consent form
Adult patients, male or female, aged >=18
Diagnosed with squamous cell carcinoma of the head and neck, confirmed by a pathologic review of surgical or biopsy specimen(s), who meet standard clinical and laboratory criteria and will undergo treatment with concomitant cisplatin-based chemotherapy and radiation with curative intent. This includes patients who will be treated with either intensity-modulated radiation therapy (IMRT) or proton radiotherapy, with planned dose to the cochlea <35 Gy (to limit confounding effects of radiation 64-67). Patients 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.
Subjects must have hearing thresholds at or better than 70 dB HL at 1, 2, and 4 kHz in at least one ear at the time of their baseline audiogram
Baseline laboratory tests with lab values <1.5x the upper limit of normal: aspartate aminotransferase (AST or SGOT); alanine aminotransferase; creatine phosphokinase, creatinine
Ability to take oral medication by mouth or by feeding tube and willingness to adhere to the daily atorvastatin or placebo regimen
For females of reproductive potential: use of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during study participation and for an additional 8 weeks after the end of atorvastatin administration

EXCLUSION CRITERIA:

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

Patients already taking a statin drug
Patients with a flat, Type B tympanogram
Patients with bilateral cochlear implants
Patients with a history of prior treatment with platinum chemotherapy drugs
Patients for whom additional adjuvant platinum-based chemotherapy is planned after the completion of concomitant chemoradiation (e.g., patients with nasopharyngeal carcinoma)
Staff members of the NIDCD Sections and of the lead site investigators headed by the PIs
Children will be excluded because HNSCC in children under age 18 is exceedingly rare
Current use of cimetidine, spironolactone, ketoconazole, cyclosporine, or protease inhibitors
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 increase risk to safety or ability to complete study
Expected concomitant use of aminoglycoside antibiotics

Sites / Locations

Winship Cancer Institute at Emory University
University of Maryland Medical Center
National Institutes of Health Clinical Center
Wilmot Cancer Institute at the University of Rochester Medical Center in New Yor

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

No Intervention

Arm Label

Arm Description

randomization to either placebo or atorvastin

observational

Outcomes

Primary Outcome Measures

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).

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

To examine the extent to which other statin drugs (and other doses of atorvastatin) reduce the incidence and severity of cisplatin-induced hearing loss in patients with head and neck squamous cell carcinoma

The secondary 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 in the observational arm of the study. Hearing loss will be defined according to CTCAE criteria and will be compared in subjects taking: 1) any statin other than atorvastatin vs. subjects not taking any statin drug, 2) subjects taking atorvastatin at doses other than 20 mg vs. subjects not taking any statin. Hearing sensitivity will be compared between audiograms collected at baseline (prior to treatment) to a repeated audiogram at the end of treatment (within 4 months of cessation of cisplatin administration).

Full Information

NCT ID

NCT04915183

First Posted

June 4, 2021

Last Updated

October 24, 2023

Sponsor

National Institute on Deafness and Other Communication Disorders (NIDCD)

1. Study Identification

Unique Protocol Identification Number

NCT04915183

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 9, 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

October 30, 2023 (Anticipated)

Primary Completion Date

March 1, 2025 (Anticipated)

Study Completion Date

December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Institute on Deafness and Other Communication Disorders (NIDCD)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

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 2 visits. One before starting cisplatin treatment and within 3 months of completing 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. Participants in the interventional arm will have 2 additional 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 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 daily dose of atorvastatin vs. a placebo among individuals undergoing cisplatin therapy to treat head and neck cancer. Objectives: Primary Objective: To determine the effectiveness of atorvastatin (40 mg) at reducing the incidence of a CTCAEv5.0 Grade >=2 hearing loss in patients treated with cisplatin-based CRT for head and neck squamous cell carcinoma (HNSCC). Exploratory Objective: To determine if concomitant atorvastatin (40 mg) use alters disease-free survival or overall survival in subjects undergoing cisplatin-based CRT. Endpoints: Primary Endpoint: The primary endpoint is the change in hearing sensitivity as measured by pure-tone audiometry between the pre-treatment (before cisplatin-based CRT) hearing test and the post-treatment (after completion of cisplatin- based CRT) audiogram. Hearing loss will be defined according to CTCAEv5.0 Grade >=2 criteria and will be compared in subjects taking atorvastatin (40 mg) 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. Exploratory Endpoint: The exploratory endpoint is the overall and disease-free survival at 2 years after cisplatinbased CRT. Overall survival and disease-free median survival will be compared between subjects taking atorvastatin (40 mg) vs. those taking placebo.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hearing Loss, Head and Neck Cancer

Keywords

Audiogram, Statin, Chemotherapy, Squamous Cell Carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

186 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Other

Arm Description

randomization to either placebo or atorvastin

Arm Title

Arm Type

No Intervention

Arm Description

observational

Intervention Type

Drug

Intervention Name(s)

Atorvastatin

Intervention Description

For the interventional arm of the study, subjects will be provided with atorvastatin (20 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.

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

placebo will be formulated to also contain a white powder such that the atorvastatin and placebo are indistinguishable even if a capsule is opened.

Primary Outcome Measure Information:

Title

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).

Description

Time Frame

Baseline (prior to treatment) to a repeated audiogram at the end of treatment (within 2-4 months of cessation of cisplatin administration).

Secondary Outcome Measure Information:

Title

Description

Time Frame

Baseline (prior to treatment) to a repeated audiogram at the end of treatment (within 4 months of cessation of cisplatin administration).

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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 and availability for the duration of the study Ability to provide consent and provision of signed and dated informed consent form Adult patients, male or female, aged >=18 Diagnosed with squamous cell carcinoma of the head and neck, confirmed by a pathologic review of surgical or biopsy specimen(s), who meet standard clinical and laboratory criteria and will undergo treatment with concomitant cisplatin-based chemotherapy and radiation with curative intent. This includes patients who will be treated with either intensity-modulated radiation therapy (IMRT) or proton radiotherapy, with planned dose to the cochlea <35 Gy (to limit confounding effects of radiation 64-67). Patients 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. Subjects must have hearing thresholds at or better than 70 dB HL at 1, 2, and 4 kHz in at least one ear at the time of their baseline audiogram Baseline laboratory tests with lab values <1.5x the upper limit of normal: aspartate aminotransferase (AST or SGOT); alanine aminotransferase; creatine phosphokinase, creatinine Ability to take oral medication by mouth or by feeding tube and willingness to adhere to the daily atorvastatin or placebo regimen For females of reproductive potential: use of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during study participation and for an additional 8 weeks after the end of atorvastatin administration EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: Patients already taking a statin drug Patients with a flat, Type B tympanogram Patients with bilateral cochlear implants Patients with a history of prior treatment with platinum chemotherapy drugs Patients for whom additional adjuvant platinum-based chemotherapy is planned after the completion of concomitant chemoradiation (e.g., patients with nasopharyngeal carcinoma) Staff members of the NIDCD Sections and of the lead site investigators headed by the PIs Children will be excluded because HNSCC in children under age 18 is exceedingly rare Current use of cimetidine, spironolactone, ketoconazole, cyclosporine, or protease inhibitors 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 increase risk to safety or ability to complete study Expected concomitant use of aminoglycoside antibiotics

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Katharine A Fernandez, Au.D.

Phone

(301) 496-5699

katharine.fernandez@nih.gov

First Name & Middle Initial & Last Name or Official Title & Degree

Lisa L Cunningham, Ph.D.

Phone

(301) 443-2766

cunninghamll@mail.nih.gov

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lisa L Cunningham, Ph.D.

Organizational Affiliation

National Institute on Deafness and Other Communication Disorders (NIDCD)

Official's Role

Principal Investigator

Facility Information:

Facility Name

Winship Cancer Institute at Emory University

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Nicole Schmitt

Phone

404-778-0278

nicole.cherie.schmitt@emory.edu

Facility Name

University of Maryland Medical Center

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21201

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ronna Hertzano

Phone

410-328-1892

rhertzano@som.umaryland.edu

Facility Name

National Institutes of Health Clinical Center

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20892

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

Phone

800-411-1222

Ext

TTY8664111010

prpl@cc.nih.gov

Facility Name

Wilmot Cancer Institute at the University of Rochester Medical Center in New Yor

City

Rochester

State/Province

New York

ZIP/Postal Code

14642

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Shawn Newlands

Phone

585-275-5823

Shawn_Newlands@urmc.rochester.edu

12. IPD Sharing Statement

Links:

URL

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2021-DC-0002.html

Description

NIH Clinical Center Detailed Web Page

Learn more about this trial

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

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