Neoplasms

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Carcinoma

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Carcinoma, Squamous Cell

Head and Neck Neoplasms

Hearing Loss

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Hearing Disorders

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Ear Diseases

Otorhinolaryngologic Diseases

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All Drugs and Chemicals

Lipid Regulating Agents

Cisplatin

Hydroxymethylglutaryl-CoA Reductase Inhibitors

adult patients with head and neck squamous cell carcinoma of the upper aerodigestive tract who will undergo cisplatin chemotherapy with concurrent radiation.

Lisa L Cunningham, Ph.D.

Background:

Cisplatin is a chemotherapy drug. It is used to treat head and neck squamous cell carcinoma (HNSCC) and other cancers. It can cause hearing loss for some people. It is not known how many people will get hearing loss from cisplatin. It is also not known what other factors might influence who gets hearing loss. Factors could include age, sex, noise exposure, and other drugs the person is taking. Statins are drugs used to lower cholesterol. Statins may also reduce cisplatin-induced hearing loss.

Objectives:

To see if statins reduce hearing loss in people getting cisplatin therapy to treat HNSCC. To find out how many people taking cisplatin get hearing loss from it. To find out if other factors might influence whether cisplatin causes hearing loss.

Eligibility:

People ages 18 and older who are getting treatment with cisplatin for HNSCC

Design:

Participants will be screened with a review of their medical records.

Participants will have 3 visits. These will be before the onset of cisplatin therapy, at about 4 weeks after they finish therapy, and about 6 months after they finish therapy. Each visit will include:

Medication history

Audiogram/hearing tests. Participants will wear headphones and indicate when they hear different sounds.

Questions about their noise exposure history and whether they have ringing in the ears

Objectives:

* Primary: Determine whether head and neck cancer patients taking statin drugs for hyperlipidemia are at decreased risk of cisplatin-induced hearing loss.
* Secondary: Determine the incidence and severity of hearing loss in head and neck cancer patients undergoing low-dose, weekly cisplatin chemotherapy with concurrent radiation. Hearing loss with this more recent cisplatin regimen has not been thoroughly evaluated in the literature. Examine whether age, gender, pre-existing hearing loss, other medications, or comorbid medical conditions may be risk factors for cisplatin-induced hearing loss and/or the acquisition or progression of tinnitus in this patient population.

Study Population:

-Subjects will be adult patients with head and neck squamous cell carcinoma of the upper aerodigestive tract who will undergo cisplatin chemotherapy with concurrent radiation.

Design:

* Observational study
* 334 subjects will be enrolled.
* Subjects will complete a questionnaire to estimate the degree of prior noise exposure and impact on baseline hearing. Information on medical comorbidities, names and doses of current medications will be obtained from the medical record and verified at each subject visit.
* Subjects will complete self-administered audiograms using FDA-approved software from SHOEBOXTM Audiometry on a portable tablet (iPad) computer.
* Audiograms will be completed prior to commencing chemoradiation, within 4 weeks of completing treatment, and 6 months after completing treatment.
* Subjects will also complete a validated tinnitus questionnaire with each audiogram. A noise exposure history will be collected during the initial study visit and verified during subsequent visits. Any indicated changes to the subject s noise exposure history will be added to record.
* No investigational or experimental therapy will be given as part of this protocol.
* Audiograms will be performed at the Johns Hopkins Suburban Outpatient Center or the NIH Clinical Center.
* Two interim analyses will be conducted prior to study completion (after N=88 and N=176 subjects completing the protocol) to determine whether there are statistically significant differences in severity or incidence of hearing loss in subjects taking concurrent statin drugs vs. subjects who are not taking statin drugs.

Outcome Measures:

* Primary outcome measure: The primary outcome measure is the change in hearing sensitivity (as measured by the self-administered audiogram) 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 TUNE and ASHA criteria and will be compared in subjects taking statin drugs vs. subjects not taking statin drugs. Hearing status will be compared between audiograms collected at baseline (prior to treatment) to a repeated audiogram at the end of treatment (within 4 weeks of cisplatin protocol cessation).
* Secondary outcome measure: Secondary outcome measures include 1) changes in hearing sensitivity between the first post-cisplatin audiogram and the second post-cisplatin audiogram, and 2) changes in scores on the tinnitus questionnaire between the pre-treatment audiogram and the two post-treatment audiograms.

Hearing Loss and the Effects of Statin Drugs in People With Head and Neck Squamous Cell Carcinoma Treated With Cisplatin Chemoradiation

Observational Study of Hearing Loss and the Effects of Statin Drugs in Head and Neck Squamous Cell Carcinoma Patients Treated With Cisplatin Chemoradiation

The primary outcome measure is the change in hearing sensitivity (as measured by the self-administered audiogram) 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 TUNE and ASHA criteria and will be compared in subjects taking statin drugs vs. subjects not taking statin drugs. Hearing status will be compared between audiograms collected at baseline (prior to treatment) to a repeated audiogram at the end of treatment (within 4 weeks of cisplatin protocol cessation).

Secondary outcome measures include 1) changes in hearing sensitivity between the first post-cisplatin audiogram and the second post-cisplatin audiogram, and 2) changes in scores on the tinnitus questionnaire between the pre-treatment audiogram and the two post-treatment audiograms.

National Institute on Deafness and Other Communication Disorders (NIDCD)

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Lymphoma

Leukemia

Lymphosarcoma

Vincristine

Adult survivors who developed persistent treatment-related neuropathy.

Adult survivors who did not develop persistent treatment-related neuropathy.

William E. Evans, PharmD

This observational study is designed to establish induced pluripotent stem cells (iPSCs) from childhood cancer survivors who did or did not develop persistent treatment-induced peripheral neuropathy, from which to make human neurons for comparing their sensitivity to vincristine and other potentially neurotoxic drugs.

Investigators will assess the effects of inherited genome variations on treatment-induced peripheral neuropathy that persists in adults who were cured of childhood cancer. Cells from childhood cancer survivors who did or did not develop drug-induced neuropathy will be isolated and induced to become neurons. Cell sensitivity to anticancer agents will be tested in both groups and compared to determine if the survivors have genetic variants that correspond to those identified in companion genomic studies. This will assist in determining if gene variants increase the risk of treatment-induced neurotoxicity.

The investigators are interested in detecting changes of phenotype pre-post treatment in each group (cases, controls) respectively, as well in comparing the pre-post treatment phenotypic changes between the two groups (cases vs. controls).

Participants will be recruited from an existing protocol at St. Jude (SJLIFE, NCT00760656). Complete neuropathic evaluations are obtained as part of SJLIFE, and the information will be shared for use in the SJLPSC study. A one-time blood draw will be obtained, and peripheral blood mononuclear cells (PBMC's) will be isolated for eventual creation of induced pluripotent stem cells (iPSC) that will be differentiated into human neurons. These human neurons will allow the investigators to functionally validate and further interrogate CEP72 genetic variants or variants in other genes that are associated with persistent (or acute) vincristine neuropathy using a "state of the art" cellular model of human neurons. Furthermore, creating neurons from patients at the extremes (highly sensitive to vincristine-induced neuropathy and matched controls) allows the study of differences at baseline and after treatment with vincristine.

PRIMARY OBJECTIVE:

* To establish induced pluripotent stem cells (iPSCs) from childhood cancer survivors who did or did not develop persistent treatment-induced peripheral neuropathy, from which to make human neurons to assess their sensitivity to vincristine and determine whether neurons from patients who developed neuropathy are more sensitive to vincristine or other neurotoxic chemotherapy.

SECONDARY OBJECTIVE:

* To evaluate the iPSC neurons made from patients with persistent treatment-related neuropathy and iPSC neurons from patients who did not develop neuropathy from the same treatment, for phenotypic difference prior to and after exposure to vincristine or other potentially neurotoxic medications.

Blood samples will be obtained from each cohort.

iPSC Neurons From Adult Survivors of Childhood Cancer Who Have Persistent Vincristine-Induced Neuropathy

Collection of PBMC's From Patients With Unusually Severe Vincristine-Induced Neuropathy for the Creation of Neuronal-Like Cells

Blood will be drawn on Day 1, processed and sent to the University of Chicago for infectious diseases testing and creation of PBMCs for eventual development of iPS cells.

Cell phenotypes of the iPSC neurons made from each patient (case or control) will be observed before and after treatment of neurotoxic drugs, giving for each drug a pair of observations from a patient.

Study title	NCT ID	Conditions	Eligibility	Organization
Hearing Loss and the Effects of Statin Drugs in People With Head and Neck Squamous Cell Carcinoma Treated With Cisplatin Chemoradiation	NCT03225157	Head and Neck N... Hearing Disorde... Hyperlipidemia	18 Years -	National Institutes of Health Clinical Center (CC)
Hearing Loss and the Effects of Statin Drugs in People With Head and Neck Squamous Cell Carcinoma Treated With Cisplatin Chemoradiation	NCT03225157	Head and Neck N... Hearing Disorde... Hyperlipidemia	18 Years -	National Institutes of Health Clinical Center (CC)
iPSC Neurons From Adult Survivors of Childhood Cancer Who Have Persistent Vincristine-Induced Neuropathy	NCT02564484	Leukemia Lymphoma	18 Years -	St. Jude Children's Research Hospital

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