Sodium Thiosulfate for the Prevention of Ototoxicity in Patients With Locally Advanced Squamous Cell Cancer of the Head and Neck Undergoing Chemoradiation With Cisplatin
Sodium Thiosulfate for the Prevention of Ototoxicity in Patients With Locally Advanced Squamous Cell Cancer of the Head and Neck Undergoing Chemoradiation With Cisplatin
This phase II trial investigates how well sodium thiosulfate works in preventing ototoxicity
 (hearing loss/damage) in patients with squamous cell cancer of the head and neck that has
 spread to nearby tissue or lymph nodes (locally advanced) who are undergoing a
 chemoradiation. Sodium thiosulfate is a type of medication used to treat cyanide poisoning
 and to help lessen the side effects from cisplatin. Chemotherapy drugs, such as cisplatin,
 work in different ways to stop the growth of tumor cells, either by killing the cells, by
 stopping them from dividing, or by stopping them from spreading. Giving chemotherapy with
 radiation therapy may kill more tumor cells. The purpose of this trial is to find out whether
 it is feasible to give sodium thiosulfate 4 hours after each cisplatin infusion along with
 standard of care radiation therapy in patients with head and neck cancer. Giving sodium
 thiosulfate after cisplatin may help decrease the risk of hearing loss.
PRIMARY OBJECTIVE:

 I. To establish feasibility of intravenous sodium thiosulfate (STS) after each dose of
 concurrent cisplatin in patients with locally advanced head and neck squamous cell carcinoma
 undergoing definitive radiotherapy.

 SECONDARY OBJECTIVES:

 I. To determine the rate of grade >= 2 change from baseline based on Common Terminology
 Criteria for Adverse Events (CTCAE) version 5 with use of STS after concurrent chemoradiation
 with cisplatin 3 months post-treatment.

 II. To determine the rate of tinnitus measured by Patient Reported Outcomes (PRO)-CTCAE with
 use of STS 3 months post-treatment.

 III. To describe patient reported outcomes with STS measured with PRO-CTCAE for selected
 oral, gastrointestinal (GI), neurologic and perceptual symptoms.

 IV. To describe patient reported outcomes measured with Hearing Handicap Inventory for Adults
 - Screening (HHIA-S) compared to results from standard NRG Oncology head and neck trials
 (such as Radiation Therapy Oncology Group (RTOG) 1016).

 OUTLINE: Patients are assigned to 1 of 2 groups per treating physician's discretion.

 COHORT A: Patients undergo standard of care radiation therapy daily for 6-7 weeks. Patients
 receive cisplatin intravenously (IV) on day 1. Between 4-5 hours after each cisplatin
 infusion, patients also receive sodium thiosulfate IV over 1-2 hours on day 1. Treatment
 repeats every 7 days for up to 7 cycles in the absence of disease progression or unacceptable
 toxicity.

 COHORT B: Patients undergo standard of care radiation therapy daily for 6-7 weeks. Patients
 receive high-dose cisplatin IV on day 1. Between 4-5 hours after each cisplatin infusion,
 patients also receive sodium thiosulfate IV over 1-2 hours on day 1. Treatment repeats every
 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

 After completion of study treatment, patients are followed up every 3 months for up to 3
 years.
Inclusion Criteria:

 -  Participants must have histologically or cytologically confirmed locoregionally
 advanced squamous cell carcinomas of mucosal surfaces of head and neck who are being
 treated with concurrent chemoradiation with cisplatin

 -  Participants must be eligible for cisplatin-based concurrent chemotherapy in
 conjunction with at least 6 weeks of daily fractionated radiation therapy

 -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 50%)

 -  Absolute neutrophil count >= 1,000/microliter (mcL)

 -  Platelets >= 100,000/mcL

 -  Total bilirubin within normal institutional limits, unless elevated due to Gilbert's
 syndrome and direct bilirubin is within normal limits

 -  Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase (SGOT)) =< 3
 X institutional upper limit of normal

 -  Alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase (SGPT)) =< 3 X
 institutional upper limit of normal

 -  Creatinine =< 1.5 x within institutional upper limit of normal OR creatinine clearance
 glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2, calculated using the
 Cockcroft-Gault equation, unless data exists supporting safe use at lower kidney
 function values, no lower than 30 mL/min/1.73 m^2

 -  Ability to understand a written informed consent document, and the willingness to sign
 it

 -  Individuals with a prior or concurrent malignancy whose natural history or treatment
 does not have the potential to interfere with the safety or efficacy assessment of the
 investigational regimen are eligible for this trial

 -  The effects of sodium thiosulfate (STS) on the developing human fetus are unknown. For
 this reason and because cisplatin used in this trial are known to be teratogenic,
 women of childbearing potential and men must agree to use adequate contraception such
 as hormonal and/or barrier method of birth control for the duration of study
 participation and for 3 months after last administration of study treatment. Should a
 woman become pregnant or suspect she is pregnant while she or her partner is
 participating in this study, she should inform her treating physician immediately. Men
 treated or enrolled on this protocol must also agree to use adequate contraception
 prior to the study, for the duration of study participation, and 3 months after last
 administration of study treatment

 -  Normal or mild hearing impairment at baseline (CTCAE grade =< 1)

 Exclusion Criteria:

 -  Participants that are not eligible for cisplatin-based chemoradiation for reasons such
 as chronic kidney disease, severe hearing loss, and severe peripheral neuropathy

 -  Uncontrolled inter-current illness or psychiatric illness/social situation that would
 limit compliance with study requirements

 -  Has known hypersensitivity to cisplatin, sodium thiosulfate or any of its excipients

 -  Participants with uncompensated congestive heart failure New York Heart Association
 (NYHA) class 3 or above

 -  Participants who cannot get secure venous access using either a Mediport or a
 peripherally inserted central catheter (PICC) line for safe administration of
 intravenous sodium thiosulfate

 -  Pregnant women are excluded from this study because cisplatin is a cytotoxic agent
 with the potential for teratogenic or abortifacient effects. Because there is an
 unknown but potential risk for adverse events in nursing infants secondary to
 treatment of the mother with cisplatin or sodium thiosulfate, breastfeeding should be
 discontinued if the mother is treated with either agent