Sodium Thiosulfate in Preventing Ototoxicity for Squamous Cell Cancer Patients Undergoing Chemoradiation With Cisplatin

NCT04541355 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 20208NCI-2020-05752
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Clinical Stage III Human Papillomavirus (HPV)-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8; Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8; Locally Advanced Head and Neck Squamous Cell Carcinoma; Locally Advanced Hypopharyngeal Squamous Cell Carcinoma; Locally Advanced Laryngeal Squamous Cell Carcinoma; Locally Advanced Oral Cavity Squamous Cell Carcinoma; Locally Advanced Oropharyngeal Squamous Cell Carcinoma; Pathologic Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8; Pathologic Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8; Stage III Hypopharyngeal Carcinoma AJCC v8; Stage III Laryngeal Cancer AJCC v8; Stage III Lip and Oral Cavity Cancer AJCC v8; Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8; Stage IV Hypopharyngeal Carcinoma AJCC v8; Stage IV Laryngeal Cancer AJCC v8; Stage IV Lip and Oral Cavity Cancer AJCC v8; Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC v8; Stage IVA Hypopharyngeal Carcinoma AJCC v8; Stage IVA Laryngeal Cancer AJCC v8; Stage IVA Lip and Oral Cavity Cancer AJCC v8; Stage IVA Oropharyngeal (p16-Negative) Carcinoma AJCC v8; Stage IVB Hypopharyngeal Carcinoma AJCC v8; Stage IVB Laryngeal Cancer AJCC v8; Stage IVB Lip and Oral Cavity Cancer AJCC v8; Stage IVB Oropharyngeal (p16-Negative) Carcinoma AJCC v8; Stage IVC Hypopharyngeal Carcinoma AJCC v8; Stage IVC Laryngeal Cancer AJCC v8; Stage IVC Lip and Oral Cavity Cancer AJCC v8; Stage IVC Oropharyngeal (p16-Negative) Carcinoma AJCC v8

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Successfully Completed Planned Treatment

  Evaluated as the successful completion of at least 5 weekly cisplatin or 2 high dose cisplatin without any extended treatment related delays more than 7 days. Overall successful completion is defined as completion by at least 75% of patients.

  Up to 7 weeks

Secondary Outcomes (4)

• Proportion of Participants With Reported High Grade Ototoxicity

  Up to 18 weeks

• Number of Participants Reporting Tinnitus by Severity

  Up to 18 weeks

• Percentage of Participants Reporting Sodium Thiosulfate (STS)-Specific Symptomology

  Up to 18 weeks

• Frequency of Hearing Handicap

  Up to 18 weeks

Study Arms (1)

Cisplatin, Radiotherapy, STS

EXPERIMENTAL

Patients undergo standard of care radiation therapy daily in combination with cisplatin on day 1. Between 4-5 hours after each cisplatin infusion, patients also receive sodium thiosulfate over 1-2 hours on day 1. Treatment will continue on either a 1 week or 3 week cycle per physician discretion for up to 6-7 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Cisplatin; Other: Hearing Handicap Inventory for Adults - Screening; Radiation: Radiation Therapy; Drug: Sodium Thiosulfate

Interventions

Cisplatin DRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, Lederplatin, Metaplatin, Neoplatin, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platiran, Platistin, Platosin

Cisplatin, Radiotherapy, STS

Hearing Handicap Inventory for Adults - Screening OTHER

Patient self-assessment questionnaire to measure probability of hearing impairment

Cisplatin, Radiotherapy, STS

Radiation Therapy RADIATION

Radiation therapy will be delivered according to the standard of care

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, Not otherwise specified (NOS), Radiotherapeutics, Radiotherapy, RT

Cisplatin, Radiotherapy, STS

Sodium Thiosulfate DRUG

Given IV

Also known as: Cyanide Antidote Package, Disodium Thiosulfate, S-Hydril, Sodium Hyposulfate, Sodium Thiosulfate Pentahydrate, Sodium Thiosulphate, Sodothiol, Thiosulfate, Sodium, Pentahydrate, Thiosulfuric Acid Disodium Salt

Cisplatin, Radiotherapy, STS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Age \>=18 years
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 50%)
• Demonstrates adequate organ function as defined below:
• 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

You may not qualify if:

• 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
• Has profound hearing impairment at baseline and cannot hear a sound below 90 decibels (dB)
• 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

Sponsors & Collaborators

• Hyunseok Kang, MD: lead
• NRG Oncology: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Oropharyngeal Neoplasms; Hypopharyngeal Neoplasms; Laryngeal Neoplasms; Mouth Neoplasms; Carcinoma

Interventions

Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Radiotherapy; Radiation; sodium thiosulfate

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Laryngeal Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms; Mouth Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Therapeutics; Physical Phenomena

Results Point of Contact

• Title: Dr. Hyunseok Kang, MD
• Organization: University of California, San Francisco

hyunseok.kang@ucsf.edu

(888) 689-8273

Study Officials

• Hyunseok Kang, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 1, 2020
• First Posted: September 9, 2020
• Study Start: October 14, 2020
• Primary Completion: May 31, 2023
• Study Completion: May 31, 2023
• Last Updated: June 28, 2024
• Results First Posted: June 28, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)