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Sodium Thiosulfate for the Prevention of Ototoxicity in Patients With Locally Advanced Squamous Cell Cancer of the Head and Neck Undergoing Chemoradiation With Cisplatin

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ClinicalTrials.gov Identifier: NCT04541355
Recruitment Status : Active, not recruiting
First Posted : September 9, 2020
Last Update Posted : August 5, 2021
Sponsor:
Collaborator:
NRG Oncology
Information provided by (Responsible Party):
Hyunseok Kang, MD, University of California, San Francisco

Tracking Information
First Submitted Date  ICMJE September 1, 2020
First Posted Date  ICMJE September 9, 2020
Last Update Posted Date August 5, 2021
Actual Study Start Date  ICMJE October 14, 2020
Estimated Primary Completion Date March 6, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 1, 2020)
Number of patients who successfully completed planned treatment [ Time Frame: Up to 7 days after the last dose of sodium thiosulfate (STS) ]
Evaluated as the successful completion of 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 in each cohorts.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 1, 2020)
  • Frequency of treatment-related adverse events [ Time Frame: 3 months after completion of chemoradiation ]
    Treatment-related adverse events will be classified using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
  • Incidence of high grade ototoxicity [ Time Frame: 3 months after completion of chemoradiation ]
    Defined by change of grade >= 2 based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (for patients on a monitoring program with audiogram in each cohort. Will report the proportion of patients experiencing high-grade toxicity with exact binomial 95% confidence intervals.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sodium Thiosulfate for the Prevention of Ototoxicity in Patients With Locally Advanced Squamous Cell Cancer of the Head and Neck Undergoing Chemoradiation With Cisplatin
Official Title  ICMJE A Phase II Study of Sodium Thiosulfate (STS) for Prevention of Ototoxicity in Patients With Locally Advanced Squamous Cell Carcinoma of Head and Neck (SCCHN) Undergoing Concurrent Chemoradiation With Cisplatin
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.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Drug: Cisplatin
    Given IV
    Other Names:
    • Abiplatin
    • Blastolem
    • Briplatin
    • CDDP
    • Cis-diammine-dichloroplatinum
    • Cis-diamminedichloridoplatinum
    • 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
    • DDP
    • Lederplatin
    • Metaplatin
    • Neoplatin
    • Peyrone''s Chloride
    • Peyrone''s Salt
    • Placis
    • Plastistil
    • Platamine
    • Platiblastin
    • Platiblastin-S
    • Platinex
    • Platinol
    • Platinol- AQ
    • Platinol-AQ
    • Platinol-AQ VHA Plus
    • Platinoxan
    • Platinum
    • Platinum Diamminodichloride
    • Platiran
    • Platistin
    • Platosin
  • Other: Hearing Handicap Inventory for Adults - Screening
    Patient self-assessment questionnaire to measure probability of hearing impairment
  • Radiation: Radiation Therapy
    Radiation therapy will be delivered according to the standard of care
    Other Names:
    • Cancer Radiotherapy
    • Irradiate
    • Irradiated
    • Irradiation
    • Radiation
    • Radiation Therapy, Not otherwise specified (NOS)
    • Radiotherapeutics
    • Radiotherapy
    • RT
  • Drug: Sodium Thiosulfate
    Given IV
    Other Names:
    • Cyanide Antidote Package
    • Disodium Thiosulfate
    • S-Hydril
    • Sodium Hyposulfate
    • Sodium Thiosulfate Pentahydrate
    • Sodium Thiosulphate
    • Sodothiol
    • Thiosulfate, Sodium, Pentahydrate
    • Thiosulfuric Acid Disodium Salt
  • Diagnostic Test: Questionnaire based on Patient Reported Outcomes-Criteria for Adverse Events (PRO-CTCAE) (PRO-CTCAE)
    Selected oral, GI, neurologic and perceptual symptoms are reported by patient
Study Arms  ICMJE
  • Experimental: Cohort A: Weekly Cisplatin + STS
    Patients undergo standard of care radiation therapy daily for 6-7 weeks. Patients receive 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 7 days for up to 7 cycles in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Cisplatin
    • Other: Hearing Handicap Inventory for Adults - Screening
    • Radiation: Radiation Therapy
    • Drug: Sodium Thiosulfate
    • Diagnostic Test: Questionnaire based on Patient Reported Outcomes-Criteria for Adverse Events (PRO-CTCAE) (PRO-CTCAE)
  • Experimental: Cohort B: High Dose Cisplatin + STS
    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.
    Interventions:
    • Drug: Cisplatin
    • Other: Hearing Handicap Inventory for Adults - Screening
    • Radiation: Radiation Therapy
    • Drug: Sodium Thiosulfate
    • Diagnostic Test: Questionnaire based on Patient Reported Outcomes-Criteria for Adverse Events (PRO-CTCAE) (PRO-CTCAE)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 4, 2021)
3
Original Estimated Enrollment  ICMJE
 (submitted: September 1, 2020)
16
Estimated Study Completion Date  ICMJE March 6, 2024
Estimated Primary Completion Date March 6, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. 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
  2. Participants must be eligible for cisplatin-based concurrent chemotherapy in conjunction with at least 6 weeks of daily fractionated radiation therapy
  3. Age >=18 years
  4. Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 50%)
  5. Demonstrates adequate organ function as defined below:

    1. Absolute neutrophil count >= 1,000/microliter (mcL)
    2. Platelets >= 100,000/mcL
    3. Total bilirubin within normal institutional limits, unless elevated due to Gilbert's syndrome and direct bilirubin is within normal limits
    4. Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase (SGOT)) =< 3 X institutional upper limit of normal
    5. Alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase (SGPT)) =< 3 X institutional upper limit of normal
    6. 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
  6. Ability to understand a written informed consent document, and the willingness to sign it
  7. 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
  8. 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

Exclusion Criteria:

  1. Participants that are not eligible for cisplatin-based chemoradiation for reasons such as chronic kidney disease, severe hearing loss, and severe peripheral neuropathy
  2. Uncontrolled inter-current illness or psychiatric illness/social situation that would limit compliance with study requirements
  3. Has known hypersensitivity to cisplatin, sodium thiosulfate or any of its excipients
  4. Has profound hearing impairment at baseline and cannot hear a sound below 90 decibels (dB)
  5. Participants with uncompensated congestive heart failure New York Heart Association (NYHA) class 3 or above
  6. 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
  7. 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04541355
Other Study ID Numbers  ICMJE 20208
NCI-2020-05752 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Hyunseok Kang, MD, University of California, San Francisco
Study Sponsor  ICMJE Hyunseok Kang, MD
Collaborators  ICMJE NRG Oncology
Investigators  ICMJE
Principal Investigator: Hyunseok Kang, MD University of California, San Francisco
PRS Account University of California, San Francisco
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP