Efficacy of Sodium Thiosulfate and Mannitol in Reducing Ototoxicity in Adult Patients Receiving Cisplatin Chemotherapy

NCT05129748 | Recruiting Phase 2

• 1 other identifier: 1818
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief Summary

One common side effect of cisplatin chemotherapy is ototoxicity. The drugs sodium thiosulfate and mannitol may protect against cisplatin-induced hearing loss. Specifically, sodium thiosulfate has been found to protect the cells in the inner ear, and may therefore prevent hearing loss. Mannitol can help sodium thiosulfate enter the inner ear, and ponteially increase the effectiveness of sodium thiosulfate. This study aims to assess the efficacy of sodium thiosulfate and mannitol to reduce the hearing impairment caused by cisplatin chemotherapy.

Conditions

Ototoxic Hearing Loss

Keywords

Hearing Loss; Deafness; Cisplatin-induced Ototoxicity; Sensorineural hearing loss; Ear diseases; Sodium Thiosulfate

Outcome Measures

Primary Outcomes (1)

• Improvement in hearing threshold with sodium thiosulfate and mannitol administration

  The primary outcome measure of this study will be a comparison of hearing loss between the control and experimental groups. More specifically, each ear will be scored as having hearing loss if there is a greater than 10dB hearing loss in three contiguous frequencies. This will be measured via threshold hearing tests.

  2 months

Secondary Outcomes (4)

• To monitor potential oncological impact of sodium thiosulfate and mannitol on long-term renal clearance

  12 months

• To monitor potential oncological impact of sodium thiosulfate and mannitol on disease free survival

  12 months

• To monitor potential oncological impact of sodium thiosulfate and mannitol on overall survival

  12 months

• To assess the short and long-term adverse event reporting from combination of sodium thiosulfate, mannitol and cisplatin.

  12 months

Study Arms (2)

Standard Cisplatin-based Chemotherapy + Sodium Thiosulfate + Mannitol

EXPERIMENTAL

Participants will receive the standard of care (cisplatin-based chemotherapy) plus the experimental treatment of Sodium Thiosulfate and Mannitol. Both drugs will be administered IV 4 - 8 hours following chemotherapy treatment, as part of post-chemotherapy hydration.

Drug: Sodium Thiosulfate + Mannitol

Standard Cisplatin-based Chemotherapy

NO INTERVENTION

Participants will receive the standard of care (cisplatin-based chemotherapy) only.

Interventions

Sodium Thiosulfate + Mannitol DRUG

Drug delivery will be sequential, where Mannitol will be infused over 30 minutes and Sodium Thiosulfate will be infused over 15 minutes.

Standard Cisplatin-based Chemotherapy + Sodium Thiosulfate + Mannitol

Eligibility Criteria

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

You may qualify if:

• Patients undertaking systemic cisplatin therapy as part of their cancer treatment
• Age ≥ 18
• Willing to provide informed consent
• ECOG performance status 0-2
• For female of child-bearing potential, a negative pregnancy test (beta-HCG) prior to study treatment is required
• Any patient who is of reproductive age should provide written agreement to use adequate contraception for the duration of the trial

You may not qualify if:

• Age less than 18
• Preexisting severe to profound sensorineural hearing loss (unilateral or bilateral) (speech reception threshold \>70dB, or word recognition score \<50%) as confirmed with an audiogram
• History of Meniere's or fluctuating hearing loss
• Asymmetrical hearing loss (bone conduction threshold difference of: (a) 20 dB threshold difference at a single frequency, (b) 15 dB threshold difference at 2 frequencies, (c) 10 dB threshold difference at 3 frequencies
• Abnormal renal function (creatinine clearance \<60 ml/min)
• Abnormal liver function (liver function tests (ALT and ALP) \>2.5 times upper limit of normal without liver metastasis and \>5 times upper limit of normal with liver metastasis
• Previous hypersensitivity to STS or mannitol
• Pregnant and/or nursing women
• Patient unable to follow the protocol for any reason

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

RECRUITING

MeSH Terms

Conditions

Hearing Loss; Deafness; Hearing Loss, Sensorineural; Ear Diseases

Interventions

sodium thiosulfate; Mannitol

Condition Hierarchy (Ancestors)

Hearing Disorders; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates

Central Study Contacts

Yasmeen Aboulhawa

CONTACT

1-416-480-6100; yasmeen.aboulhawa@sri.utoronto.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 1:1 randomization between cisplatin alone, and cisplatin, sodium thiosulfate and mannitol.

Study Record Dates

• First Submitted: November 3, 2021
• First Posted: November 22, 2021
• Study Start: February 15, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 14, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)