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

April 12, 2023 updated by: Sunnybrook Health Sciences Centre

A Multicenter Randomized Phase II Clinical Trial of the Efficacy of Sodium Thiosulfate and Mannitol in Reducing Ototoxicity in Adult Patients Receiving Cisplatin Chemotherapy

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Randomized phase II clinical trial: with 1:1 randomization between cisplatin alone, and cisplatin + sodium thiosulfate and mannitol. Participants will first be recruited into a 2-year pilot feasibility study of 24 patients (12 in each arm). The pilot study will be performed to evaluate the feasibility of the trial as defined by the following factors: treatment outcomes, occurrence of adverse events, logistics of treatment delivery, as well as dropout and recruitment rates. The results from the pilot study will support the safety, efficacy, and effectiveness of the sodium thiosuldate and mannitol treatment, confirm feasibility using the factors mentioned above, and serve as an earlier-phase developmental function to enhance the probability of success of the subsequent clinical trial. Participants will complete various pre-treatment hearing tests. Participants will receive sodium thiosulfate and mannitol 4 - 8 hours following chemotherapy treatment. The control group will not receive the experimental intervention. Follow-up hearing tests will be performed at select time intervals following completion of their cancer treatment.

Study Type

Interventional

Enrollment (Anticipated)

92

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Standard Cisplatin-based Chemotherapy + Sodium Thiosulfate + Mannitol
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
Drug delivery will be sequential, where Mannitol will be infused over 30 minutes and Sodium Thiosulfate will be infused over 15 minutes.
No Intervention: Standard Cisplatin-based Chemotherapy
Participants will receive the standard of care (cisplatin-based chemotherapy) only.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improvement in hearing threshold with sodium thiosulfate and mannitol administration
Time Frame: 2 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
To monitor potential oncological impact of sodium thiosulfate and mannitol on long-term renal clearance
Time Frame: 12 months
Participants will be monitored for renal function via serum creatinine (umol/L) and creatinine clearance (ml/min).
12 months
To monitor potential oncological impact of sodium thiosulfate and mannitol on disease free survival
Time Frame: 12 months
Participants will be monitored for disease free survival via cancer staging details and clinical prognosis
12 months
To monitor potential oncological impact of sodium thiosulfate and mannitol on overall survival
Time Frame: 12 months
Participants will be monitored for overall survival via time in months
12 months
To assess the short and long-term adverse event reporting from combination of sodium thiosulfate, mannitol and cisplatin.
Time Frame: 12 months
To determine the causality of adverse events and serious adverse events and grading according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v.5.0
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sunnybrook Health Sciences Centre

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 15, 2023

Primary Completion (Anticipated)

January 1, 2027

Study Completion (Anticipated)

December 1, 2027

Study Registration Dates

First Submitted

November 3, 2021

First Submitted That Met QC Criteria

November 18, 2021

First Posted (Actual)

November 22, 2021

Study Record Updates

Last Update Posted (Actual)

April 14, 2023

Last Update Submitted That Met QC Criteria

April 12, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1818

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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