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

Primary Purpose

Ototoxic Hearing Loss

Status
Recruiting
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Sodium Thiosulfate + Mannitol
Sponsored by
Sunnybrook Health Sciences Centre
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Ototoxic Hearing Loss focused on measuring Hearing Loss, Deafness, Cisplatin-induced Ototoxicity, Sensorineural hearing loss, Ear diseases, Sodium Thiosulfate

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Sunnybrook Health Sciences CentreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Standard Cisplatin-based Chemotherapy + Sodium Thiosulfate + Mannitol

Standard Cisplatin-based Chemotherapy

Arm Description

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.

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

To monitor potential oncological impact of sodium thiosulfate and mannitol on long-term renal clearance
Participants will be monitored for renal function via serum creatinine (umol/L) and creatinine clearance (ml/min).
To monitor potential oncological impact of sodium thiosulfate and mannitol on disease free survival
Participants will be monitored for disease free survival via cancer staging details and clinical prognosis
To monitor potential oncological impact of sodium thiosulfate and mannitol on overall survival
Participants will be monitored for overall survival via time in months
To assess the short and long-term adverse event reporting from combination of sodium thiosulfate, mannitol and cisplatin.
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

Full Information

First Posted
November 3, 2021
Last Updated
April 12, 2023
Sponsor
Sunnybrook Health Sciences Centre
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1. Study Identification

Unique Protocol Identification Number
NCT05129748
Brief Title
Efficacy of Sodium Thiosulfate and Mannitol in Reducing Ototoxicity in Adult Patients Receiving Cisplatin Chemotherapy
Official Title
A Multicenter Randomized Phase II Clinical Trial of the Efficacy of Sodium Thiosulfate and Mannitol in Reducing Ototoxicity in Adult Patients Receiving Cisplatin Chemotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 15, 2023 (Actual)
Primary Completion Date
January 2027 (Anticipated)
Study Completion Date
December 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sunnybrook Health Sciences Centre

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ototoxic Hearing Loss
Keywords
Hearing Loss, Deafness, Cisplatin-induced Ototoxicity, Sensorineural hearing loss, Ear diseases, Sodium Thiosulfate

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
1:1 randomization between cisplatin alone, and cisplatin, sodium thiosulfate and mannitol.
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
92 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Standard Cisplatin-based Chemotherapy + Sodium Thiosulfate + Mannitol
Arm Type
Experimental
Arm Description
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.
Arm Title
Standard Cisplatin-based Chemotherapy
Arm Type
No Intervention
Arm Description
Participants will receive the standard of care (cisplatin-based chemotherapy) only.
Intervention Type
Drug
Intervention Name(s)
Sodium Thiosulfate + Mannitol
Intervention Description
Drug delivery will be sequential, where Mannitol will be infused over 30 minutes and Sodium Thiosulfate will be infused over 15 minutes.
Primary Outcome Measure Information:
Title
Improvement in hearing threshold with sodium thiosulfate and mannitol administration
Description
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.
Time Frame
2 months
Secondary Outcome Measure Information:
Title
To monitor potential oncological impact of sodium thiosulfate and mannitol on long-term renal clearance
Description
Participants will be monitored for renal function via serum creatinine (umol/L) and creatinine clearance (ml/min).
Time Frame
12 months
Title
To monitor potential oncological impact of sodium thiosulfate and mannitol on disease free survival
Description
Participants will be monitored for disease free survival via cancer staging details and clinical prognosis
Time Frame
12 months
Title
To monitor potential oncological impact of sodium thiosulfate and mannitol on overall survival
Description
Participants will be monitored for overall survival via time in months
Time Frame
12 months
Title
To assess the short and long-term adverse event reporting from combination of sodium thiosulfate, mannitol and cisplatin.
Description
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
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yasmeen Aboulhawa
Phone
1-416-480-6100
Ext
85392
Email
yasmeen.aboulhawa@sri.utoronto.ca
Facility Information:
Facility Name
Sunnybrook Health Sciences Centre
City
Toronto
State/Province
Ontario
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yasmeen Aboulhawa
Email
yasmeen.aboulhawa@sri.utoronto.ca
First Name & Middle Initial & Last Name & Degree
Trung Le

12. IPD Sharing Statement

Plan to Share IPD
No

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

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