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

Ototoxic Hearing Loss Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05129748
• Other study ID #: 1818
• Status: Recruiting
• Phase: Phase 2
• Start date: February 15, 2023
• Est. completion date: December 2027

Study information

• Verified date: April 2023
• Source: Sunnybrook Health Sciences Centre
• Contact: Yasmeen Aboulhawa
• Phone: 1-416-480-6100
• Email: yasmeen.aboulhawa[@]sri.utoronto.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 92
• Est. completion date: December 2027
• Est. primary completion date: January 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Deafness
• Hearing Loss
• Ototoxic Hearing Loss
• Ototoxicity

Intervention

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.

Locations

Country	Name	City	State
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Sunnybrook Health Sciences Centre

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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).	12 months
Secondary	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	12 months
Secondary	To monitor potential oncological impact of sodium thiosulfate and mannitol on overall survival	Participants will be monitored for overall survival via time in months	12 months
Secondary	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	12 months