Sodium Thiosulfate + Mannitol for Chemotherapy-Induced Hearing Loss

Overseen By Yasmeen Aboulhawa

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sunnybrook Health Sciences Centre

Must be taking: Cisplatin

Disqualifiers: Severe hearing loss, Meniere's, abnormal renal, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 2 months

92 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What evidence supports the effectiveness of the drug sodium thiosulfate for preventing chemotherapy-induced hearing loss?

Research shows that sodium thiosulfate can help prevent hearing loss caused by the chemotherapy drug cisplatin, especially in children with localized cancer. It works by neutralizing harmful effects of cisplatin without affecting its ability to fight cancer. ^{1 2 3 4 5}

Is Sodium Thiosulfate safe for humans?

Sodium Thiosulfate has been studied for its ability to reduce hearing loss caused by the chemotherapy drug cisplatin. It has been shown to be safe and well-tolerated in both children and adults, with most side effects being mild and related to the method of administration. It has received approval in the USA for use in children to prevent hearing loss from cisplatin. ^{1 2 4 6 7}

How does the drug sodium thiosulfate differ from other treatments for chemotherapy-induced hearing loss?

Sodium thiosulfate is unique because it acts as an antioxidant that directly interacts with cisplatin, a chemotherapy drug, to form inactive compounds, reducing the risk of hearing loss without affecting the cancer-fighting ability of cisplatin. It is specifically approved for use in children with localized, non-metastatic tumors, making it a targeted option for pediatric patients. ^{1 2 3 4 5}

Eligibility Criteria

Adults over 18 receiving cisplatin chemotherapy can join this trial if they're willing to consent and use contraception. They must have normal hearing, good overall health (ECOG 0-2), and proper kidney and liver function. Pregnant women or those with severe hearing loss, Meniere's disease, fluctuating or asymmetrical hearing loss are excluded.

Inclusion Criteria

Willing to provide informed consent

I am currently receiving cisplatin as part of my cancer treatment.

I can take care of myself and perform daily activities.

Exclusion Criteria

I have severe hearing loss confirmed by a hearing test.

My liver tests are much higher than normal, indicating liver issues.

Patient unable to follow the protocol for any reason

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pilot Feasibility Study

Participants are recruited into a 2-year pilot feasibility study to evaluate treatment outcomes, adverse events, and logistics of treatment delivery.

2 years

Treatment

Participants receive cisplatin-based chemotherapy with or without sodium thiosulfate and mannitol. Experimental drugs are administered 4-8 hours post-chemotherapy.

2 months

Follow-up

Participants undergo follow-up hearing tests and are monitored for renal function, disease-free survival, and overall survival.

12 months

Treatment Details

Interventions

• Mannitol
• Sodium Thiosulfate

Trial Overview The trial is testing whether Sodium Thiosulfate plus Mannitol can prevent hearing damage in adults undergoing cisplatin chemotherapy. The study will assess the effectiveness of these drugs in protecting inner ear cells from the ototoxic effects of chemotherapy.

Participant Groups

Group I: Standard Cisplatin-based Chemotherapy + Sodium Thiosulfate + Mannitol Experimental Treatment 1 Intervention

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.

Group II: Standard Cisplatin-based Chemotherapy Active Control 1 Intervention

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

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Findings from Research

In a phase 3 trial involving 125 children and adolescents undergoing cisplatin chemotherapy, sodium thiosulfate significantly reduced the incidence of hearing loss, with only 28.6% of participants in the sodium thiosulfate group experiencing hearing loss compared to 56.4% in the control group.

Sodium thiosulfate was found to be safe, with no serious adverse events attributed to its use, suggesting it could be a valuable protective treatment against cisplatin-induced hearing loss in pediatric cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of sodium thiosulfate versus observation on development of cisplatin-induced hearing loss in children with cancer (ACCL0431): a multicentre, randomised, controlled, open-label, phase 3 trial. Freyer, DR., Chen, L., Krailo, MD., et al.[2022]

Sodium thiosulfate (Pedmark®) has been approved in the USA as a chemoprotectant to reduce the risk of hearing loss in pediatric patients receiving cisplatin chemotherapy, specifically for those aged 1 month and older with localized, non-metastatic solid tumors.

The mechanism of action involves sodium thiosulfate interacting with cisplatin to form inactive compounds and enhancing cellular antioxidant defenses, which helps prevent ototoxicity associated with the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium Thiosulfate: Pediatric First Approval. Dhillon, S.[2023]

Sodium thiosulfate has shown efficacy in protecting hearing in pediatric patients undergoing treatment with cisplatin, although its impact on overall survival varies depending on the disease stage, as seen in the ACCL0431 trial.

Previous systemic drugs like amifostine and disulfiram did not demonstrate hearing preservation, highlighting the need for future studies to focus on better-designed trials with larger sample sizes and standardized ototoxicity endpoints.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interventions for cisplatin-induced hearing loss in children and adolescents with cancer. Freyer, DR., Brock, P., Knight, K., et al.[2023]

Trans-tympanic injections of sodium thiosulfate (STS) gel were found to be safe for the middle and inner ears in patients undergoing cisplatin treatment for cancer, with no significant adverse effects reported.

While the average hearing loss was slightly less in treated ears compared to control ears (1.3 dB), the difference was not statistically significant, indicating that further research is needed to enhance the efficacy of STS in preventing cisplatin-induced hearing loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial to test the efficacy of trans-tympanic injections of a sodium thiosulfate gel to prevent cisplatin-induced ototoxicity in patients with head and neck cancer. Rolland, V., Meyer, F., Guitton, MJ., et al.[2022]

Thiosulfate, delivered via a high viscosity formulation of sodium hyaluronan (HYA gel) to the middle ear, effectively protects against cisplatin-induced hair cell loss in a guinea pig model, indicating its potential as a protective treatment for ototoxicity.

The study demonstrated that HYA gel allows for high concentrations of thiosulfate in the cochlea while keeping blood levels low, suggesting a targeted approach that minimizes systemic exposure and maintains the effectiveness of cisplatin as an anti-cancer drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of cisplatin-induced hearing loss by administration of a thiosulfate-containing gel to the middle ear in a guinea pig model. Berglin, CE., Pierre, PV., Bramer, T., et al.[2022]

Sodium thiosulfate (STS) and diethyldithiocarbamate (DDTC) were found to significantly protect against cisplatin-induced ototoxicity in hamsters, with STS providing the greatest auditory protection.

Both STS and DDTC not only reduced ototoxicity but also improved survival rates in the hamsters, indicating their potential as protective agents during cisplatin chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The comparative effects of sodium thiosulfate, diethyldithiocarbamate, fosfomycin and WR-2721 on ameliorating cisplatin-induced ototoxicity. Church, MW., Kaltenbach, JA., Blakley, BW., et al.[2019]

DB-020, a novel formulation of sodium thiosulfate, was shown to be safe and well tolerated in a phase 1a study with healthy volunteers, indicating its potential for protecting against cisplatin-induced hearing loss without compromising the chemotherapy's effectiveness.

The study demonstrated that intratympanic administration of DB-020 resulted in minimal systemic absorption of thiosulfate, suggesting it can deliver high concentrations directly to the cochlea, which may help prevent ototoxicity associated with cisplatin treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study to evaluate safety, tolerability and pharmacokinetics of a novel intra-tympanic administered thiosulfate to prevent cisplatin-induced hearing loss in cancer patients. Viglietta, V., Shi, F., Hu, QY., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Effects of sodium thiosulfate versus observation on development of cisplatin-induced hearing loss in children with cancer (ACCL0431): a multicentre, randomised, controlled, open-label, phase 3 trial. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Sodium Thiosulfate: Pediatric First Approval. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Interventions for cisplatin-induced hearing loss in children and adolescents with cancer. [2023]

4. England pubmed.ncbi.nlm.nih.gov

A randomized controlled trial to test the efficacy of trans-tympanic injections of a sodium thiosulfate gel to prevent cisplatin-induced ototoxicity in patients with head and neck cancer. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Prevention of cisplatin-induced hearing loss by administration of a thiosulfate-containing gel to the middle ear in a guinea pig model. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

The comparative effects of sodium thiosulfate, diethyldithiocarbamate, fosfomycin and WR-2721 on ameliorating cisplatin-induced ototoxicity. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Phase 1 study to evaluate safety, tolerability and pharmacokinetics of a novel intra-tympanic administered thiosulfate to prevent cisplatin-induced hearing loss in cancer patients. [2021]