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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether sodium thiosulfate and mannitol can protect against hearing loss caused by cisplatin chemotherapy. Cisplatin, a common cancer treatment, can damage the inner ear and lead to hearing problems. Sodium thiosulfate, a protective agent, might shield ear cells, while mannitol, a diuretic, could enhance its effectiveness. Individuals currently undergoing cisplatin chemotherapy who have not experienced major hearing issues may be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that sodium thiosulfate and mannitol are generally safe and work well together. Studies have found that sodium thiosulfate can help prevent hearing loss caused by cisplatin chemotherapy and is safe for both children and adults. Most side effects are mild and relate to the method of administration.

Previous patients have used these treatments without major problems, indicating general safety. However, since this trial is in an early stage, researchers are still closely examining the safety and effectiveness of these drugs. Participants should consider this when deciding to join the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Sodium Thiosulfate and Mannitol for chemotherapy-induced hearing loss because these treatments aim to protect hearing without interfering with the effectiveness of chemotherapy. Typically, hearing loss from cisplatin, a common chemotherapy drug, is managed by reducing the dosage, which can compromise cancer treatment. Sodium Thiosulfate works differently by neutralizing harmful byproducts of cisplatin that damage the ear, while Mannitol helps distribute the protective agent more effectively. This unique combination could offer a way to preserve hearing without altering cancer treatment regimens.

What evidence suggests that sodium thiosulfate and mannitol could be effective for chemotherapy-induced hearing loss?

Research has shown that sodium thiosulfate can help prevent hearing loss caused by the chemotherapy drug cisplatin. Among children treated with cisplatin, 50% to 70% experience hearing loss, but sodium thiosulfate significantly reduces this risk. In this trial, one group of participants will receive sodium thiosulfate with mannitol, which helps sodium thiosulfate reach the inner ear, potentially increasing its effectiveness. Together, these two drugs protect the inner ear cells from damage. This method has already led to the approval of sodium thiosulfate for reducing hearing loss in children receiving cisplatin. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT05129748?term=mannitol&draw=2&rank=2

Efficacy of Sodium Thiosulfate and Mannitol in Reducing ... This study aims to assess the efficacy of sodium thiosulfate and mannitol to reduce the hearing impairment caused by cisplatin chemotherapy. Detailed ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11191063/

Use of Sodium Thiosulfate as an Otoprotectant in Patients ... Hearing loss occurs in 50%-70% of children treated with cisplatin. Scientific efforts have led to the recent approval of a pediatric formula ...

3. trialx.com trialx.com/clinical-trials/listings/261050/efficacy-of-sodium-thiosulfate-and-mannitol-in-reducing-ototoxicity-in-adult-patients-receiving-cisplatin-chemotherapy/

Efficacy of Sodium Thiosulfate and Mannitol in Reducing ... This study aims to assess the efficacy of sodium thiosulfate and mannitol to reduce the hearing impairment caused by cisplatin chemotherapy.

4. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-sodium-thiosulfate-reduce-risk-ototoxicity-associated-cisplatin-pediatric-patients

FDA approves sodium thiosulfate to reduce the risk of ... The primary outcome was the percentage of patients with Brock Grade ≥1 hearing loss, assessed using pure tone audiometry after treatment or at ...

5. withpower.com withpower.com/trial/phase-3-hearing-loss-2022-2d377

Sodium Thiosulfate + Mannitol for Chemotherapy-Induced ... Research shows that sodium thiosulfate can help prevent hearing loss caused by the chemotherapy drug cisplatin, especially in children with localized cancer. It ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2772610X24000710

Local application of sodium thiosulfate as an otoprotectant ... However, cisplatin-induced hearing loss (CIHL) is a frequently observed side effect of treatment, most commonly in children but also in adolescents and adults.