Sodium Thiosulfate for Hearing Loss in Medulloblastoma

Recruiting at 100 trial locations

Overseen By Ralph Salloum, MD

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Children's Oncology Group

Must not be taking: Anticonvulsants, Thiol agents

Disqualifiers: Metastatic disease, Pregnancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 8

225 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding sodium thiosulfate (STS) can prevent hearing loss during standard cancer treatment for medulloblastoma, a type of brain cancer. For patients with average-risk medulloblastoma, it investigates whether STS can reduce hearing loss caused by the chemotherapy drug cisplatin. For those with low-risk medulloblastoma, the trial tests if less intense radiation therapy can be as effective as the standard approach while causing fewer side effects. The trial seeks patients aged 4 to 21 who have been newly diagnosed with medulloblastoma and show no signs of cancer spread. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must not have received any prior radiation therapy or chemotherapy other than surgery and/or corticosteroids.

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

Research shows that sodium thiosulfate (STS) might help reduce hearing loss caused by cisplatin, a chemotherapy drug used to treat medulloblastoma. One study found that patients who received cisplatin followed by STS had a lower risk of hearing loss compared to those who only received cisplatin. However, another study found that STS did not have the same protective effects in adults.

Despite this, early results are promising for younger patients. Researchers are testing STS along with standard treatments like chemotherapy and radiation, which can have side effects. This trial aims to determine if STS can reduce hearing loss without affecting cancer treatment outcomes. Always consult a healthcare professional to understand the potential risks and benefits before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for hearing loss in medulloblastoma patients focus on managing symptoms or delaying progression through chemotherapy and radiation. But sodium thiosulfate is different. Researchers are excited about this treatment because it specifically targets the toxic side effects of chemotherapy drugs that harm hearing. By potentially protecting the inner ear from damage, sodium thiosulfate could preserve hearing without compromising the effectiveness of cancer treatment. This protective mechanism is what sets it apart from the standard care options.

What evidence suggests that sodium thiosulfate could be an effective treatment for hearing loss in medulloblastoma?

Research has shown that sodium thiosulfate (STS) can help prevent hearing loss caused by cisplatin, a chemotherapy drug. One study found that people who took STS after receiving cisplatin were less likely to lose their hearing. This is important because cisplatin can harm patients' hearing. STS works by neutralizing harmful substances created by cisplatin, which may protect the ears. Previous studies with young cancer patients have demonstrated that STS can effectively prevent hearing loss from cisplatin. In this trial, researchers are evaluating STS for its potential to protect hearing in patients with medulloblastoma, without affecting the success of cancer treatment. ^{1 2 4 6 7}

Who Is on the Research Team?

Ralph Salloum

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 3 to 21 with newly diagnosed medulloblastoma, a brain cancer. They must have normal kidney and liver function, no prior tumor-directed therapy except surgery/corticosteroids, and not be pregnant or breastfeeding. Participants need confirmed negative spinal fluid tests for metastasis, controlled seizures if present, and normal hearing in at least one ear.

Inclusion Criteria

All patients and/or their parents or legal guardians must sign a written informed consent

Patient and/or their parents or legal guardians have signed informed consent for APEC14B1 Part A - Eligibility Screening and Molecular Characterization

All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria

I haven't had radiation or chemotherapy, only surgery or steroids.

Patients must not have any known hypersensitivity to STS, sulfates/sulfites, or other thiol agents (e.g., amifostine, n-acetylcysteine, MESNA, and captopril)

I am not pregnant, breastfeeding, and if of childbearing potential, I agree to use effective contraception during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiotherapy

Patients undergo radiation therapy 5 days per week for 6 weeks and receive vincristine intravenously once weekly on weeks 2-7

6 weeks

5 visits per week (in-person)

Maintenance

Patients receive a combination of lomustine, cisplatin, sodium thiosulfate, and cyclophosphamide over multiple cycles, with MRI and CSF collection throughout

Up to 54 weeks

Multiple visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 10 years

Every 3 months for years 1-2, every 6 months for years 3-4, annually for years 5-10

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Lomustine
• Mesna
• Radiation Therapy
• Sodium Thiosulfate
• Vincristine

Trial Overview The study examines whether sodium thiosulfate can reduce cisplatin-induced hearing loss in patients with average-risk medulloblastoma during standard treatment including surgery, chemotherapy (cisplatin), and radiation. It also explores less intense therapy's effectiveness for low-risk patients to minimize side effects.

How Is the Trial Designed?

Group I: Treatment (chemoradiotherapy, maintenance) Experimental Treatment 12 Interventions

See Detailed Description.

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 24 medulloblastoma patients treated with carboplatin instead of cisplatin, 23 patients were alive at the time of assessment, indicating a favorable overall survival rate.

Only 10.5% of patients experienced significant hearing loss, suggesting that carboplatin has a lower risk of ototoxicity compared to traditional cisplatin treatments, especially in younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and ototoxicity: hearing loss rates among survivors of childhood medulloblastoma. Musial-Bright, L., Fengler, R., Henze, G., 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]

The EORTC 1634-BTG/NOA-23 trial aims to improve treatment for post-pubertal medulloblastoma patients by comparing standard-dose versus reduced-dose craniospinal radiotherapy and adding the SMO inhibitor sonidegib to standard therapy, potentially reducing toxicity and enhancing efficacy.

This study will provide valuable long-term data on treatment side effects and quality of life, which is crucial for developing better treatment strategies for this rare brain cancer in adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of Randomized Trials in Adults with Medulloblastoma-The Example of EORTC 1634-BTG/NOA-23. Hau, P., Frappaz, D., Hovey, E., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05382338

NCT05382338 | A Study of Treatment for Medulloblastoma ... This trial tests whether the addition of sodium thiosulfate (STS) to standard of care chemotherapy and radiation therapy reduces hearing loss.

2. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK612653

Anhydrous sodium thiosulfate for preventing hearing loss ... Clinical trial evidence shows that hearing loss is less likely in people having anhydrous sodium thiosulfate after cisplatin.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e15075

Effect of sodium thiosulfate anhydrous on cisplatin-induced ... PEDMARK (Sodium Thiosulfate anhydrous) reduced the risk of CIO cases with non-metastatic solid tumors observed in Phase 3 studies (SIOPEL 6 & ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT00716976

NCT00716976 | Sodium Thiosulfate in Preventing Hearing ... Study Overview. RATIONALE: Sodium thiosulfate may reduce or prevent hearing loss in young patients receiving cisplatin for cancer. It is not yet known whether ...

5. medicine.yale.edu medicine.yale.edu/ycci/clinicaltrials/trial/a-study-of-treatment-for-medulloblastoma-using-sodium-thiosulfate-to-reduce-hearing-loss/

A Phase 3 Study of Sodium Thiosulfate for Reduction of ... Previous studies with STS have shown that it may help reduce or prevent hearing loss caused by cisplatin. In the low-risk medulloblastoma ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/212937Orig1s000AdminCorres.pdf

212937Orig1s000 - accessdata.fda.gov Sodium thiosulfate has not demonstrated the prevention of ototoxicity caused by platinum compounds in the adult population in controlled ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/212937s000lbl.pdf

212937s000lbl.pdf - accessdata.fda.gov Both activities may contribute to the ability of sodium thiosulfate to reduce the risk of ototoxicity. Concurrent incubation of sodium thiosulfate with ...