Sodium Thiosulfate Otoprotection During Salvage Cisplatin Therapy

NCT05756660 | Suspended Early Phase 1 DMC FDA Drug

• 1 other identifier: CSS-JG-2201
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This study will attempt to demonstrate the efficacy of Sodium Thiosulfate (STS) in preventing hearing loss in patients re-treated with cisplatin-based therapy according to regimens Cisplatin and STS (regimen CS) and Cisplatin, STS and Vorinostat/SAHA (regimen CSS).

Conditions

Ototoxicity, Drug-Induced

Keywords

Cisplatin; Sodium Thiosulfate; Relapsed/Refractory Hepatoblastoma; PedMark; Embryonal Tumor

Outcome Measures

Primary Outcomes (1)

• Prevention of hearing loss

  To demonstrate the efficacy of Sodium Thiosulfate (STS) in preventing hearing loss in patients re-treated with cisplatin-based therapy according to regimens Cisplatin/STS (CS) and Cisplatin/STS/SAHA (CSS)

  Through study completion up to 5 years

Secondary Outcomes (5)

• Prevention of hearing loss and tumor reduction

  Through study completion up to 5 years

• Number of Participants with Treatment-Related Adverse Events

  Through study completion up to 5 years

• Stratum 1 efficacy

  Through study completion up to 5 years

• Stratum 2 efficacy

  Through study completion up to 5 years

• Maximum Plasma Concentration [Cmax]

  Through study completion up to 5 years

Study Arms (3)

Stratum 1- Regimen CS

EXPERIMENTAL

Cisplatin sensitive/no progression on cisplatin (when given at first diagnosis)

Drug: Sodium Thiosulfate

Stratum 2A- Regimen CSS

EXPERIMENTAL

Cisplatin resistant or progressed on cisplatin after initial response (when given at first diagnosis)

Drug: Sodium Thiosulfate

Stratum 2B- Regimen CSS

EXPERIMENTAL

Wilms tumor, GCT, Neuroblastoma

Drug: Sodium Thiosulfate

Interventions

Sodium Thiosulfate DRUG

This goal of this study is to evaluate the efficacy of the proposed regimens in patients with relapsed/refractory platinum pre-treated patients with Hepatoblastoma, Wilms tumor, Germ Cell Tumor (GCT), and Neuroblastoma. The patients' initial cisplatin response (hepatoblastoma) and diagnosis will determine their treatment regimen on this study.

Also known as: Cisplatin, Vorinostat/ SAHA

Stratum 1- Regimen CS; Stratum 2A- Regimen CSS; Stratum 2B- Regimen CSS

Eligibility Criteria

• Age: 1 Month - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must be \> 1 month and ≤ 39 years old at study enrollment
• Histologically proven, at time of diagnosis or relapse:
• Stratum 1: Arm CS (Cisplatin/STS): Previously chemosensitive to cisplatin defined as an AFP drop of 1 log (90%) and/or an objective tumor response of 30% or greater on imaging while receiving cisplatin.
• Stratum 2A: Cisplatin/STS/SAHA (CSS): Previously chemosensitive but with noted subsequent progression on cisplatin or initially chemoresistant to cisplatin (all other hepatoblastoma patients). Resistance to cisplatin is defined as rising alpha-fetoprotein (AFP) x 2 consecutive measurements or imaging progression including growth of known lesions or new lesions while patient is receiving a cycle of chemotherapy containing cisplatin or relapse noted within 3 months of last cisplatin administration.
• Stratum 2B: CSS: Relapsed/refractory Wilms tumor, Germ Cell Tumor, or Neuroblastoma
• Patients must have a life expectancy of ≥ 8 weeks.
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study:
• Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry onto this study. Previous SAHA administration is permitted. Tacrolimus and Sirolimus with levels \<= 10 ng/ml are not considered myelosuppressive.
• Immunotherapy: Must not have received within 2 weeks of entry onto this study.
• Radiation therapy (RT): greater than or equal to 2 weeks for local palliative RT (small port); greater than or equal to 6 months must have elapsed if prior craniospinal RT or if greater than or equal to 50% radiation of pelvis
• Patients may not be enrolled on another clinical trial or receiving any other investigational therapies (within 2 weeks prior to study enrollment).
• Organ Function Requirements
• Adequate Bone Marrow Function Defined as:
• Peripheral absolute neutrophil count (ANC) greater than or equal to 750/uL
• Platelet count greater than or equal to 75,000/uL (transfusion independent defined as no platelet transfusions within 7 days)

You may not qualify if:

• Patients with any uncontrolled, intercurrent illness including, but not limited to, uncontrolled infection
• Patients with symptomatic congestive heart failure (defined as Grade 2 or higher heart failure per CTCAE version 5.0)
• Patients with Renal Tubular Acidosis (RTA) as evidenced by serum bicarbonate \< 16 mmol/L and serum phosphate ≤ 2 mg/dL (or \< 0.8 mmol/L) without supplementation. Patients requiring electrolyte supplementation for RTA will be permitted if bicarbonate ≥16 mmol/L and phosphate \> 2mg/dL after at least 7 days of stable supplementation regimen
• Pregnancy and Breastfeeding:
• Female patients who are pregnant or breast-feeding will not be entered in the study. A negative pregnancy test within 72 hours of starting therapy is required for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants.
• Sexually active patients of reproductive potential must agree to use an effective contraceptive method for the duration of their study participation
• Patients on tacrolimus and/or sirolimus with levels of either targeted \> 10 ng/mL
• Known allergy to any component of CS or CSS therapy, as indicated

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related Links

• Cincinnati Children's Hospital Medical Center home page

MeSH Terms

Conditions

Ototoxicity; Hepatoblastoma; Neoplasms, Germ Cell and Embryonal

Interventions

sodium thiosulfate; Cisplatin; Vorinostat

Condition Hierarchy (Ancestors)

Ear Diseases; Otorhinolaryngologic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries; Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Katherine Somers, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Three strata are identified for this study: Stratum 1: Cisplatin sensitive/no progression on cisplatin (when given at first diagnosis): Regimen Cisplatin/STS (CS) Stratum 2A: Cisplatin resistant or progressed on cisplatin after initial response (when given at first diagnosis): Regimen Cisplatin/STS/SAHA (CSS) Stratum 2B: Wilms tumor, Germ Cell tumor, Neuroblastoma: Regimen CSS Within each of the 3 eligible strata, patients will be enrolled and directly assigned to their respective protocol therapy, yielding 3 independent single-arm cohorts. Patients will receive protocol therapy for up to 6 3-week cycles before moving to follow-up.

Study Record Dates

• First Submitted: February 9, 2023
• First Posted: March 6, 2023
• Study Start: March 1, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: October 20, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)