Preventing hearing loss during cisplatin therapy with Sodium Thiosulfate

Cisplatin and Sodium Thiosulfate Otoprotection With or Without SAHA/Vorinostat Histone Deacetylase Inhibition for Relapsed/Refractory Hepatoblastoma and Other Embryonal Tumors

This study tests if Sodium Thiosulfate can help prevent hearing loss in children receiving cisplatin treatment for certain cancers.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 33 (estimated)
• Ages: 1 Month to 39 Years
• Sex: All
• Sponsor: Children's Hospital Medical Center, Cincinnati (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, Radiation
• Locations: 1 site (Cincinnati, Ohio)
• Trial ID: NCT05756660 on ClinicalTrials.gov

What this trial studies

This trial aims to evaluate the effectiveness of Sodium Thiosulfate (STS) in preventing hearing loss in patients undergoing re-treatment with cisplatin for relapsed or refractory cancers such as hepatoblastoma. Participants will receive either a regimen of Cisplatin and STS or Cisplatin, STS, and Vorinostat/SAHA. The study will also gather important pharmacokinetic data on how these drugs interact in children with varying kidney function. This research seeks to enhance the safety and efficacy of cisplatin therapy in pediatric oncology.

Who should consider this trial

Good fit: Ideal candidates include children and young adults aged 1 month to 39 years with relapsed or refractory hepatoblastoma, Wilms tumor, Germ Cell Tumor, or Neuroblastoma who have previously shown sensitivity or resistance to cisplatin.

Not a fit: Patients who are not eligible include those with a life expectancy of less than 8 weeks or those who do not meet the specific cancer type and treatment response criteria.

Why it matters

Potential benefit: If successful, this study could significantly reduce the incidence of hearing loss in children receiving cisplatin therapy.

How similar studies have performed: While the approach of using Sodium Thiosulfate for otoprotection is promising, it is still considered novel and has not been extensively tested in similar contexts.

Eligibility criteria

Inclusion Criteria:

* Patients must be \> 1 month and ≤ 39 years old at study enrollment
* Histologically proven, at time of diagnosis or relapse:

  1. 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.
  2. 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.
  3. 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:

  1. 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.
  2. Immunotherapy: Must not have received within 2 weeks of entry onto this study.
  3. 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

  1. Adequate Bone Marrow Function Defined as:

     1. Peripheral absolute neutrophil count (ANC) greater than or equal to 750/uL
     2. Platelet count greater than or equal to 75,000/uL (transfusion independent defined as no platelet transfusions within 7 days)
     3. Hemoglobin greater than or equal to 8.0 g/dL (may receive red blood cell transfusions)
  2. Adequate Liver Function Defined As:

     1. Total OR direct bilirubin less than or equal to 1.5 x upper limit of normal (ULN) for age, and
     2. Aspartate aminotransferase (AST) or Alanine transaminase (ALT) \< 10x ULN
  3. Adequate Renal Function Defined As:

     1. Creatinine clearance or radioisotope glomerular filtration rate (GFR) \> 30 mL/min/1.73 m2
* Baseline Audiology Requirements:

  1. Subjects must have a successful audiology examination prior to enrollment. Patients may have Boston grade III or IV hearing loss and still be eligible to enroll as long as they did not receive 3 or more cycles of cisplatin during upfront therapy WITH sodium thiosulfate. There is no specific baseline hearing level/grade requirement beyond that to be eligible, but the baseline level of hearing must be clearly established and recorded

Exclusion Criteria:

* 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:

  1. 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
  2. Lactating females who plan to breastfeed their infants.
  3. 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

Where this trial is running

Cincinnati, Ohio

• Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States (Recruiting)

Study contacts

• Principal investigator: James Geller, MD — Children's Hospital Medical Center, Cincinnati
• Study coordinator: Site Contact Cincinnati Children's Hospital Medical Center

Conditions Ototoxicity, Drug-Induced; Cisplatin; Sodium Thiosulfate; Relapsed/Refractory Hepatoblastoma; PedMark; Embryonal Tumor