This trial will assess the effect of STS in preventing subsequent hearing loss when patients are re-challenged with cisplatin therapy at relapse/progression, as well as the efficacy of cisplatin/STS or cisplatin/STS/SAHA for patients with relapsed hepatoblastoma, Wilms, Germ Cell Tumor (GCT) and Neuroblastoma stratified by initial cisplatin sensitivity. Important pharmacokinetic measurements focused on cisplatin and STS in children, with varying degrees of renal function, will be assessed. Such pharmacokinetic data will fill a current gap in our clinical knowledge base and enable safer use of such agents for all children with such cancers, regardless of kidney function, in the future.
CSS-JG-2201: Cisplatin and Sodium Thiosulfate Otoprotection With or Without SAHA/Vorinostat Histone Deacetylase Inhibition for Relapsed/Refractory Hepatoblastoma and Other Embryonal Tumors.
Inclusion Criteria:
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
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
1. Adequate Bone Marrow Function Defined as:
a.Peripheral absolute neutrophil count (ANC) greater than or equal to 750/uL
b.Platelet count greater than or equal to 75,000/uL (transfusion independent defined as no platelet transfusions within 7 days)
c.Hemoglobin greater than or equal to 8.0 g/dL (may receive red blood cell transfusions)
2.Adequate Liver Function Defined As:
a.Total OR direct bilirubin less than or equal to 1.5 x upper limit of normal (ULN) for age, and
b.Aspartate aminotransferase (AST) or Alanine transaminase (ALT) < 10x ULN
3.Adequate Renal Function Defined As:
a.Creatinine clearance or radioisotope glomerular filtration rate (GFR) > 30 mL/min/1.73 m2
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:
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