CHILDREN#S ONCOLOGY GROUP AREN2231 02/20/2025 Risk Adapted Treatment of Unilateral Favorable Histology Wilms Tumors (FHWT) A COG Groupwide Phase 3 Study Study Exempt from IND Requirements per 21 CFR 312.2(b)

ABSTRACT This phase Ill trial studies using risk factors in determining treatment for children with favorable tissue (histology) Wilms tumors (FHWT). Wilms Tumor is the most common type of kidney cancer in children, and FHWT is the most common subtype. Previous large clinical trials have established treatment plans that are likely to cure most children with FHWT, however some children still have their cancer come back (called relapse) and not all survive. Previous research has identified features of FHWT that are associated with higher or lower risks of relapse. The term "risk" refers to the chance of the cancer coming back after treatment. Using results of tumor histology tests, biology tests, and response to therapy may be able to improve treatment for children with FHWT.