AREN1921: Treatment of Newly Diagnosed Diffuse Anaplastic Wilms Tumors (DAWT) and Relapsed Favorable Histology Wilms Tumors (FHWT)

Abstract AREN1921, Treatment of Newly Diagnosed Diffuse Anaplastic Wilms Tumors (DAWT) and Relapsed Favorable Histology Wilms Tumors (FHWT) The outlook for most children with Wilms tumor has improved dramatically due to improved risk stratification and multi-modal therapy, with survival rates currently above 90%. This trial addresses ‘high risk Wilms tumor’ including those with diffuse anaplastic Wilms tumor (DAWT) and those who have relapsed favorable histology Wilms tumor (FHWT). Less than half of patients with Stage 4 DAWT survive (NWTS-5; AREN0321 UH-1/revised UH-1) and the salvage rate for those who relapse is dismal. Given the less than optimal outcome for patients with high risk Wilms tumor (DAWT and relapsed FHWT), this clinical trial aims to improve survival by intensifying treatment. For DAWT, outcomes have ‘improved’ with Regimen UH-1/2 with overall 4-year EFS for Stage 2-4 DAWT now approaching 68%. This trial will expand on the overall improvement observed with the revised UH-1/UH-2 regimen, along with the efficacy signal seen in patients treated with the vincristine/irinotecan (VI) window, using a modification of Regimen UH-1/2 designed to potentially minimize toxicity (Regimen UH-3). The long-term survival for patients with relapsed FHWT remains at approximately 50%. Salvage post- second relapse is achieved in only a small minority of cases. Patients with Standard-Risk relapsed FHWT (2-drug pre-treated FHWT) will receive Regimen UH-3. Salvage rates for patients with High-Risk relapsed FHWT (3-drug pre-treated FHWT) and Very High-Risk relapsed FHWT (≥ 4 drug pre-treated FHWT) will be established in patients treated with cyclophosphamide and topotecan added to an ICE (ifosfamide, carboplatin, etoposide) chemotherapy backbone.