AREN0533: Treatment of Newly Diagnosed Higher Risk Favorable Histology Wilms Tumors
All subjects who enroll on this study will start treatment with standard therapy Regimen DD4A. After about 6 weeks of therapy, subjects will have scans done to see how their tumors have reacted to the therapy. Subjects who only had tumors that spread to the lung(s), and whose lung tumors disappear after six weeks of standard therapy, will continue with the standard therapy (Regimen DD4A). However, these subjects will not get any radiation therapy. This is experimental therapy, since these subjects would commonly be given radiation therapy. Subjects who had tumors that spread to other places (or to the lungs and other places), and those with only lung tumors that did not disappear after 6 weeks of standard therapy, will get a new experimental treatment called Regimen M. Subjects who switch from study AREN0532 because they have a genetic change called loss of heterozygosity (LOH) will also get Regimen M therapy. Regimen M has two extra common chemotherapy drugs in it; the subject would not get these drugs on standard treatment. Subjects on Regimen M will also get standard radiation therapy.
Subjects who did not have surgery at diagnosis will have surgery after 6 (or 12) weeks of treatment. Those who have cancer cells that divide rapidly and do not look like normal cells (this is called anaplasia) will not stay on this study. They can enroll on another COG study, AREN0321, or they can discuss other treatment options with their doctor.
-Patients must be less than 30 years of age at the time of diagnosis.
-Prior to enrollment on AREN0533, all patients must have been enrolled on AREN03B2 for central pathology review. Stage III patients with LOH transferring from AREN0532 may be enrolled on this study. Eligible patients for AREN0533 must be:
a) Newly diagnosed Stage IV favorable histology Wilms tumor with or without LOH 1p and 16q or
b) Newly diagnosed Stage III favorable histology Wilms tumor with LOH for 1p and 16q transferring from AREN0532.
-Patients with bilateral Wilms tumors (Stage V) are not eligible for AREN0533 and should be directed to AREN0534.
-Specimens/materials per Section 5.1 of AREN03B2 should be submitted for central review by Day 7.
-Timing considerations: Patients must begin protocol therapy on AREN0533 by Day 14 after surgery or biopsy, unless medically contraindicated. It is suggested that samples and studies be submitted by Day 7 to allow adequate time for central review to be completed. Patients may begin protocol therapy before central review is completed if medically indicated (e.g., significant symptoms from large tumor burden). However, enrollment on AREN0533 must occur within 7 days after beginning treatment or by Day 14 after surgery or biopsy, whichever comes first. If treatment begins before central review is completed, samples and studies must be submitted immediately to allow central review to be completed.
-The Karnofsky performance status must be 50 for patients > 16 years of age and the Lansky performance status must be 50 for patients <= 16 years of age.
-Patients cannot have had prior tumor-directed chemotherapy or radiotherapy except for patients transferring from AREN0532 or those treated for emergent issues, as medically indicated.
-Adequate liver function defined as:
*Total bilirubin 1.5 x upper limit of normal (ULN) for age, and
*SGOT (AST) or SGPT (ALT) < 2.5 x upper limit of normal (ULN) for age.
-Adequate cardiac function defined as:
*Shortening fraction of 27% by echocardiogram, or
*Ejection fraction of 50% by radionuclide angiogram.
-Female patients of childbearing age must have a negative pregnancy test.
-Female patients who are lactating must agree to stop breast-feeding.
-Sexually active patients of childbearing potential must agree to use effective contraception.