Patients must be on aRen03B2 (STu 092010-004).Preoperative chemotherapy:Patients will receive 2 cycles of preoperative chemotherapy over 6 weeks.in BWT patients, in whom all tumors are amenable to partial nephrectomy at Week 6, patient will have surgery and then on to further therapy as determined by the tumors' histology.in BWT patients with a partial response ([GreaterThanorequalTo] 50% reduction in tumor volume) in all lesions at Week 6, but whose tumors are still not amenable to renal sparing surgery, patient will get 6 more weeks of the same chemotherapy (VaD) before second look/definitive surgery at Week 12.in rare situations patients with BWT may have a complete radiographic response to therapy at 6 weeks.in this case, patients will start ee-4a.BWT patients who have [Less Than] 50% response in either kidney at Week 6 will undergo immediate surgery (open biopsy or resection), and proceed with therapy dependent on histology.Some patients with smaller tumors at diagnosis may be amenable to renal sparing surgery even though the response to chemotherapy has been minimal.if the tumors are completely resected by partial nephrectomy, subsequent treatment will be determined by the pathologic findings.other patients may have an asymmetric response.This will result in some patients having renal sparing surgery on one kidney and biopsy only of the contralateral kidney.in these patients, the chemotherapy will be determined by the kidney with highest risk histology.This therapy will continue for 6 more weeks until definitive surgery at Week 12.Management of patients with BWT with varying responses in both kidneys will be individualized.one kidney may be amenable to partial resection and the contralateral unresectable tumor may be found to have high-risk histology.in such a case, one may choose to proceed with nephrectomy of the kidney with high-risk histology rather than intensifying therapy if the majority of one kidney is preserved with partial nephrectomy.Some patients will have a CR with no lesion detectable on imaging after preoperative chemotherapy. This can occur at either 6 weeks or even more rarely at 12 weeks.if there is a complete radiographic response to therapy at 6 weeks, patients should start ee-4a.if there is a complete radiographic response at 12 weeks, patients should start DD-4a.These kidneys will be followed with imaging to detect recurrence.The kidney will be assigned as Stage i.Treatment of the patient will be determined by the highest assigned stage/histology of either kidney.in patients with unilateral tumors who have a PR after 6 weeks of therapy, patients will have renal sparing surgery if feasible.if renal sparing surgery is not feasible, patient will continue with an additional 6 weeks of chemotherapy.Patients who have a less than PR will proceed with nephrectomy at 6 weeks.nephrectomy is also performed if partial nephrectomy is not feasible after 12 weeks of chemotherapy.Based on histology and staging at the time of nephrectomy (at 6 weeks or 12 weeks) the appropriate regimen is followed post nephrectomy.Some patients will have a CR with no lesion detectable on imaging after preoperative chemotherapy.if there is a complete radiographic response to therapy at 6 weeks and the patient is stage i or ii, the patient will continue with ee-4a.Patients who are stage iii or iV will continue with DD-4a.if complete response is noted at 12 weeks and the patient is stage i or ii, the patient will continue with ee-4a.Patients who are stage iii or iV will continue with DD-4a.Patients with DHPLn who develop new renal masses will be treated according to the bilateral schema.The initial chemotherapy regimen for this group of patients, once they have been found to have progression of disease, will be Regimen VaD.Reassessment will occur at 6 weeks to determine if renal sparing surgery is feasible.Subsequent therapy will be dictated by the response to treatment and the pathologic findings after tumor resection.
1. Patients must be < 30 years old at the time of initial diagnosis.
2. Diagnosis: Patients must be previously enrolled on AREN03B2 and confirmed to be eligible for AREN0534. The patient must have one of the following conditions to be eligible for AREN0534: a) Synchronous bilateral Wilms tumors; or b) Unilateral Wilms tumor and aniridia, Beckwith-Wiedemann Syndrome, idiopathic hemihypertrophy, Simpson-Golabi-Behmel-Syndrome, Denys-Drash Syndrome or other associated genitourinary anomalies associated with bilateral Wilms tumor, such as hypospadias and undescended testis (to be eligible, these patients must not undergo any nephrectomy at diagnosis; Note-horseshoe kidney is not associated with bilateral Wilms tumor and these patients should go on the appropriate unilateral Wilms tumor study); or c) Multicentric Wilms tumor (any age) (to be eligible, these patients must no undergo any nephrectomy at diagnosis); or d) Unilateral WT with contralateral nephrogenic rest(s) (any size) in a child under one year of age (to be eligible, these patients must not undergo any nephrectomy at diagnosis) ; or e) Diffuse hyperplastic perilobar nephroblastomatosis (unilateral or bbilateral) defined by central radiological review; or f) Wilms tumor arising in a solitary kidney (patients with metachronous Wilms tumor are not eligible).
* It is often difficult to distinguish Wilms tumors from nephrogenic rests based on imaging studies and percutaneous biopsies. The AREN0534 study uses the guideline that Wilms tumor with a single lesion 1 cm or greater in the contralateral kidney or multiple lesions (of any size) in the contralateral kidney should be treated on the synchronous bilateral Wilms tumor stratum. Patients with an isolated lesion less than 1 cm in the contralateral kidney should be treated on the appropriate study for unilateral Wilms tumor OR on the unilateral Wilms tumor/contralateral nephrogenic rest stratum of this study if they have not undergone nephrectomy and are under one year of age.
Loss of heterozygosity (LOH) results-which are used in the unilateral Wilms tumor studies-are not a requirement for enrollment on AREN0534. Blood samples can be submitted but will not be used to direct AREN0534 therapy.
3. Specimen submission: Specimens/materials per protocol AREN03B2 must be submitted for central review by Day 7. For enrollment on AREN0534, unless a biopsy was done, the submission requirements at enrollment on AREN03B2 refer to imaging studies. Tissue samples are only required if a surgical procedure (biopsy or nephrectomy) was performed at the time of enrollment on AREN03B2.
4. Performance level: 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.
5. Prior therapy: Patients must not have received systemic chemotherapy or radiation therapy prior to treatment on this study.
Patients with unilateral Wilms tumor and aniridia, Beckwith-Wiedemann Syndrome, idiopathic hemihypertrophy, Simpson-Golabi-Behmel-Syndrome, Denys-Drash Syndrome or other associated genitourinary anomalies; or multicentric or unilateral Wilms tumor with contralateral nephrogenic rest(s)(any size) in a child under 1 year of age who undergo a nephrectomy at diagnosis are not eligible for this study (see Section 3.3.2.b above) and should be directed to a unilateral Wilms tumor study.
6. 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.
7. Adequate cardiac function defined as: Shortening fraction of >= 27% by echocardiogram, or Ejection fraction of >= 50% by radionuclide angiogram.
(Cardiac function does not need to be assessed in patients who will not receive doxorubicin as part of their initial therapy on this study [i.e., patients who start on Regimen EE-4A].)
8. Female patients of childbearing age must have a negative pregnancy test. Female patients who are lactating must agree to stop breastfeeding. Sexually active patients of childbearing potential must agree to use effective contraception.
9. All patients and/or their parents or legal guardians must sign a written informed consent.
10. All institutional, FDA, and NCI requirements for human studies must be met.