Treatment for Patients With Bilateral, Multicentric, or Bilaterally-Predisposed Unilateral Wilms Tumor

Location:

Rochester, Minn.

Trial status:

Open for Enrollment

Why is this study being done?

OBJECTIVES: I. To improve 4-year event-free survival (EFS) to 73% for young patients with bilateral Wilms tumor (BWT). II. To prevent complete removal of at least one kidney in 50% of patients with BWT by using prenephrectomy 3-drug chemotherapy induction with vincristine (vincristine sulfate), dactinomycin, and doxorubicin (doxorubicin hydrochloride). III. To evaluate the efficacy of chemotherapy in preserving renal units in children with diffuse hyperplastic perilobar nephroblastomatosis (DHPLN) and preventing Wilms tumor development. IV. To facilitate partial nephrectomy in lieu of nephrectomy in 25% of children with unilateral tumors and aniridia, Beckwith-Wiedemann syndrome (BWS), hemihypertrophy or other overgrowth syndromes, by using prenephrectomy 2-drug chemotherapy induction with vincristine and dactinomycin. V. To have 75% of patients with BWT undergo definitive surgical treatment by 12 weeks after initiation of chemotherapy. OUTLINE: PREOPERATIVE CHEMOTHERAPY: Patients receive preoperative chemotherapy based on radiographic stage in most cases and if a biopsy was performed then based on histology. VAD REGIMEN (stage I-IV bilateral Wilms tumor [BWT] with biopsy revealing favorable histology or no preoperative biopsy; stage I-III BWT with focal anaplasia; stage I BWT with diffuse anaplasia; or high-risk, stage III-IV unilateral Wilms tumor [WT] with contralateral nephrogenic rest [NR] or predisposition syndrome): Patients receive vincristine sulfate IV on days 1, 8, 15, 22, 29, and 36 (weeks 1-6) and dactinomycin IV and doxorubicin hydrochloride IV over 15-120 minutes on days 1 and 22 (weeks 1 and 4). REVISED UH-1 REGIMEN (stage IV BWT with focal anaplasia; stage II-IV BWT with diffuse anaplasia; or stage I-IV malignant rhabdoid tumor of the kidney): Patients receive vincristine sulfate IV on days 1, 8, and 15 (weeks 1-3); doxorubicin hydrochloride IV over 15-120 minutes on day 1 (week 1); cyclophosphamide IV over 1 hour on day 1 and on days 22-25 (weeks 1 and 4); carboplatin IV over 1 hour on day 22 (week 4); and etoposide phosphate IV over 1 hour on days 22-25 (week 4). (*Note: This regimen has been closed based on toxicity from AREN0321.) EE-4A REGIMEN (high-risk, stage I-II unilateral WT with contralateral NR or predisposition syndrome or diffuse hyperplastic perilobar NRs [DHPLNR]): Patients receive vincristine sulfate IV over 1 minute on days 1, 8, 15, 22, 29, and 36 (weeks 1-6) and dactinomycin IV over 1-5 minutes on days 1 and 22 (weeks 1 and 4). Patients are evaluated at week 6. If partial nephrectomy is feasible, patients proceed to definitive surgery and lymph node sampling followed by postoperative therapy. If partial nephrectomy is not feasible, patients receive additional chemotherapy (as above with the same or a different set of regimen) followed by definitive surgery at week 12 and postoperative therapy OR patients proceed to a different chemotherapy regimen. POSTOPERATIVE THERAPY: Patients receive postoperative therapy according to histology after preoperative chemotherapy and according to the highest assigned risk for either kidney. EE-4A regimen (BWT with complete resection of all gross tumors at diagnosis with stage I-II favorable histology; BWT with complete response [CR] by imaging after 6 weeks of preoperative chemotherapy; completely necrotic stage I-II BWT; intermediate-risk stage I BWT; unilateral WT stage I-II with CR by imaging after 6-12 weeks of preoperative chemotherapy; completely necrotic stage I-II unilateral WT; or intermediate-risk stage I-II unilateral WT): Patients receive vincristine sulfate IV over 1 minute on days 43, 50, 57, 64, 85, 106, and 127 (weeks 7-10, 13, 16, and 19) and dactinomycin IV over 1-5 minutes on days 43, 64, 85, 106, and 127 (weeks 7, 10, 13, 16, and 19). DD-4A REGIMEN (intermediate-risk, stage II BWT; stage I BWT with blastemal predominance; or stage I unilateral WT with blastemal predominance): Patients receive vincristine sulfate IV over 1 minute on days 1, 8, 15, 22, 29, and 36 (weeks 1-6); dactinomycin IV over 1-5 minutes on day 1 (week 1); and doxorubicin hydrochloride IV over 15-120 minutes on day 22 (week 4). Patients then receive vincristine sulfate IV over 1 minute on days 43, 50, 57, 64, 85, 106, 127, 148, and 169 (weeks 7-10, 13, 16, 19, 22, and 25); dactinomycin IV over 1-5 minutes on days 43, 85, 127, and 169 (weeks 7, 13, 19, and 25); and doxorubicin hydrochloride over 15-120 minutes on days 63, 106, and 148 (weeks 10, 16, and 22). Some patients may also undergo radiotherapy. DD-4A REGIMEN AND RADIOTHERAPY (BWT with complete resection of all gross tumors at diagnosis with stage III-IV favorable histology, completely necrotic stage III-IV BWT; intermediate-risk, stage III-IV BWT; stage I BWT with diffuse anaplasia; stage I-III BWT with focal anaplasia; stage I unilateral WT with diffuse anaplasia; stage I unilateral WT with focal anaplasia; or intermediate-risk, stage III-IV unilateral WT): Patients receive DD-4A regimen as above. Patients also undergo concurrent radiotherapy. REGIMEN I (stage II BWT with blastemal predominance or stage II unilateral WT with blastemal predominance): Patients receive vincristine sulfate IV over 1 minute on days 43, 50, 57, 71, 78, 85, 92, 127, and 169 (weeks 7-9, 11-14, 19, and 25); doxorubicin hydrochloride IV over 15-120 minutes on days 43, 85, 127, and 169 (weeks 7, 13, 19, and 25); cyclophosphamide IV over 15-30 minutes on days 43, 64, 85, 106, 127, 148, and 169 (weeks 7, 10, 13, 16, 19, 22, and 25); and etoposide phosphate IV over 1 hour on days 64, 106, and 148 (weeks 10, 16, and 22). REGIMEN I AND RADIOTHERAPY (stage III-IV BWT with blastemal predominance or stage III-IV unilateral WT with blastemal predominance): Patients receive regimen I as above. Patients also undergo concurrent radiotherapy. REVISED UH-1 REGIMEN AND RADIOTHERAPY (stage IV BWT with focal anaplasia; stage II-IV BWT with diffuse anaplasia; stage IV unilateral WT with focal anaplasia; stage II-IV unilateral WT with diffuse anaplasia; and stage I-IV malignant rhabdoid tumor of the kidney; or DHPLNR with anaplasia): Patients receive vincristine sulfate IV over 1 minute on days 64, 71, 78, 85, 92, 99, 148, 155, 162, 190, 197, and 204 (weeks 10-15, 22-24, and 28-30); doxorubicin hydrochloride IV over 15-120 minutes on days 64, 85, 148, and 190 (weeks 10, 13, 22, and 28); cyclophosphamide IV over 15-30 minutes on days 43-46, 64, 85, 106-109, 127-130, 148, 169-172, and 190 (weeks 7, 10, 13, 16, 19, 22, 25, and 28); carboplatin IV over 1 hour on days 43, 106, 127, and 169 (weeks 7, 16, 19, and 25); and etoposide phosphate IV over 1 hour on days 43-46, 106-109, 127-130, and 169-172 (weeks 7, 16, 19, and 25). Patients also undergo radiotherapy. VAD REGIMEN (DHPLNR with favorable histology WT with viable elements): Patients receive vincristine sulfate IV over 1 minute on days 43, 50, 57, 64, 71, and 78 (weeks 7-12) and dactinomycin IV over 1-5 minutes and doxorubicin hydrochloride IV over 15-120 minutes on days 43 and 64 (weeks 7 and 10). After completion of study treatment, patients are followed up periodically for 10 years.

Who is eligible to participate?

Inclusion criteria: Patients must be < 30 years old at the time of initial 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: 1. Synchronous bilateral Wilms tumors*; or 2. 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 3. Multicentric Wilms tumor (any age) (to be eligible, these patients must not undergo any nephrectomy at diagnosis); or 4. Unilateral Wilms tumor 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 5. Diffuse hyperplastic perilobar nephroblastomatosis (unilateral or bilateral) defined by central radiological review; or 6. 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.

Last updated:

10/9/2014

NCT ID:

NCT00945009

IRB Number:

09-004942