Trial Information

NATIONAL WILMS TUMOR STUDY-5 -- THERAPEUTIC TRIAL AND BIOLOGY STUDY

OBJECTIVES:

- Increase survival rate of children with favorable histology (FH) Wilms' tumor and other
childhood renal tumors.

- Determine whether loss of heterozygosity for chromosome 16q or 1p in tumor tissue is
associated with a poorer prognosis in children with FH Wilms' tumor.

- Determine whether increased DNA content in tumor cells is associated with a poorer
prognosis in children with FH Wilms' tumor.

- Decrease the acute and long-term morbidity in children with Wilms' tumor by limiting
initial therapy and consistently using the same regimen (protocol NWTS-5/R) for
patients who relapse following initial treatment.

- Improve overall and disease-free survival of patients with renal tumors of unfavorable
histology, including Wilms' tumor with diffuse anaplasia and clear cell sarcoma of the
kidney, using a new treatment regimen that includes etoposide (VP-16) and
cyclophosphamide (CTX).

- Improve overall and disease-free survival in patients with malignant rhabdoid tumor of
the kidney using a new treatment regimen that includes carboplatin, VP-16, and CTX.
(The rhabdoid tumor stratum closed to accrual effective 07/13/2001)

- Provide data regarding loss of heterozygosity for chromosomes 11p15, 16q, and 1p, age
at diagnosis, precursor lesions (perilobar, intralobar, nephroblastomatosis),
bilaterality, and presence of congenital anomalies required for the completion of
protocol A0026 (a case-control study of risk factors for Wilms' tumor).

OUTLINE: This is a multicenter study. Patients are assigned to one of nine strata based on
tumor histology, stage, tumor weight, and age.

- Stratum 1 (stage I favorable histology (FH) Wilms' tumor, under 24 months of age, and
tumor weight less than 550 g): After nephrectomy, patients receive regimen EE-4A
comprising dactinomycin (DACT) IV weekly on weeks 0, 3, 6, 9, 12, 15, and 18 and
vincristine (VCR) IV weekly on weeks 1-10, 12, 15, and 18.

- Stratum 2 (stage I FH Wilms' tumor and age 24 months and over or tumor weight at least
550 g; stage I focal anaplastic (FA) or diffuse anaplastic (DA) Wilms' tumor): Patients
receive therapy as in stratum 1.

- Stratum 3 (stage II FH Wilms' tumor): Patients receive therapy as in stratum 1.

- Stratum 4 (stage III FH Wilms' tumor; stage II or III FA Wilms' tumor): After
nephrectomy, patients receive regimen DD-4A comprising DACT IV weekly on weeks 0, 6,
12, 18, and 24; doxorubicin IV weekly on weeks 3, 9, 15, and 21; and VCR IV weekly on
weeks 1-10, 12, 15, 18, 21, and 24. Patients also undergo abdominal radiotherapy.

- Stratum 5 (stage IV FH or FA Wilms' tumor): Patients receive chemotherapy as in stratum
4, abdominal radiotherapy, and whole lung radiotherapy (at the discretion of the
investigator).

- Stratum 6 (stage V FH, FA, or DA Wilms' tumor ): After bilateral biopsy, patients with
FH receive chemotherapy as in stratum 1 or 4. Patients with FA or DA receive
chemotherapy as in stratum 7.

- Stratum 7 (stages I-IV clear cell sarcoma): After nephrectomy, patients receive VCR IV
weekly on weeks 1, 2, 4-8, 10-13, 18, and 24; cyclophosphamide (CTX) IV over 1 hour on
days 1-3 of weeks 6, 12, 18, and 24 and on days 1-5 of weeks 3, 9, 15, and 21;
doxorubicin IV (beginning after CTX infusion) weekly on weeks 0, 6, 12, 18, and 24; and
etoposide (VP-16) IV over 1 hour (beginning after CTX infusion) on days 1-5 of weeks 3,
9, 15, and 21. Filgrastim (G-CSF) is administered subcutaneously (SC) beginning 24
hours after completion of chemotherapy and continuing until blood counts recover.
Patients also undergo abdominal radiotherapy and whole lung radiotherapy (if pulmonary
metastases are present).

- Stratum 8 (stages II-IV DA Wilms' tumor): Patients receive treatment as in stratum 7.

- Stratum 9 (stages I-IV rhabdoid tumor): After nephrectomy, patients receive carboplatin
IV on days 1-2 and VP-16 IV over 1 hour (beginning after carboplatin infusion) on days
1-3 of weeks 0, 3, 9, 12, 18, and 21 and CTX IV over 1 hour on days 1-5 of weeks 6, 15,
and 24. G-CSF is administered as in stratum 7. Patients also undergo radiotherapy. (The
rhabdoid tumor stratum closed to accrual effective 07/13/2001.) After completion of
chemotherapy, patients undergo second-look laparotomy and partial nephrectomy or wedge
excision (if feasible). After second-look surgery, patients without persistent or
residual disease resume chemotherapy.

Patients are followed every 3 months for 5 years, every 6 months for 2 years, and then
annually for 3 years.

PROJECTED ACCRUAL: A total of 207 patients will be accrued for the treatment portion of this
study. (The rhabdoid tumor stratum closed to accrual effective 07/13/2001.)