Trial Information

NATIONAL WILMS TUMOR STUDY-5 -- TREATMENT OF RELAPSED PATIENTS

OBJECTIVES:

- Determine the 2-year second-event-free survival after vincristine (VCR) and
dactinomycin (DACT) with or without doxorubicin (DOX), depending on the site of relapse
and presence of microscopic residual disease, in children with relapsed Wilm's tumor
previously treated with nephrectomy alone as initial therapy.

- Determine whether the 2-year second-event-free survival after intensive doxorubicin,
etoposide (VP-16), cyclophosphamide (CTX), and carboplatin (CBDCA) plus radiotherapy to
residual disease is at least 40% higher in patients with relapsed Wilm's tumor
previously treated with Regimen EE-4A as initial therapy and without loss of
heterozygosity for chromosomes 16q and 1p and increased DNA content in tumor cells than
for similarly treated patients with loss of heterozygosity for chromosome 16q or 1p or
increased DNA content in tumor cells.

- Determine whether the 4-year post-relapse survival after intensive VP-16, CTX, and
CBDCA is at least 40% higher in patients with relapsed Wilm's tumor previously treated
with Regimen DD-4A as initial therapy and without loss of heterozygosity for
chromosomes 16q and 1p and increased DNA content in tumor cells than for similarly
treated patients with loss of heterozygosity for chromosome 16q or 1p or increased DNA
content in tumor cells.

- Determine whether the rates of complete and partial response exceed 20% in patients
with relapsed clear cell sarcoma of the kidney or diffuse anaplastic Wilms' tumor
treated with CBDCA combined with VP-16.

OUTLINE: This is a multicenter study.

Patients are assigned to a treatment group based on initial therapy and histology. Patients
under age 2 at diagnosis who were previously treated with nephrectomy as initial therapy for
stage I favorable histology Wilms' tumor weighing less than 550 grams are assigned to group
A. Patients who received Regimen EE-4A as initial therapy for Wilms' tumor are assigned to
group B. Patients who received Regimen DD-4A as initial therapy for Wilms' tumor are
assigned to group C. Patients with clear cell sarcoma of the kidney or diffuse anaplastic
Wilms' tumor are assigned to group D.

Group A

- Treatment is determined by site of relapse and the presence of microscopic or gross
residual disease after attempted resection of relapsed disease. Children with suspected
intra-abdominal recurrence undergo exploratory surgery to determine the site of
recurrence and to obtain tissue for microscopic examination. Patients with stage I
disease after recurrence are treated with regimen EE-4A. Patients with stage II or III
disease are treated with regimen DD-4A.

- Regimen EE-4A: Patients receive dactinomycin (DACT) IV on weeks 0, 3, 6, 9, 12,
15, and 18 and vincristine (VCR) IV on weeks 1-10, 12, 15, and 18 in the absence
of disease progression.

- Regimen DD-4A: Patients receive DACT IV on weeks 0, 6, 12, 18, and 24; VCR IV
weekly on weeks 1-10, 12, 15, 18, 21, and 24; doxorubicin (DOX) IV on weeks 3, 9,
15, and 21; and abdominal radiotherapy in the absence of disease progression.

Group B

- Patients undergo resection. After resection, patients receive regimen I comprising DOX
IV on weeks 0, 6, 12, 18, and 24; VCR IV on weeks 1, 2, 4, 5-8, 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; and etoposide (VP-16) IV over 1 hour (after CTX
infusion) on days 1-5 of weeks 3, 9, 15, and 21 in the absence of disease progression.
Filgrastim (G-CSF) is administered subcutaneously (SC) beginning 24 hours after
completion of chemotherapy and continuing until blood counts recover. Patients undergo
radiotherapy to site of recurrence beginning within 1 week after initiation of
chemotherapy.

Group C

- Induction: Patients receive CTX IV over 1 hour on days 1-5 of weeks 0 and 3; VP-16 IV
over 1 hour (after CTX infusion) on days 1-5 of weeks of 0 and 3 and on days 1-3 of
weeks 6 and 9; and carboplatin (CBDCA) IV over 6 hours on days 1 and 2 of weeks 6 and 9
in the absence of disease progression. G-CSF is administered SC beginning 24 hours
after completion of CTX/VP-16 or CBDCA/VP-16 and continuing until blood counts recover.

- Surgery: Patients with detectable disease undergo resection on week 13. If complete
resection is not achieved or if it is deemed impossible, resection must be attempted no
later than 3 weeks after consolidation radiotherapy.

- Consolidation: Beginning within 9 days of surgery, patients receive CTX IV over 1 hour
on days 1-5 of week 1; VP-16 IV over 1 hour (after CTX infusion) on days 1-5 of week 1
and on days 1-3 of week 4; CBDCA IV over 6 hours on days 1 and 2 of week 4; G-CSF as in
induction; and radiotherapy in the absence of disease progression. Patients with
complete or partial response after resection and/or radiotherapy proceed to maintenance
therapy.

- Maintenance: Patients receive CTX IV over 1 hour on days 1-5 of weeks 0 and 3; VP-16 IV
over 1 hour on days 1-5 of weeks 0 and 3 and on days 1-3 of weeks 6 and 9; CBDCA IV
over 6 hours on days 1 and 2 of weeks 6 and 9; and G-CSF as in induction. Treatment
continues every 12 weeks for 6 courses in the absence of disease progression.

Group D

- Patients receive CBDCA IV over 6 hours on days 1 and 2 and VP-16 IV over 1 hour (after
CBDCA infusion) on days 1-3 of weeks 0 and 3. Treatment continues weekly for 6 courses
in the absence of disease progression.

Patients are followed every 3 months for 15 months, every 6 months for 1 year, and then
annually for 3 years.

PROJECTED ACCRUAL: Not specified