Vincristine, Dactinomycin, and Doxorubicin With or Without Radiation Therapy or Observation Only in Treating Younger Patients Who Are Undergoing Surgery for Newly Diagnosed Stage I, Stage II, or Stage III Wilms' Tumor

PRIMARY OBJECTIVES:

I. Evaluate the overall and event-free survival of younger patients with newly diagnosed
stage I favorable histology Wilms' tumor (< 2 years of age and < 550gms) treated with
nephrectomy only (very low risk), or with newly diagnosed stage III favorable histology
Wilms tumor with possible nephrectomy followed by vincristine, dactinomycin, doxorubicin
hydrochloride, and radiotherapy (standard risk).

SECONDARY OBJECTIVES:

I. Determine the effects of adding doxorubicin hydrochloride to the regimen for patients
with stage I or II favorable histology found to have a high-risk biological marker.

II. Determine whether the omission of adjuvant therapy increases the incidence of
contralateral kidney lesions in patients with very low-risk disease treated by nephrectomy
and observation only.

III. Determine whether the omission of adjuvant therapy increases the incidence of renal
failure in patients with very low-risk disease who have metachronous relapse.

IV. Correlate study outcomes in patients with standard-risk disease with biological data
from tissue collections on protocol study COG-AREN03B2.

OUTLINE: This is a multicenter study. Patients are stratified according to clinical and
biological risk factors (very low risk vs standard risk).

STRATUM I: (very low-risk disease) Patients undergo nephrectomy only. If they meet criteria,
they are then observed periodically for 5 years. Patients with recurrent disease undergo
surgery (immediate or delayed) and receive chemotherapy as in stratum III. Patients with no
metachronous renal disease receive radiotherapy. Patients with metachronous disease undergo
renal-sparing surgery and chemotherapy as in stratum III, but no radiotherapy. Treatment
continues for up to 25 weeks.

STRATUM II: (standard-risk, stage I or II disease with adverse biological marker) Patients
undergo nephrectomy. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV
beginning on day 1, every week for 10 weeks then every 3 weeks for a total of 15 doses.
Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin
hydrochloride IV for a total of 5 doses of dactinomycin and 4 doses of doxorubicin.
Treatment continues for up to 25 weeks.

STRATUM III: (standard-risk, stage III disease) Patients undergo nephrectomy, if feasible,
or biopsy. For patients who undergo biopsy only, definitive surgery is undertaken at week 7
or 13. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on
day 1 every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive
dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV
for a total of 5 doses of dactinomycin and 4 dose of doxorubicin hydrochloride. Patients
undergo radiotherapy over 5-7 days after nephrectomy. Treatment continues for up to 25
weeks.

After completion of study treatment, patients are followed periodically for up to 8 years.

Inclusion Criteria:

- Histologically confirmed Wilms' tumor

- Newly diagnosed stage I-III disease

- Favorable histology

- No moderate- or high-risk Wilms' predisposition syndromes

- Must meet 1 of the following disease stratification categories:

- Very low-risk disease

- Stage I disease

- Age < 2 years

- Tumor weight < 550 g

- Regional lymph nodes histologically negative (must have been sampled)

- No pulmonary metastases on CT scan of chest

- No synchronous bilateral Wilms tumors (Stage V)

- Not predisposed to develop bilateral Wilms tumors, defined as unilateral
Wilms tumor and any of the following:

- Aniridia

- Beckwith-Wiedemann syndrome

- Simpson-Golabi-Behmel syndrome

- Denys-Drash syndrome or other associated genito-urinary anomalies

- Multicentric WT or unilateral WT with contralateral nephrogenic
rest(s) in a child < 1 year of age

- Diffuse hyperplastic perilobar nephroblastomatosis

- Standard-risk disease meeting 1 of the following criteria:

- Disease does not require radiotherapy

- LOH at chromosomes 1p and 16q for stage I or II

- Stage I disease meeting 1 of the following criteria:

- Age ≥ 2 years to age < 30 years

- Tumor weight ≥ 500 g

- Stage II disease

- Age < 30 years

- Any tumor weight

- Disease requires radiotherapy

- No LOH at chromosomes 1p and 16q*

- Stage III disease

- Must be enrolled on protocol COG-AREN03B2

- Karnofsky performance status (PS) 50-100% for patients > 16 years old

- Lansky PS 50-100% for patients ≤ 16 years old

- Bilirubin (direct) ≤ 1.5 times upper limit of normal (ULN)

- AST or ALT < 2.5 times ULN

- Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by
radionuclide angiogram (standard-risk disease)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patient must use effective contraception

- No prior tumor-directed chemotherapy or radiotherapy

- Patients transferring from AREN03B2 with LOH 1p and 16q allowed