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About
This phase III trial is studying vincristine, dactinomycin, and doxorubicin with or without radiation therapy or observation only to see how well they work in treating patients undergoing surgery for newly diagnosed stage I, stage II, or stage III Wilms' tumor. Drugs used in chemotherapy, such as vincristine, dactinomycin, and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors.Giving these treatments after surgery may kill any tumor cells that remain after surgery. Sometimes, after surgery, the tumor may not need additional treatment until it progresses. In this case, observation may be sufficient.
Full description
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.
Additionally, patients undergo chest X-ray, computed tomography (CT) or magnetic resonance imaging (MRI), ultrasound, echocardiography, and blood sample collection throughout the study.
After completion of study treatment, patients are followed periodically for up to 8 years.
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Inclusion and exclusion criteria
Inclusion Criteria:
Histologically confirmed Wilms' tumor
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:
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:
Stage II disease
Disease requires radiotherapy
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
Primary purpose
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808 participants in 3 patient groups
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Data sourced from clinicaltrials.gov
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