NCT00379340

Combination Chemotherapy With or Without Radiation Therapy in Treating Young Patients With Newly Diagnosed Stage III or Stage IV Wilms' Tumor

Treatment of Newly Diagnosed Higher Risk Favorable Histology Wilms Tumors

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 395 (actual)
• Sponsor: Children's Oncology Group · Network
• Sex: All
• Age: 29 Years
• Healthy volunteers: Not accepted

Summary

This phase III trial is studying how well combination chemotherapy with or without radiation therapy works in treating young patients with newly diagnosed stage III or stage IV Wilms' tumor. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving more than one drug (combination chemotherapy) with or without radiation therapy may kill more tumor cells.

Detailed description

PRIMARY OBJECTIVES: I. To demonstrate that patients with Stage IV favorable histology (FH) Wilms tumor with pulmonary metastases only, who have complete resolution of the pulmonary lesions after 6 weeks of DD-4A chemotherapy (vincristine, dactinomycin, and doxorubicin), called Rapid Complete Responders (RCR), will have at least an 85% 4 year event-free survival (EFS) after therapy with additional DD-4A and without whole lung irradiation. II. To demonstrate that Stage IV FH patients who do not have resolution of pulmonary metastases by Week 6, called Slow Incomplete Responders (SIR), will have a 4 year EFS of 85% with the addition of cyclophosphamide and etoposide to a modified Regimen DD-4A (Regimen M). III. To improve the 4 year EFS to 75% for patients with Stage III or IV FH Wilms tumor with loss of heterozygosity (LOH) for chromosomes 1p and 16q. SECONDARY OBJECTIVE: I. To determine the relationship between the burden of pulmonary metastatic disease and outcome in Stage IV FH patients. OUTLINE: This is a multicenter study. REGIMEN DD4A (weeks 1-6): Patients receive dactinomycin IV over 1-5 minutes once in week 1; vincristine IV once in weeks 1-6; and doxorubicin hydrochloride IV over 15 minutes once in week 4 in the absence of disease progression or unacceptable toxicity. Patients with pulmonary and extra-pulmonary metastases at diagnosis undergo radiotherapy once daily beginning in week 1 and continuing for 5-14 days. After completion of DD4A chemotherapy (week 6), patients undergo evaluation. Patients with stage IV disease and pulmonary metastases only with no loss of heterozygosity (LOH) who are rapid complete responders (RCR) (i.e., pulmonary metastases disappear) proceed to regimen DD4A (weeks 7-25). All other patients (i.e., patients with stage III or IV disease and LOH of both 1p and 16q; stage IV disease with pulmonary metastases only who are slow incomplete responders \[SIR\] \[i.e., pulmonary metastases do not disappear\]; or stage IV disease with nonpulmonary metastases or with nonpulmonary metastases in combination with pulmonary metastases) proceed to regimen M (weeks 7-31). Patients with initially unresectable or incompletely resected tumors are reevaluated at week 6, and if resectable, undergo surgery and then proceed to either regimen DD4A or regimen M as described above. REGIMEN DD4A (weeks 7-25): Patients receive dactinomycin IV over 1-5 minutes once in weeks 7, 13, 19, and 25; vincristine IV once in weeks 7-10, 13, 16, 19, 22, and 25; and doxorubicin hydrochloride IV over 15 minutes once in weeks 10, 16, and 22 in the absence of disease progression or unacceptable toxicity. REGIMEN M (weeks 7-31): Patients receive cyclophosphamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 in weeks 7, 10, 19, and 25; vincristine IV once in weeks 8, 9, 11, 12, 13, 16, 22, 28, and 31; and dactinomycin IV and doxorubicin hydrochloride IV over 15 minutes once in weeks 13, 16, 22, 28, and 31 in the absence of disease progression or unacceptable toxicity. Patients with pulmonary metastases only who are SIR also undergo whole lung radiotherapy once daily beginning in week 7 and continuing for 5-14 days. NOTE: Patients who begin study treatment after undergoing resection of pulmonary metastases are treated according to regimen DD4A (weeks 1-25) and undergo whole lung radiotherapy for 5-14 days beginning in week 1. After completion of study treatment, patients are followed periodically for 10 years.

Conditions

• Stage III Kidney Wilms Tumor
• Stage IV Kidney Wilms Tumor

Interventions

Type	Name	Description
RADIATION	3-Dimensional Conformal Radiation Therapy
PROCEDURE	Conventional Surgery
DRUG	Cyclophosphamide	Given IV
BIOLOGICAL	Dactinomycin	Given IV
DRUG	Doxorubicin Hydrochloride	Given IV
DRUG	Etoposide	Given IV
DRUG	Vincristine Sulfate Liposome	Given IV

Timeline

• Start date: 2007-04-30
• Primary completion: 2016-06-30
• Completion: 2026-11-18
• First posted: 2006-09-21
• Last updated: 2026-03-17
• Results posted: 2017-06-14

Locations

227 sites across 7 countries: United States, Australia, Canada, Israel, New Zealand, Puerto Rico, Switzerland