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

Official Title

Treatment of Newly Diagnosed Higher Risk Favorable Histology Wilms Tumours

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 Favorable Histology Wilms' tumour. Drugs used in chemotherapy work in different ways to stop the growth of tumour cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumour cells. Giving more than one drug (combination chemotherapy) with or without radiation therapy may kill more tumour cells.

Trial Description

Primary Outcome:

  • EFS of patients with stage IV and rapid complete response (RCR) of lung metastases
  • EFS of patients with stage IV and slow incomplete response (SIR) of lung metastases
  • EFS of patients with stage IV, non lung disease only, and stage III with LOH 1p and 16q
Secondary Outcome:
  • Correlate between the burden of pulmonary metastatic disease with outcome in patients with stage IV FH Wilms' tumour
PRIMARY OBJECTIVES:
I. Determine the 4-year event-free survival (EFS) of patients with stage IV favourable histology (FH) Wilms' tumour with pulmonary metastases only who have complete resolution of pulmonary lesions without whole lung irradiation treated with DD4A chemotherapy comprising vincristine, dactinomycin, and doxorubicin hydrochloride. II. Determine the 4-year EFS of these patients who do not have resolution of pulmonary metastases by week 6 treated with the addition of cyclophosphamide and etoposide to a modified-regimen DD4A (regimen M). III. Determine the 4-year EFS of patients with stage III or IV FH Wilms' tumour with loss of heterozygosity for chromosomes 1p and 16q treated with regimen M. SECONDARY OBJECTIVES:
I. Correlate the burden of pulmonary metastatic disease with outcome in patients with stage IV FH Wilms' tumour. OUTLINE:

This is a multicentre 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 both pulmonary and extra-pulmonary metastases at diagnosis undergo radiation therapy 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., all 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 tumours 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 or 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 radiation therapy once daily beginning in week 7 and continuing for 5-14 days. NOTE: Patients who begin study treatment after undergoing resection of all pulmonary metastases are not eligible for this study. It is recommended that these patients be treated as per the current gold standard of therapy which is chemotherapy according to regimen DD4A (weeks 1-25) and whole lung radiation therapy for 5-14 days beginning in week 1. After completion of study treatment, patients are followed periodically for 10 years.

View this trial on ClinicalTrials.gov

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Resources

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