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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Treatment of Newly Diagnosed Higher Risk Favorable Histology Wilms Tumors

Brief 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' 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 Summary:

PRIMARY OBJECTIVES:

I. Determine the 4-year event-free survival (EFS) of patients with stage IV favorable histology (FH) Wilms' tumor 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' tumor 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' tumor.

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 both 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., all pulmonary metastases disappear) proceed to regimen DD4A (weeks 7-25).

  • EFS of patients with stage IV and rapid complete response (RCR) of lung metastases [ Time Frame: At 4 years ]
    The methods of Woolson to compare the results to the fixed null outcomes as defined above and using an O'Brien-Fleming boundary (truncated at 3 standard deviations) will be used.
  • EFS of patients with stage IV and slow incomplete response (SIR) of lung metastases [ Time Frame: At 4 years ]
    The methods of Woolson to compare the results to the fixed null outcomes as defined above and using an O'Brien-Fleming boundary (truncated at 3 standard deviations) will be used.
  • EFS of patients with stage IV, non lung disease only, and stage III with LOH 1p and 16q [ Time Frame: At 4 years ]


    • Original Primary Outcome:

    Current Secondary Outcome: Correlate between the burden of pulmonary metastatic disease with outcome in patients with stage IV FH Wilms' tumor [ Time Frame: At 4 years ]

    CT scans of the abdomen and of the chest will be submitted in digital format through QARC (chest X-rays will not be requested) and reviewed and classified prospectively. Tumor burden will be compared with relapse-free survival to determine whether pulmonary tumor burden is a prognostic factor


    Original Secondary Outcome:

    Information By: Children's Oncology Group

    Dates:
    Date Received: September 19, 2006
    Date Started: February 2007
    Date Completion:
    Last Updated: October 31, 2016
    Last Verified: October 2016