Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

RATIONALE: 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.

PURPOSE: 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.

Further Study Information

OBJECTIVES:

Primary

• 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.

• 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).

• 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

• 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., 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.

PROJECTED ACCRUAL: A total of 400 patients will be accrued for this study.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Newly diagnosed Wilms tumor meeting 1 of the following criteria:

• Stage IV disease with favorable histology with or without loss of heterozygosity (LOH) for 1p and 16q

• Stage III disease with favorable histology with LOH for 1p and 16q transferring from clinical trial COG-AREN0532

• Patients must begin therapy within 14 days after surgery or biopsy (day 0), unless medically contraindicated

• Extra-pulmonary metastases include lymph node involvement in the hilum and/or mediastinum deemed by the treating institution to represent malignant disease, or positive cytology-proven pleural effusions

• No bilateral Wilms tumors (stage IV)

• Patients should be referred to COG-AREN0534

• Previously enrolled in clinical trial COG-AREN03B2

PATIENT CHARACTERISTICS:

• Karnofsky performance status (PS) 50-100% (for patients > 16 years of age) OR Lansky PS 50-100% (for patients ≤ 16 years of age)

• Bilirubin ≤ 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

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior tumor-directed chemotherapy or radiotherapy unless transferring from clinical trial COG-AREN0532 OR treatment for emergent issues, as medically indicated

• No concurrent aprepitant

Trial Contact Information

Trial Lead Organizations/Sponsors

Children's Oncology Group

David Bryan Dix

Study Chair

U.S.A.
Alabama
	Birmingham
	UAB Comprehensive Cancer Center
		Alyssa T Reddy	Ph: 205-934-0309
California
	Arcadia
	Children's Oncology Group
		David B Dix	Ph: 604-875-2316
			Email: ddix@cw.bc.ca
	Sacramento
	University of California Davis Cancer Center
		Jay Michael S Balagtas	Ph: 916-734-3089
Idaho
	Boise
	Mountain States Tumor Institute at St. Luke's Regional Medical Center
		Eugenia Chang	Ph: 800-845-4624
Michigan
	Kalamazoo
	Western Michigan University School of Medicine Clinics
		Jeffrey S Lobel	Ph: 800-227-2345
New Jersey
	Summit
	Overlook Hospital
		Steven L Halpern	Ph: 973-971-5900
Oregon
	Portland
	Legacy Emanuel Hospital and Health Center and Children's Hospital
		Janice F Olson	Ph: 503-413-2560
South Carolina
	Greenville
	Cancer Centers of the Carolinas - Faris Road
		Cary E Stroud	Ph: 864-241-6251
Australia
Queensland
	Herston
	Royal Brisbane and Women's Hospital
		Helen Irving	Ph: 888-823-5923
			Email: ctsucontact@westat.com
Canada
Ontario
	Hamilton
	McMaster Children's Hospital at Hamilton Health Sciences
		Carol Portwine	Ph: 905-521-2100ext74595

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00379340
Information obtained from ClinicalTrials.gov on April 04, 2013

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