Overview

This trial is active, not recruiting.

Conditions stage iii wilms tumor with loss of heterozygosity (loh) for 1p and 16q, stage iv wilms tumor
Treatments doxorubicin hydrochloride, liposomal vincristine sulfate, conventional surgery, 3-dimensional conformal radiation therapy, dactinomycin, cyclophosphamide, etoposide
Phase phase 3
Sponsor Children's Oncology Group
Collaborator National Cancer Institute (NCI)
Start date February 2007
End date October 2015
Trial size 395 participants
Trial identifier NCT00379340, AREN0533, CDR0000496508, COG-AREN0533, NCI-2009-00419, U10CA098543

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
REGIMEN DD4A (weeks 1-6): Patients receive dactinomycin IV; liposomal vincristine sulfate IV; and doxorubicin hydrochloride IV. Patients with pulmonary and extra-pulmonary metastases at diagnosis undergo 3-dimensional conformal radiation therapy to all sites of metastatic disease. Patients with initially unresectable tumors at diagnosis are reevaluated at week 6, and if resectable, undergo conventional surgery and then proceed to either regimen DD4A or regimen M based on their pulmonary response at week 6. REGIMEN DD4A (weeks 7-25): Patients receive dactinomycin IV; liposomal vincristine sulfate IV; doxorubicin hydrochloride IV. REGIMEN M (weeks 7-31): Patients receive cyclophosphamide IV; liposomal vincristine sulfate IV; dactinomycin IV; doxorubicin hydrochloride IV and etoposide IV. Patients with pulmonary metastases only who are slow incomplete responders (SIR) also undergo whole lung 3-dimensional conformal radiation therapy.
doxorubicin hydrochloride ADM
Given IV
liposomal vincristine sulfate liposomal vincristine
Given IV
conventional surgery surgery, conventional
3-dimensional conformal radiation therapy 3D conformal radiation therapy
dactinomycin ACT-D
Given IV
cyclophosphamide CPM
Given IV
etoposide EPEG
Given IV

Primary Outcomes

Measure
EFS of patients with stage IV and rapid complete response (RCR) of lung metastases
time frame: At 4 years
EFS of patients with stage IV and slow incomplete response (SIR) of lung metastases
time frame: At 4 years
EFS of patients with stage IV, non lung disease only, and stage III with LOH 1p and 16q
time frame: At 4 years

Secondary Outcomes

Measure
Correlate between the burden of pulmonary metastatic disease with outcome in patients with stage IV FH Wilms' tumor
time frame: At 4 years

Eligibility Criteria

Male or female participants up to 29 years old.

Inclusion Criteria: - 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, unless medically contraindicated - No bilateral Wilms' tumors (stage IV) - Patients should be referred to COG-AREN0534 - Previously enrolled in clinical trial COG-AREN03B2 - 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 - 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

Additional Information

Official title Treatment of Newly Diagnosed Higher Risk Favorable Histology Wilms Tumors
Principal investigator David Dix, MD
Description 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). 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 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 radiotherapy 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 radiotherapy for 5-14 days beginning in week 1. After completion of study treatment, patients are followed periodically for 10 years.
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by Children's Oncology Group.