NCT00379340 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2026-07-24

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

Event Free Survival Probability

→

outcome · POSTED

Event Free Survival (EFS) Probability

→

outcome · POSTED

Event Free Survival Probability

→

outcome · POSTED

Event Free Survival Associated With the Burden of Pulmonary Metastatic Disease

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

eligibility Criteria: Inclusion Criteria: * Patients must be less than 30 years of age at the time of diagnosis * Prior to enrollment on AREN0533, all patients must have been enrolled on AREN03B2 for central pathology review. Stage III patients with LOH transferring from AREN0532 may be enrolled on this study. Eligible patients for AREN0533 must be: * Newly diagnosed Stage IV favorable histology Wilms tumor with or without LOH 1p and 16q or * Newly diagnosed Stage III favorable histology Wilms tumor with LOH for 1p and 16q transferring from AREN0532 * Patients with bilateral Wilms tumors (Stage V) are not eligible for AREN0533 and should be directed to AREN0534 * Patients must begin protocol therapy on AREN0533 by Day 14 after surgery or biopsy, unless medically contraindicated * The Karnofsky performance status must be \>= 50 for patients \> 16 years of age and the Lansky performance status must be \>= 50 for patients =\< 16 years of age * Patients cannot have had prior tumor-directed chemotherapy or radiotherapy except for patients transferring from AREN0532 or those treated for emergent issues, as medically indicated * Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age (must be submitted for central review by Day 7) * Serum glutamic oxaloacetic transaminase (SGOT) aspartate aminotransferase (AST) or serum glutamic pyruvic transaminase (SGPT) alanine aminotransferase (ALT) \< 2.5 x ULN for age (must be submitted for central review by Day 7) * Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by radionuclide angiogram * Female patients of childbearing age must have a negative pregnancy test * Female patients who are lactating must agree to stop breast-feeding * Sexually active patients of childbearing potential must agree to use effective contraception
healthy Volunteers: false
maximum Age: 29 Years
sex: ALL
std Ages: CHILD
ADULT

Treatment arms and interventions

arm Groups

description
REGIMEN DD4A (weeks 1-6): Patients receive dactinomycin IV; vincristine IV; and doxorubicin hydrochloride IV. Patients with pulmonary and extra-pulmonary metastases at diagnosis undergo radiotherapy. 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. REGIMEN DD4A (weeks 7-25): Patients receive dactinomycin IV; vincristine IV; and doxorubicin hydrochloride IV. REGIMEN M (weeks 7-31): Patients receive cyclophosphamide IV; vincristine IV; and dactinomycin IV and doxorubicin hydrochloride IV. Patients with pulmonary metastases only who are SIR also undergo whole lung radiotherapy.
intervention Names
Radiation: 3-Dimensional Conformal Radiation Therapy
Procedure: Conventional Surgery
Drug: Cyclophosphamide
Biological: Dactinomycin
Drug: Doxorubicin Hydrochloride
Drug: Etoposide
Drug: Vincristine Sulfate Liposome
label
Treatment (chemotherapy, surgery, radiotherapy)
type
EXPERIMENTAL

interventions

arm Group Labels
Treatment (chemotherapy, surgery, radiotherapy)
name
3-Dimensional Conformal Radiation Therapy
other Names
3-dimensional radiation therapy
3D Conformal
3D CONFORMAL RADIATION THERAPY
3D CRT
3D radiotherapy
3D-CRT
Conformal Therapy
Radiation Conformal Therapy
Radiation, 3D Conformal
Three dimensional external beam radiation therapy (procedure)
type
RADIATION
arm Group Labels
Treatment (chemotherapy, surgery, radiotherapy)
name
Conventional Surgery
type
PROCEDURE
arm Group Labels
Treatment (chemotherapy, surgery, radiotherapy)
description
Given IV
name
Cyclophosphamide
other Names
(-)-Cyclophosphamide
2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
Asta B 518
B 518
B-518
B518
Carloxan
Ciclofosfamida
Ciclofosfamide
Cicloxal
Clafen
Claphene
type
DRUG
arm Group Labels
Treatment (chemotherapy, surgery, radiotherapy)
description
Given IV
name
Dactinomycin
other Names
Actinomycin A IV
Actinomycin C1
Actinomycin D
Actinomycin I1
Actinomycin IV
Actinomycin X 1
Actinomycin-[thr-val-pro-sar-meval]
Cosmegen
DACT
Dactinomycine
Lyovac Cosmegen
Meractinomycin
type
BIOLOGICAL
arm Group Labels
Treatment (chemotherapy, surgery, radiotherapy)
description
Given IV
name
Doxorubicin Hydrochloride
other Names
5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)
ADM
Adriacin
Adriamycin
Adriamycin Hydrochloride
Adriamycin PFS
Adriamycin RDF
ADRIAMYCIN, HYDROCHLORIDE
Adriamycine
Adriblastina
Adriblastine
Adrimedac
type
DRUG
arm Group Labels
Treatment (chemotherapy, surgery, radiotherapy)
description
Given IV
name
Etoposide
other Names
Demethyl Epipodophyllotoxin Ethylidine Glucoside
EPEG
Lastet
Toposar
Vepesid
VP 16
VP 16-213
VP 16213
VP-16
VP-16-213
VP-16213
VP16
type
DRUG
arm Group Labels
Treatment (chemotherapy, surgery, radiotherapy)
description
Given IV
name
Vincristine Sulfate Liposome
other Names
Marqibo
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 395
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Probability of no relapse, secondary malignancy, or death after 4 year in the study.
measure
Event Free Survival Probability
time Frame
4 years
description
Probability of no relapse, secondary malignancy, or death after 4 year in the study.
measure
Event Free Survival (EFS) Probability
time Frame
At 4 years
description
Probability of no relapse, secondary malignancy, or death after 4 year in the study
measure
Event Free Survival Probability
time Frame
At 4 years

secondary Outcomes

description
Probability of no relapse, secondary malignancy, or death after 4 year in the study.
measure
Event Free Survival Associated With the Burden of Pulmonary Metastatic Disease
time Frame
At 4 years

Full study description

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 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.

Source references

references

citation
Benedetti DJ, Varela CR, Renfro LA, Tornwall B, Dix DB, Ehrlich PF, Glick RD, Kalapurakal J, Perlman E, Gratias E, Seibel NL, Geller JI, Khanna G, Malogolowkin M, Grundy P, Fernandez CV, Dome JS, Mullen EA. Treatment of children with favorable histology Wilms tumor with extrapulmonary metastases: A report from the COG studies AREN0533 and AREN03B2 and NWTSG study NWTS-5. Cancer. 2024 Mar 15;130(6):947-961. doi: 10.1002/cncr.35099. Epub 2023 Nov 7.
pmid
37933882
type
DERIVED
citation
Madanat-Harjuoja LM, Renfro LA, Klega K, Tornwall B, Thorner AR, Nag A, Dix D, Dome JS, Diller LR, Fernandez CV, Mullen EA, Crompton BD. Circulating Tumor DNA as a Biomarker in Patients With Stage III and IV Wilms Tumor: Analysis From a Children's Oncology Group Trial, AREN0533. J Clin Oncol. 2022 Sep 10;40(26):3047-3056. doi: 10.1200/JCO.22.00098. Epub 2022 May 17.
pmid
35580298
type
DERIVED
citation
Dix DB, Fernandez CV, Chi YY, Mullen EA, Geller JI, Gratias EJ, Khanna G, Kalapurakal JA, Perlman EJ, Seibel NL, Ehrlich PF, Malogolowkin M, Anderson J, Gastier-Foster J, Shamberger RC, Kim Y, Grundy PE, Dome JS; AREN0532 and AREN0533 study committees. Augmentation of Therapy for Combined Loss of Heterozygosity 1p and 16q in Favorable Histology Wilms Tumor: A Children's Oncology Group AREN0532 and AREN0533 Study Report. J Clin Oncol. 2019 Oct 20;37(30):2769-2777. doi: 10.1200/JCO.18.01972. Epub 2019 Aug 26.
pmid
31449468
type
DERIVED
citation
Dix DB, Seibel NL, Chi YY, Khanna G, Gratias E, Anderson JR, Mullen EA, Geller JI, Kalapurakal JA, Paulino AC, Perlman EJ, Ehrlich PF, Malogolowkin M, Gastier-Foster JM, Wagner E, Grundy PE, Fernandez CV, Dome JS. Treatment of Stage IV Favorable Histology Wilms Tumor With Lung Metastases: A Report From the Children's Oncology Group AREN0533 Study. J Clin Oncol. 2018 Jun 1;36(16):1564-1570. doi: 10.1200/JCO.2017.77.1931. Epub 2018 Apr 16.
pmid
29659330
type
DERIVED