A Study Using Risk Factors to Determine Treatment for Children With Favorable Histology Wilms Tumors (FHWT)
Risk Adapted Treatment of Unilateral Favorable Histology Wilms Tumors (FHWT)
3 other identifiers
interventional
1,656
3 countries
159
Brief Summary
This phase III trial studies using risk factors in determining treatment for children with favorable tissue (histology) Wilms tumors (FHWT). Wilms Tumor is the most common type of kidney cancer in children, and FHWT is the most common subtype. Previous large clinical trials have established treatment plans that are likely to cure most children with FHWT, however some children still have their cancer come back (called relapse) and not all survive. Previous research has identified features of FHWT that are associated with higher or lower risks of relapse. The term "risk" refers to the chance of the cancer coming back after treatment. Using results of tumor histology tests, biology tests, and response to therapy may be able to improve treatment for children with FHWT.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Apr 2025
Longer than P75 for phase_3
159 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 2, 2024
CompletedFirst Posted
Study publicly available on registry
May 6, 2024
CompletedStudy Start
First participant enrolled
April 15, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 13, 2031
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 13, 2031
May 5, 2026
March 1, 2026
5.8 years
May 2, 2024
May 1, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Event-free survival (EFS)
Kaplan-Meier method will be used to estimate 4-year EFS, defined as the time from randomization or first diagnostic nephrectomy or biopsy until relapse or disease progression, secondary malignancy, or death.
Up to 4 years from study entry
Secondary Outcomes (1)
Overall survival (OS)
Up to 4 years from study entry
Study Arms (48)
Stage I, Arm I (EE-4A)
EXPERIMENTALPatients receive regimen EE-4A: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 1-7 and vincristine IV on days 1, 8, \& 15 of cycles 1-3 and day 1 of cycles 4-7. Treatment repeats every 21 days for 7 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage I, Arm II (observation)
EXPERIMENTALPatients undergo observation without chemotherapy on study with ultrasounds and x-rays.
Stage I, Arm III (DD-4A)
EXPERIMENTALPatients receive regimen DD-4A: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 1, 3, 5, 7, \& 9, vincristine IV on days 1, 8, \& 15 of cycles 1-3 and day 1 of cycles 4-9, doxorubicin IV over 3-15 minutes on day 1 of cycles 2, 4, 6, \& 8. Treatment repeats every 21 days for 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage I, Arm IV (UH-3)
EXPERIMENTALPatients receive regimen UH-3: Vincristine IV on days 1, 8, \& 15 of cycles 1, 5, 7, 10, \& 13, and days 1 \& 8 of cycles 3, 4, 8, \& 11, doxorubicin IV 3-15 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, cyclophosphamide IV over 30-60 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, and days 1-4 of cycles 2, 6, 9, 12, \& 14, carboplatin IV over 15-60 minutes on day 1 of cycles 2, 6, 9, 12, and 14, etoposide IV over 60-120 minutes on days 1-4 of cycles 2, 6, 9, 12, \& 14, and irinotecan IV over 90 minutes on days 1-5 of cycles 3, 4, 8, \& 11. Treatment repeats every 21 days for 14 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage II, Arm I (EE-4A)
EXPERIMENTALPatients receive one cycle of regimen EE-4A as in STAGE I FHWT Arm I. Patients receive cycles 2-7 of regimen EE-4A as in STAGE I FHWT Arm I. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage II, Arm II (EE-4A, VIVA)
EXPERIMENTALPatients receive one cycle of regimen EE-4A as in STAGE I FHWT Arm I. Patients receive cycles 2-9 of regimen VIVA: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 5, 7, \& 9, vincristine IV on days 1, 8, \& 15 of cycles 2-3 and day 1 of cycles 4-9, irinotecan IV over 90 minutes daily on days 1-5 of cycles 2, 4, 6, \& 8. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage II, Arm III (EE-4A, DD-4A)
EXPERIMENTALPatients receive one cycle of regimen EE-4A as in STAGE I FHWT Arm I. Patients receive cycles 2-9 of regimen DD-4A: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 5, 7, and 9, vincristine IV on days 1, 8, and 15 of cycles 2-3 and day 1 of cycles 4-9, and doxorubicin IV over 3-15 minutes on day 1 of cycles 2, 4, 6, \& 8. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm I (DD-4A, EE-4A)
EXPERIMENTALPatients able to undergo an upfront nephrectomy receive cycle 1 treatment of regimen DD-4A: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycle 1, vincristine IV on days 1, 8, \& 15 of cycle 1. Patients with standard biology receive cycles 2-7 of regimen EE-4A as in STAGE I FHWT Arm I. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm I-Upfront/Delayed (DD-4A, EE-4A)
EXPERIMENTALPatients receive cycles 1-2 of regimen DD-4A: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycle 1, vincristine IV on days 1, 8, and 15 of cycles 1-2, and doxorubicin IV over 3-15 minutes on day 1 of cycle 2. Patients with standard biology and low intermediate risk histology receive cycles 3-7 of regimen EE-4A as in STAGE I FHWT Arm I above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm II (DD-4A)
EXPERIMENTALPatients able to undergo an upfront nephrectomy receive cycle 1 treatment of regimen DD-4A: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycle 1, vincristine IV on days 1, 8, \& 15 of cycle 1. Patients with adverse biology receive cycle 2 treatment of regimen DD-4A as in STAGE II FHWT Arm III above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm II-Upfront/Delayed (DD-4A, UH-3)
EXPERIMENTALPatients receive cycles 1-2 of regimen DD-4A: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycle 1, vincristine IV on days 1, 8, and 15 of cycles 1-2, and doxorubicin IV over 3-15 minutes on day 1 of cycle 2. Patients receive regimen UH-3 as in STAGE I FHWT Arm IV above: Vincristine IV on days 1, 8, \& 15 of cycles 1, 5, 7, 10, \& 13, and days 1 \& 8 of cycles 3, 4, 8, \& 11, doxorubicin IV 3-15 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, cyclophosphamide IV over 30-60 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, and days 1-4 of cycles 2, 6, 9, 12, \& 14, carboplatin IV over 15-60 minutes on day 1 of cycles 2, 6, 9, 12, and 14, etoposide IV over 60-120 minutes on days 1-4 of cycles 2, 6, 9, 12, \& 14, and irinotecan IV over 90 minutes on days 1-5 of cycles 3, 4, 8, \& 11. Treatment repeats every 21 days for 14 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm IIA (MVI)
EXPERIMENTALPatients receive regimen MVI: Vincristine IV on days 1, 8, \& 15 of cycle 3, days 8 \& 15 of cycle 4, and day 1 of cycles 5 \& 7-13, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, doxorubicin IV over 3-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 4 and 6, irinotecan IV over 90 minutes daily on days 1-5 of cycles 5, 8, 10 \& 12, and etoposide IV over 60-120 minutes daily on days 1-5 of cycles 4 and 6. Treatment repeats every 21 days for 11 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm IIB (M)
EXPERIMENTALPatients receive regimen M: Cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, etoposide IV over 60-120 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, vincristine IV on days 8 \& 15 of cycles 3 \& 4 and day 1 of cycles 5, 6, 8, 10, \& 11, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 5, 6, 8, 10, \& 11, and doxorubicin IV over 3-15 minutes of cycles 5, 6, 8, 10, \& 11.
Stage III, Arm III-Upfront/Delayed (DD-4A, MVI)
EXPERIMENTALPatients receive cycles 1-2 of regimen DD-4A: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycle 1, vincristine IV on days 1, 8, and 15 of cycles 1-2, and doxorubicin IV over 3-15 minutes on day 1 of cycle 2. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients receive regimen MVI as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm IV-Upfront/Delayed (DD-4A, M)
EXPERIMENTALPatients receive cycles 1-2 of regimen DD-4A: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycle 1, vincristine IV on days 1, 8, and 15 of cycles 1-2, and doxorubicin IV over 3-15 minutes on day 1 of cycle 2. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients receive regimen M as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm IX-Upfront/Delayed (MVI)
EXPERIMENTALPatients receive cycles 5-13 (or 4-13 if nephrectomy occurred after cycle 3) of regimen MVI as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm V-Upfront/Delayed (DD-4A)
EXPERIMENTALPatients receive cycles 1-2 of regimen DD-4A: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycle 1, vincristine IV on days 1, 8, and 15 of cycles 1-2, and doxorubicin IV over 3-15 minutes on day 1 of cycle 2. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients receive cycles 3-4 of regimen DD-4A as in STAGE II FHWT Arm III above. They then undergo delayed nephrectomy after cycle 3 or 4. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm VA-Upfront/Delayed (DD-4A)
EXPERIMENTALPatients receive cycles 5-9 (or 4-9 if nephrectomy occurred after cycle 3) of regimen DD-4A as in STAGE II FHWT Arm III above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm VB-Upfront/Delayed (M)
EXPERIMENTALPatients receive cycles 5-9 (or 4-9 if nephrectomy occurred after cycle 3) of regimen M as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm VI-Upfront/Delayed (DD-4A, MVI)
EXPERIMENTALPatients receive cycles 1-2 of regimen DD-4A: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycle 1, vincristine IV on days 1, 8, and 15 of cycles 1-2, and doxorubicin IV over 3-15 minutes on day 1 of cycle 2. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients receive cycles 3-4 of regimen MVI as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm VII-Upfront/Delayed (DD-4A, M)
EXPERIMENTALPatients receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive cycles 3-4 of regimen M as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm VIII-Upfront/Delayed (UH-3)
EXPERIMENTALPatients receive regimen UH-3 as in STAGE I FHWT Arm IV above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm X-Upfront/Delayed (M)
EXPERIMENTALPatients receive cycles 5-11 (or 4-11 if nephrectomy occurred after cycle 3) of regimen M as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm I-Upfront-Delayed (DD-4A, EE-4A)
EXPERIMENTALPatients receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive cycles 3-9 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arms V and VA above.Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm II-Upfront-Delayed (DD-4A, UH-3)
EXPERIMENTALPatients receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive regimen UH-3 as in STAGE I FHWT Arm IV above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm III-Upfront-Delayed (DD-4A, MVI)
EXPERIMENTALPatients in Stage IV Arm III Upfront-Delayed receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive regimen MVI as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm IV-Upfront-Delayed (DD-4A, M)
EXPERIMENTALPatients in Stage IV Arm IV Upfront-Delayed receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive regimen M as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm IX-Upfront-Delayed (MVI)
EXPERIMENTALPatients in Stage IV Arm IX Upfront-Delayed continue cycles 5-13 (or 4-13 if nephrectomy occurred after cycle 3) of regimen MVI as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm V-Upfront-Delayed (DD-4A)
EXPERIMENTALPatients receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients continue with regimen DD4A for up to 4 cycles, until time of delayed nephrectomy after cycle 3 or 4 of regimen DD-4A as in STAGE II FHWT Arm II above. They then undergo delayed nephrectomy after cycle 3 or 4. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm VA-Upfront-Delayed (DD-4A)
EXPERIMENTALPatients receive cycles 5-9 (or 4-9 if nephrectomy occurred after cycle 3) of regimen DD-4A as in STAGE II FHWT Arm II above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm VB-Upfront-Delayed (M)
EXPERIMENTALPatients receive regimen M as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm VI-Upfront-Delayed (DD-4A, MVI)
EXPERIMENTALPatients receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients continue with regimen MVI for up to 4 cycles, until time of delayed nephrectomy after cycles 3 or 4 of regimen MVI as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm VII-Upfront-Delayed (DD-4A, M)
EXPERIMENTALPatients in Stage IV Arm VII Upfront-Delayed receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients continue with regimen M for up to 4 cycles, until time of delayed nephrectomy after cycles 3 or 4 of regimen M as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm VIII-Upfront-Delayed (UH-3)
EXPERIMENTALPatients in Stage IV Arm VIII Upfront-Delayed receive regimen UH-3 as in STAGE I FHWT Arm IV above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm X-Upfront-Delayed (M)
EXPERIMENTALPatients continue cycles 5-11 (or 4-11 if nephrectomy occurred after cycle 3) of regimen M as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Extrapulmonary Arm I (DD-4A, MVI)
EXPERIMENTALPatients in Stage IV Extrapulmonary Arm I receive 2 cycles of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive regimen MVI as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may undergo bone scan and/or PET.
Stage IV Extrapulmonary Arm II (DD-4A, M)
EXPERIMENTALPatients in Stage IV Extrapulmonary Arm II receive 2 cycles of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive regimen M as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may undergo bone scan and/or PET.
Stage IV Extrapulmonary Arm III (DD-4A, MVI)
EXPERIMENTALPatients in Stage IV Extrapulmonary Arm III receive 2 cycles of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive regimen MVI as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may undergo bone scan and/or PET.
Stage IV Extrapulmonary Arm IV (DD-4A, M)
EXPERIMENTALPatients in Stage IV Extrapulmonary Arm IV receive 2 cycles of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive regimen M as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may undergo bone scan and/or PET.
Stage IV Extrapulmonary Arm IX (MVI)
EXPERIMENTALPatients in Stage IV Extrapulmonary Arm IX receive cycles 5-13 (or 4-13 if nephrectomy occurred after cycle 3) of regimen MVI as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may undergo bone scan and/or PET.
Stage IV Extrapulmonary Arm V (DD-4A, UH-3)
EXPERIMENTALPatients in Stage IV Extrapulmonary Arm V receive 2 cycles of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive regimen UH-3 as in STAGE I FHWT Arm IV above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may undergo bone scan and/or PET.
Stage IV Extrapulmonary Arm VI (DD-4A, MVI)
EXPERIMENTALPatients in Stage IV Extrapulmonary Arm VI receive 2 cycles of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive cycles 3-4 of regimen MVI as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may undergo bone scan and/or PET.
Stage IV Extrapulmonary Arm VII (DD-4A, M)
EXPERIMENTALPatients in Stage IV Extrapulmonary Arm VII receive 2 cycles of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive cycles 3-4 of regimen M as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may undergo bone scan and/or PET.
Stage IV Extrapulmonary Arm VIII (UH-3)
EXPERIMENTALPatients in Stage IV Extrapulmonary Arm VIII receive regimen UH-3 as in STAGE I FHWT Arm IV above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may undergo bone scan and/or PET.
Stage IV Extrapulmonary Arm X (M)
EXPERIMENTALPatients in Stage IV Extrapulmonary Arm X receive cycles 5-11 (or 4-11 if nephrectomy occurred after cycle 3) of regimen M as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may undergo bone scan and/or PET.
Stage IV Lung Metastases Arm I (DD-4A)
EXPERIMENTALPatients receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients with standard biology and rapid complete lung response receive cycles 3-9 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arms V and VA above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Lung Metastases Arm II (DD-4A, MVI)
EXPERIMENTALPatients receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive regimen MVI as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Lung Metastases Arm III (DD-4A, M)
EXPERIMENTALPatients receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive regimen M as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Interventions
Undergo bone scan for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Given IV
Given IV
Given IV
Undergo CT
Given IV
Given IV
Given IV
Undergo MRI
Undergo nephrectomy
Undergo observation after nephrectomy
Undergo PET for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Undergo ultrasound
Given IV
Undergo X-ray
Eligibility Criteria
You may qualify if:
- Patients must be enrolled on APEC14B1 and consent to Part A - Eligibility Screening prior to enrollment on AREN2231.
- Patients must be \< 30 years old at enrollment.
- Patients with newly diagnosed Stage I-IV Favorable Histology Wilms Tumor confirmed by central review and with a qualifying Initial Stratum Assignment on APEC14B1.
- Patients must receive a qualifying Initial Stratum Assignment on APEC14B1-REN by Day 14 post-diagnostic procedure (nephrectomy or biopsy), where that procedure is Day 0.
- Patients must enroll on AREN2231 by Day 14.
- Exceptions: If patient reaches Day 14 (post initial diagnostic nephrectomy or biopsy) without receiving an Initial Stratum Assignment on APEC14B1-REN, patient will not be eligible for enrollment on AREN2231 unless all required materials (reports and Case Report Forms and specimens) for an Initial Stratum Assignment arrived by Day 7, but an Initial Stratum Assignment was not completed by Day 14. In these circumstances, after obtaining appropriate protocol consent, the patient may proceed with treatment according to local institutional staging and enroll within 5 calendar days of notification of the central Initial Stratum Assignment being issued, only if the AREN2231 Initial Stratum Assignment is in agreement with any treatment already initiated. If the Initial Stratum Assignment is not in agreement with the local institution's assessment then the patient will be ineligible for AREN2231.
- All sites must have sent or plan to send diagnostic tumor sample for molecular testing through a Clinical Laboratory Improvement Act (CLIA)-certified (or equivalent if outside of the United States \[US\]) laboratory that can detect Loss of Heterozygosity (LOH) of chromosome 1p AND 16q, and gain of chromosome 1q. Patients potentially eligible for mVLR must also have LOH of chromosome 11p15 included.
- Note: Patients are eligible for enrollment prior to obtaining these molecular testing results, and it is strongly recommended that patients are enrolled before these results are available. However, molecular results must be returned and uploaded to APEC14B1-REN for integration into risk stratification by the required timepoints (specific timelines vary by treatment arm). Patients who do not have molecular results available by the arm-specific timepoints may be taken off protocol therapy.
- Patients who have an upfront nephrectomy must have at least one lymph node sampled and confirmed as a lymph node by central pathology review to be eligible.
- Note: Lymph node sampling will also be required at delayed nephrectomy. Patients who do not have a lymph node sampled and confirmed as a lymph node by central pathology review at delayed nephrectomy will be taken off protocol therapy.
- 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.
- ONLY TO PATIENTS WHO WILL RECEIVE CHEMOTHERAPY: Serum total bilirubin ≤ 1.5 X upper limit of normal (ULN) OR direct bilirubin ≤ 3X ULN for subjects with total bilirubin levels \> 1.5 ULN (within 7 days prior to enrollment).
- ONLY TO PATIENTS WHO WILL RECEIVE CHEMOTHERAPY: Aspartate aminotransferase (AST/serum glutamate oxaloacetic transaminase \[SGOT\]) OR alanine transaminase (ALT/serum glutamic pyruvate transaminase \[SGPT\]) ≤ 3X ULN OR ≤ 5 X ULN for patients with liver metastases (within 7 days prior to enrollment).
- ONLY TO PATIENTS WHO WILL RECEIVE CHEMOTHERAPY: Shortening fraction of ≥ 27% by echocardiogram, or ejection fraction of ≥ 50% (within 7 days prior to enrollment)
- Note: This criteria only applies to patients centrally classified as Stage IV. Stage II and III patients subsequently assigned to a doxorubicin arm will be off protocol therapy if they do not meet this criteria at time of cardiac function assessment.
- +3 more criteria
You may not qualify if:
- Patient with a diagnosis of Stage V Bilateral Wilms Tumor.
- Patients who in the opinion of the investigator are not able to comply with the study procedures are not eligible.
- Patients with any uncontrolled, intercurrent illness including but not limited to symptomatic congestive heart failure.
- Patients with Stage I FHWT with a known or suspected Wilms Tumor predisposition syndrome or condition (contralateral nephrogenic rests and/or unilateral multicentric tumors) are excluded from treatment on the mVLR (Nephrectomy Only) arm.
- Notes:
- In the context of the renal tumor protocols, multicentric tumors and multifocal tumors are equivalent terms, and refer to the occurrence of two or more tumors arising within one kidney.
- Patients \< 4 years with Stage I FHWT other than epithelial subtype AND
- Stage I patients of any age with Epithelial WT
- WT Predisposition Syndromes: Beckwith Wiedemann Spectrum, Denys Drash, Trisomy 18, Idiopathic Hemihypertrophy/Isolated Lateralized Overgrowth, WAGR, Simpson-Golabi-Behmel, Bohring-Opitz, or other conditions considered by treating physician to predispose to WT.
- WT Predisposing Conditions:
- A unilateral WT and (radiologic or pathologic) determination of contralateral nephrogenic rest(s) AND/OR
- Unilateral multicentric WT
- Patients treated with partial nephrectomy at initial diagnosis are excluded from mVLR (Nephrectomy Only) arm.
- Patients with lung metastases as the only metastatic site who already had complete resection of all radiologically evident lung nodules, and have at least one nodule confirmed pathologically as tumor.
- Please note: Those with lung metastases as the only metastatic site who have complete resection of all radiologically evident lung nodules after enrollment but prior to the lung imaging following Cycle 2 of DD-4A will be inevaluable for lung assessment and subsequent stratum assignment and will, therefore, come off protocol therapy.
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (159)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
USA Health Strada Patient Care Center
Mobile, Alabama, 36604, United States
Providence Alaska Medical Center
Anchorage, Alaska, 99508, United States
Banner Children's at Desert
Mesa, Arizona, 85202, United States
Phoenix Childrens Hospital
Phoenix, Arizona, 85016, United States
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591, United States
Kaiser Permanente Downey Medical Center
Downey, California, 90242, United States
Loma Linda University Medical Center
Loma Linda, California, 92354, United States
Miller Children's and Women's Hospital Long Beach
Long Beach, California, 90806, United States
Cedars-Sinai Medical Center
Los Angeles, California, 90048, United States
Valley Children's Hospital
Madera, California, 93636, United States
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609, United States
Kaiser Permanente-Oakland
Oakland, California, 94611, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Rady Children's Hospital - San Diego
San Diego, California, 92123, United States
UCSF Medical Center-Mission Bay
San Francisco, California, 94158, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado, 80218, United States
Connecticut Children's Medical Center
Hartford, Connecticut, 06106, United States
Yale University
New Haven, Connecticut, 06520, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Broward Health Medical Center
Fort Lauderdale, Florida, 33316, United States
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908, United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida, 33021, United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
Nicklaus Children's Hospital
Miami, Florida, 33155, United States
Arnold Palmer Hospital for Children
Orlando, Florida, 32806, United States
Nemours Children's Hospital
Orlando, Florida, 32827, United States
Nemours Children's Clinic - Pensacola
Pensacola, Florida, 32504, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607, United States
Saint Mary's Medical Center
West Palm Beach, Florida, 33407, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329, United States
Augusta University Medical Center
Augusta, Georgia, 30912, United States
Atrium Health Navicent
Macon, Georgia, 31201, United States
Memorial Health University Medical Center
Savannah, Georgia, 31404, United States
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826, United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611, United States
University of Illinois
Chicago, Illinois, 60612, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Advocate Children's Hospital-Oak Lawn
Oak Lawn, Illinois, 60453, United States
Advocate Children's Hospital-Park Ridge
Park Ridge, Illinois, 60068, United States
Saint Jude Midwest Affiliate
Peoria, Illinois, 61637, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
Blank Children's Hospital
Des Moines, Iowa, 50309, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
Children's Hospital New Orleans
New Orleans, Louisiana, 70118, United States
Ochsner Medical Center Jefferson
New Orleans, Louisiana, 70121, United States
Maine Children's Cancer Program
Scarborough, Maine, 04074, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201, United States
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Baystate Medical Center
Springfield, Massachusetts, 01199, United States
UMass Memorial Medical Center - University Campus
Worcester, Massachusetts, 01655, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
Children's Hospital of Michigan
Detroit, Michigan, 48201, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503, United States
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
University of Missouri Children's Hospital
Columbia, Missouri, 65212, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108, United States
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada, 89135, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Morristown Medical Center
Morristown, New Jersey, 07960, United States
Jersey Shore Medical Center
Neptune City, New Jersey, 07753, United States
Saint Peter's University Hospital
New Brunswick, New Jersey, 08901, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903, United States
Newark Beth Israel Medical Center
Newark, New Jersey, 07112, United States
Albany Medical Center
Albany, New York, 12208, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
NYU Langone Hospital - Long Island
Mineola, New York, 11501, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, 11040, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
University of Rochester
Rochester, New York, 14642, United States
Stony Brook University Medical Center
Stony Brook, New York, 11794, United States
State University of New York Upstate Medical University
Syracuse, New York, 13210, United States
New York Medical College
Valhalla, New York, 10595, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203, United States
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, 28204, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
East Carolina University
Greenville, North Carolina, 27834, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106, United States
Dayton Children's Hospital
Dayton, Ohio, 45404, United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio, 43606, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Legacy Emanuel Children's Hospital
Portland, Oregon, 97227, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Geisinger Medical Center
Danville, Pennsylvania, 17822, United States
Penn State Children's Hospital
Hershey, Pennsylvania, 17033, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
Rhode Island Hospital
Providence, Rhode Island, 02903, United States
Prisma Health Richland Hospital
Columbia, South Carolina, 29203, United States
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134, United States
T C Thompson Children's Hospital
Chattanooga, Tennessee, 37403, United States
East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916, United States
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
Texas Tech University Health Sciences Center-Amarillo
Amarillo, Texas, 79106, United States
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723, United States
Driscoll Children's Hospital
Corpus Christi, Texas, 78411, United States
Medical City Dallas Hospital
Dallas, Texas, 75230, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
Cook Children's Medical Center
Fort Worth, Texas, 76104, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
Covenant Children's Hospital
Lubbock, Texas, 79410, United States
UMC Cancer Center / UMC Health System
Lubbock, Texas, 79415, United States
Children's Hospital of San Antonio
San Antonio, Texas, 78207, United States
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229, United States
Primary Children's Hospital
Salt Lake City, Utah, 84113, United States
University of Vermont and State Agricultural College
Burlington, Vermont, 05405, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
Inova Fairfax Hospital
Falls Church, Virginia, 22042, United States
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
Carilion Children's
Roanoke, Virginia, 24014, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204, United States
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, 98405, United States
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, 54301, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Queensland Children's Hospital
South Brisbane, Queensland, 4101, Australia
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8, Canada
University of Alberta Hospital
Edmonton, Alberta, T6G 2B7, Canada
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9, Canada
IWK Health Centre
Halifax, Nova Scotia, B3K 6R8, Canada
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, L8N 3Z5, Canada
Children's Hospital
London, Ontario, N6A 5W9, Canada
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H 8L1, Canada
Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, H3H 1P3, Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5, Canada
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
Sherbrooke, Quebec, J1H 5N4, Canada
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
Québec, G1V 4G2, Canada
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Elizabeth A Mullen
Children's Oncology Group
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 2, 2024
First Posted
May 6, 2024
Study Start
April 15, 2025
Primary Completion (Estimated)
February 13, 2031
Study Completion (Estimated)
February 13, 2031
Last Updated
May 5, 2026
Record last verified: 2026-03