A Study Using Risk Factors to Determine Treatment for Children With Favorable Histology Wilms Tumors (FHWT)
NCT ID: NCT06401330
Last Updated: 2026-01-23
Study Results
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Basic Information
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RECRUITING
PHASE3
1656 participants
INTERVENTIONAL
2025-04-15
2031-02-13
Brief Summary
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Detailed Description
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I. To maintain event-free survival (EFS) for Stage I favorable histology Wilms tumor (FHWT) patients without adverse biology who are also (1) 2 to \< 4 years of age, OR (2) age \< 2 years with tumor weight of 550 grams or more, OR (3) age 4+ years with epithelial histology subtype while reducing post-nephrectomy therapy from vincristine, actinomycin (EE-4A) to Nephrectomy Only. (Stage I Nephrectomy Only Stratum 2) II. To improve EFS for Stage I FHWT patients with age \< 2 years AND nephrectomy weight \< 550g AND whose tumors have adverse biology by treating with EE-4A instead of Nephrectomy Only. (Stage I EE-4A Stratum 3) III. To evaluate whether addition of vincristine and irinotecan to standard EE-4A (novel vincristine, actinomycin, irinotecan \[Regimen VIVA\]) is non-inferior to vincristine, actinomycin, doxorubicin (DD-4A) in terms of EFS among Stage II FHWT patients whose tumors demonstrate adverse biology. (Stage II: VIVA versus \[vs\] DD-4A Randomization) IV. To evaluate whether omission of doxorubicin (EE-4A) is non-inferior to historical DD-4A in Stage III FHWT patients with standard biology or post-therapy blastemal predominance. (Stage III: EE-4A) V. To demonstrate the non-inferiority of vincristine, actinomycin, doxorubicin, cyclophosphamide, etoposide and irinotecan (Regimen MVI) to vincristine, dactinomycin, doxorubicin, cyclophosphamide and etoposide (Regimen M) in the treatment of Stage III FHWT patients whose tumors exhibit adverse biology (post-chemotherapy blastemal predominance excluded). (Stage III: Regimen MVI vs Regimen M Randomization) VI. To demonstrate the non-inferiority of Regimen MVI to Regimen M in the treatment of Stage IV FHWT patients with adverse biology, slow incomplete lung response (SIR), or extrapulmonary metastases (EPM) (post-therapy blastemal predominance excluded). (Stage IV: Regimen MVI vs Regimen M Randomization) VII. To demonstrate the superiority of vincristine, doxorubicin, cyclophosphamide, etoposide, carboplatin and irinotecan (Regimen UH-3) vs historical DD-4A or Regimen M in treatment of Stage III or IV FHWT patients with blastemal predominance at delayed nephrectomy. (Stage III-IV: UH-3 \[Blastemal Predominance\])
SECONDARY OBJECTIVES:
I. To describe outcomes for Stage I FHWT patients without adverse biology who are either less than 4 years of age OR 4+ years of age with epithelial subtype who are treated with Nephrectomy Only and assess consistency with a matched historical control from the prior Children's Oncology Group (COG) therapeutic era. (Stage I: Nephrectomy Only) II. To describe outcomes for Stage I FHWT patients with adverse biology OR age \> 4 and not epithelial subtype who are treated with post-nephrectomy EE-4A and assess consistency with a matched historical control from the prior COG therapeutic era. (Stage I: EE-4A) III. To describe overall survival in the cohort of modified very low risk (mVLR) patients who relapse following treatment with nephrectomy only and are assigned at relapse to DD-4A (if presumed or confirmed favorable histology Wilms tumor at relapse) or UH-3 (if evidence of anaplasia at relapse). (Stage I: Nephrectomy Only Relapse) IV. To describe outcomes for Stage II FHWT patients without adverse biology who are treated with post-nephrectomy EE-4A and assess consistency with a matched historical control from the prior COG therapeutic era. (Stage II: EE-4A) V. To compare outcomes of Stage II FHWT patients whose tumors are negative for combined loss of heterozygosity (LOH) but positive for 1q gain who are randomized to VIVA vs DD-4A on AREN2231 against historically matched patients treated with EE-4A during the prior COG therapeutic era. (Stage II VIVA vs DD-4A Stratum 1) VI. To compare outcomes of Stage II FHWT patients whose tumors are positive for combined LOH 1p AND 16q and who are randomized to VIVA vs DD-4A on AREN2231 against historically matched patients treated with DD-4A during the prior COG therapeutic era. (Stage II VIVA vs DD-4A Stratum 2) VII. To compare outcomes of Stage III FHWT patients whose tumors have adverse biology other than combined LOH and who are randomized to Regimen MVI vs Regimen M on AREN2231 against historically matched patients treated with DD-4A during the prior COG therapeutic era (post-chemotherapy blastemal predominance excluded). (Stage III Regimen MVI vs Regimen M Stratum 1) VIII. To compare outcomes of Stage III FHWT patients whose tumors have combined LOH and who are randomized to Regimen MVI vs Regimen M on AREN2231 against historically matched patients treated with Regimen M during the prior COG therapeutic era (post-chemotherapy blastemal predominance excluded). (Stage III Regimen MVI vs Regimen M Stratum 2) IX. To describe outcomes for Stage IV FHWT patients with rapid complete response of lung only metastases and no adverse biology who are treated with DD-4A on AREN2231 and assess consistency with a matched historical control from the prior COG therapeutic era (post-chemotherapy blastemal predominance excluded). (Stage IV: DD-4A) X. To compare outcomes of Stage IV lung only patients with either combined LOH 1p AND 16q or SIR who are randomized to Regimen MVI vs Regimen M on AREN2231 against historically matched patients treated with Regimen M during the prior COG therapeutic era (post-chemotherapy blastemal predominance excluded). (Stage IV Regimen MVI vs Regimen M Stratum 1) XI. To compare outcomes of Stage IV lung only rapid complete response (RCR) patients without combined LOH 1p AND 16q who are positive for other adverse biological factors and who are randomized to Regimen MVI vs Regimen M on AREN2231 against historically matched patients treated with DD-4A during the prior COG therapeutic era (post-chemotherapy blastemal predominance excluded). (Stage IV Regimen MVI vs Regimen M Stratum 2) XII. To compare outcomes of Stage IV patients with extrapulmonary metastases (EPM) who are randomized to Regimen MVI vs Regimen M on AREN2231 against historically matched patients treated with Regimen M during the prior COG therapeutic era (post-chemotherapy blastemal predominance excluded). (Stage IV Regimen MVI vs Regimen M Stratum 3) XIII. To report a pooled comparison of Regimen MVI vs Regimen M in Stage III or Stage IV randomized patients. (Stage III-IV Regimen MVI vs Regimen M) XIV. To compare outcomes of Stage III or IV FHWT patients with blastemal predominance at delayed nephrectomy who are treated with Regimen UH-3 on AREN2231 vs a historically matched cohort that received DD-4A in the prior COG therapeutic era. (Stage III-IV UH-3 Stratum 1) XV. To compare outcomes of Stage III or IV FHWT patients with blastemal predominance at delayed nephrectomy who are treated with Regimen UH-3 on AREN2231 vs a historically matched cohort that received Regimen M in the prior COG therapeutic era. (Stage III-IV UH-3 Stratum 2) XVI. To describe outcomes of Stage III or IV FHWT patients with delayed nephrectomy occurring after the start of Cycles 3 or 4 (super delayed) who are assigned to Regimen M or continued DD4A. (Stage III-IV Super Delayed Nephrectomy)
EXPLORATORY OBJECTIVES:
I. To determine the impact of imaging schedule and modality (chest x-ray \[CXR\], ultrasound \[US\], versus computed tomography/magnetic resonance imaging \[CT/MRI\], versus clinical symptoms) on relapse, timing of detection of relapse, burden of disease at relapse (as assessed by retrospective central imaging review), as well as impact on survival.
II. To analyze the impact of radiologically determined pulmonary tumor burden on outcomes.
III. To assess whether imaging modality (ultrasound, CT, MRI with or without hepatocyte specific contrast agent) at diagnosis is associated with detection of increased number of liver metastases, and whether modality choice impacts surgery and/or radiation planning for liver metastases.
IV. To accurately describe the responses of extrapulmonary metastases to the various therapeutic modalities (chemotherapy, radiation therapy, and surgery) through central review of institutional imaging at various stages of treatment, and to correlate institutionally interpreted radiologic response interpretations with central review.
V. To describe the association of the number of anatomically relevant and pathologically confirmed lymph nodes sampled and percent of positive lymph nodes (LNs) on EFS and overall survival (OS).
VI. To document the surgical and/or medical rationale and approach for biopsy (including type of biopsy, number of biopsies, and site of biopsy) for all patients who are treated with the approach of initial biopsy and delayed nephrectomy.
VII. To describe sites of recurrence for patients with liver metastases according to the surgery and/or radiation therapy administered for residual liver lesions at Week 6 and 12.
VIII. To increase the number of patients eligible to avoid lung radiation therapy (RT) by encouraging resection of residual pulmonary nodules for patients defined as Stage IV FHWT with standard biology and who have 1-3 residual pulmonary nodules on imaging after Cycle 2, by omitting lung RT for those who are found to have no viable tumor in resected nodules.
IX. To describe whether residual lung lesions at end of therapy are associated with relapse.
X. To improve the reliability of data derived from central surgical review through the implementation of a standardized operative note.
XI. To describe the treatment, perioperative morbidity and outcome of patients noted to have inferior vena cava (IVC) tumor thrombus at time of diagnosis, including surgical approach, pathology findings and specific radiation therapy received.
XII. To determine the feasibility of employing intensity modulated radiation therapy (IMRT) and proton therapy with central quality assurance (QA) monitoring within the prescribed time frame.
XIII. To determine the lung tumor and liver tumor control rate using IMRT and/or proton therapy and compare it to standard 3-dimensional radiotherapy in the current study and the AREN0533 study.
XIV. To determine the flank and abdominal tumor control rates in children with Stage IV FHWT who received abdominal radiotherapy after 2 cycles of chemotherapy in this study (delayed abdominal radiation) and compare it to AREN0533 study where abdominal radiotherapy was performed within 2 weeks of nephrectomy (upfront abdominal radiation).
XV. To compare abdominal relapse according to protocol-recommended radiotherapy fields (flank vs. whole abdominal) in the current study and compare it to the abdominal relapse according to radiotherapy fields (flank vs. whole abdominal) in the AREN0532 and AREN0533 studies.
XVI. To determine the impact of radiotherapy on local and distant control rates for EPM sites and compare them to EPM sites not receiving radiation.
XVII. To describe the rate and severity of recurrent hepatotoxicity in patients who undergo re-introduction of chemotherapy after experiencing hepatopathy.
XVIII. To collect serial blood and urine samples to bank for future research studies.
OUTLINE:
STAGE I FHWT: Patients will have already undergone nephrectomy and lymph node sampling prior to trial enrollment. Patients \< 4 years old at diagnosis or with epithelial subtype FHWT of any age, undergo observation until tumor biomarker testing returns. Patients with adverse biology are assigned to Arm I. Patients with standard biology are assigned to Arm II and undergo observation post-nephrectomy until disease relapse. At the time of disease relapse, patients with favorable histology are assigned to Arm III, and patients with unfavorable (anaplastic) histology are assigned to Arm IV. Patients ≥ 4 years of age at diagnosis without epithelial FHWT are assigned to Arm I regardless of biology results.
* ARM I: Patients receive regimen EE-4A: Dactinomycin intravenously (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.
* ARM II: Patients undergo observation without chemotherapy on study with ultrasounds and x-rays.
* ARM III: Patients 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.
* ARM IV: Patients 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.
STAGE II FHWT: Patients receive one cycle of regimen EE-4A as in STAGE I FHWT Arm I. Patients with standard biology are assigned to Arm I below. Patients with adverse biology are randomized to Arm II or Arm III below.
* ARM I: Patients receive cycles 2-7 of regimen EE-4A as in STAGE I FHWT Arm I.
* ARM II: 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.
* ARM III: 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.
STAGE III FHWT: Patients 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 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. Patients with standard biology are assigned to Arm I below. Patients with adverse biology are assigned to Arm II below.
* ARM I: Patients receive cycles 2-7 of regimen EE-4A as in STAGE I FHWT Arm I.
* ARM II: Patients receive cycle 2 treatment of regimen DD-4A as in STAGE II FHWT Arm III above. They are then randomized to Arm IIA or Arm IIB below.
* ARM IIA: Patients 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.
* ARM IIB: Patients 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. Treatment repeats every 21 days for 9 cycles in the absence of disease progression or unacceptable toxicity.
STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY): Patients 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 ABLE TO UNDERGO A DELAYED NEPHRECTOMY AFTER CYCLE 2: Patients with standard biology and low or intermediate risk histology are assigned to Arm I below. Patients with high risk histology are assigned to Arm II below. Patients with adverse biology and low or intermediate risk histology are randomized to Arm III or Arm IV below.
* PATIENTS UNABLE TO UNDERGO A DELAYED NEPHRECTOMY AFTER CYCLE 2: Patients with standard biology are assigned to Arm V below. Patients with adverse biology are randomized to Arm VI or Arm VII below.
* ARM I: Patients receive cycles 3-7 of regimen EE-4A as in STAGE I FHWT Arm I above.
* ARM II: 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.
* ARM III: Patients receive regimen MVI as in STAGE III FHWT Arm IIA above.
* ARM IV: Patients receive regimen M as in STAGE III FHWT Arm IIB above.
* ARM V: 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 with low or intermediate risk histology who still have standard biology are then assigned to Arm VA. Patients with low or intermediate risk histology with new adverse biology (positive lymph nodes, and LOH of 1p or 16q from original biopsy) are then assigned to Arm VB. Patients with high risk histology are assigned to Arm VIII below.
* ARM VA: Patients 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.
* ARM VB: Patients receive cycles 5-9 (or 4-9 if nephrectomy occurred after cycle 3) of regimen M as in STAGE III FHWT Arm IIB above.
* ARM VI: Patients receive cycles 3-4 of regimen MVI as in STAGE III FHWT Arm IIA above. Patients with high risk histology after delayed nephrectomy after cycle 3 or 4 are assigned to Arm VIII. Patients with low or intermediate risk histology after delayed nephrectomy after cycle 3 or 4 are assigned to Arm IX.
* ARM VII: Patients receive cycles 3-4 of regimen M as in STAGE III FHWT Arm IIB above. Patients with high risk histology after delayed nephrectomy after cycle 3 or 4 are assigned to Arm VIII. Patients with low or intermediate risk histology after delayed nephrectomy after cycle 3 or 4 are assigned to Arm X.
* ARM VIII: Patients receive regimen UH-3 as in STAGE I FHWT Arm IV above.
* ARM IX: Patients receive cycles 5-13 (or 4-13 if nephrectomy occurred after cycle 3) of regimen MVI as in STAGE III FHWT Arm IIA above.
* ARM X: Patients receive cycles 5-11 (or 4-11 if nephrectomy occurred after cycle 3) of regimen M as in STAGE III FHWT Arm IIB above.
STAGE IV FHWT LUNG METASTASES (UPFRONT NEPHRECTOMY): Patients 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 (RCR) are assigned to Arm I below. Patients with standard biology and slow incomplete lung response (SIR), or adverse biology (with either RCR or SIR) are randomized to Arm II or Arm III below.
* ARM I: Patients receive cycles 3-9 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arms V and VA above.
* ARM II: Patients receive regimen MVI as in STAGE III FHWT Arm IIA above.
* ARM III: Patients receive regimen M as in STAGE III FHWT Arm IIB above.
STAGE IV FHWT LUNG METASTASES (UPFRONT BIOPSY/DELAYED NEPHRECTOMY): Patients receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above.
* PATIENTS ABLE TO UNDERGO A DELAYED NEPHRECTOMY AFTER CYCLE 2: Patients with standard biology, low or intermediate risk histology, and RCR are assigned to Arm I below. Patients with high risk histology are assigned to Arm II below. Patients with adverse biology OR SIR and low or intermediate risk histology are randomized to Arm III or Arm IV below.
* PATIENTS UNABLE TO UNDERGO A DELAYED NEPHRECTOMY AFTER CYCLE 2: Patients with standard biology and RCR are assigned to Arm V below. Patients with standard biology and SIR OR adverse biology and either SIR or RCR are randomized to Arm VI or Arm VII below.
* ARM I: Patients receive cycles 3-7 of regimen EE-4A as in STAGE I FHWT Arm I above.
* ARM II: Patients receive regimen UH-3 as in STAGE I FHWT Arm IV above.
* ARM III: Patients receive regimen MVI as in STAGE III FHWT Arm IIA above.
* ARM IV: Patients receive regimen M as in STAGE III FHWT Arm IIB above.
* ARM V: Patients receive cycles 3-4 of regimen DD-4A as in STAGE II FHWT Arm II above. They then undergo delayed nephrectomy after cycle 3 or 4. Patients with low or intermediate risk histology still with standard biology are then assigned to Arm VA. Patients with low or intermediate risk histology and new adverse biology (positive lymph nodes, and LOH of 1p or 16q from original biopsy) are then assigned to Arm VB. Patients with high risk histology are assigned to Arm VIII below.
* ARM VA: Patients 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.
* ARM VB: Patients receive regimen M as in STAGE III FHWT Arm IIB above.
* ARM VI: Patients receive cycles 3-4 of regimen MVI as in STAGE III FHWT Arm IIA above. Patients with high risk histology after delayed nephrectomy in cycle 3 or 4 are assigned to Arm VIII. Patients with low or intermediate risk histology after delayed nephrectomy in cycle 3 or 4 are assigned to Arm IX.
* ARM VII: Patients receive cycles 3-4 of regimen M as in STAGE III FHWT Arm IIB above. Patients with high risk histology after delayed nephrectomy in cycle 3 or 4 are assigned to Arm VIII. Patients with low or intermediate risk histology after delayed nephrectomy in cycle 3 or 4 are assigned to Arm X.
* ARM VIII: Patients receive regimen UH-3 as in STAGE I FHWT Arm IV above.
* ARM IX: Patients receive cycles 5-13 (or 4-13 if nephrectomy occurred after cycle 3) of regimen MVI as in STAGE III FHWT Arm IIA above.
* ARM X: Patients receive cycles 5-11 (or 4-11 if nephrectomy occurred after cycle 3) of regimen M as in STAGE III FHWT Arm IIB above. NOTE: Patients who receive 4 cycles of initial treatment per regimen DD-4A omit cycle 11.
STAGE IV FHWT EXTRAPULMONARY METASTASES: Patients receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above.
PATIENTS ABLE TO UNDERGO UPFRONT NEPHRECTOMY: Patients are randomized to Arm I or II below.
PATIENTS ABLE TO UNDERGO DELAYED NEPHRECTOMY AFTER CYCLE 2: Patients with low or intermediate risk histology are randomized to Arm III or IV.
PATIENTS ABLE TO UNDERGO DELAYED NEPHRECTOMY AFTER CYCLE 2: Patients with high risk histology are assigned to Arm V.
PATIENTS UNABLE TO UNDERGO DELAYED NEPHRECTOMY AFTER CYCLE 2: Patients are randomized to Arm VI or VII.
* ARM I: Patients receive regimen MVI as in STAGE III FHWT Arm IIA above.
* ARM II: Patients receive regimen M as in STAGE III FHWT Arm IIB above.
* ARM III: Patients receive regimen MVI as in STAGE III FHWT Arm IIA above.
* ARM IV: Patients receive regimen M as in STAGE III FHWT Arm IIB above.
* ARM V: Patients receive regimen UH-3 as in STAGE I FHWT Arm IV above.
* ARM VI: Patients receive cycles 3-4 of regimen MVI as in STAGE III FHWT Arm IIA above. Patients undergoing nephrectomy after cycles 3 or 4 and with low or intermediate risk histology are assigned to Arm IX below. Patients undergoing nephrectomy after cycles 3 or 4 and with high risk histology are assigned to Arm VIII below
* ARM VII: Patients receive cycles 3-4 of regimen M as in STAGE III FHWT Arm IIB above. Patients undergoing nephrectomy after cycles 3 or 4 and with low or intermediate risk histology are assigned to Arm X below. Patients undergoing nephrectomy after cycles 3 or 4 and with high risk histology are assigned to Arm VIII below.
* ARM VIII: Patients receive regimen UH-3 as in STAGE I FHWT Arm IV above.
* ARM IX: Patients receive cycles 5-13 (or 4-13 if nephrectomy occurred after cycle 3) of regimen MVI as in STAGE III FHWT Arm IIA above.
* ARM X: Patients receive cycles 5-11 (or 4-11 if nephrectomy occurred after cycle 3) of regimen M as in STAGE III FHWT Arm IIB above.
* NOTE: Patients receiving regimens EE-4A, DD-4A, VIVA, M, MVI \& UH3 also undergo computed tomography (CT), CT or magnetic resonance imaging (MRI), ultrasound, and X-ray imaging throughout the trial. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may also undergo bone scan and/or positron emission tomography (PET).
After completion of study treatment, patients are followed for 10 years.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Stage I, Arm IV (UH-3)
Patients 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.
Carboplatin
Given IV
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Irinotecan
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage II, Arm I (EE-4A)
Patients 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.
Computed Tomography
Undergo CT
Dactinomycin
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage II, Arm II (EE-4A, VIVA)
Patients 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.
Computed Tomography
Undergo CT
Dactinomycin
Given IV
Irinotecan
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage II, Arm III (EE-4A, DD-4A)
Patients 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.
Computed Tomography
Undergo CT
Dactinomycin
Given IV
Doxorubicin
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage III, Arm I (DD-4A, EE-4A)
Patients 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 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. 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.
Computed Tomography
Undergo CT
Dactinomycin
Given IV
Doxorubicin
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage III, Arm I-Upfront/Delayed (DD-4A, EE-4A)
Patients 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 3-7 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.
Computed Tomography
Undergo CT
Dactinomycin
Given IV
Doxorubicin
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage III, Arm II (DD-4A)
Patients 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 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. 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.
Computed Tomography
Undergo CT
Dactinomycin
Given IV
Doxorubicin
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage I, Arm I (EE-4A)
Patients 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.
Computed Tomography
Undergo CT
Dactinomycin
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage I, Arm II (observation)
Patients undergo observation without chemotherapy on study with ultrasounds and x-rays.
Patient Observation
Undergo observation after nephrectomy
Ultrasound Imaging
Undergo ultrasound
X-Ray Imaging
Undergo X-ray
Stage I, Arm III (DD-4A)
Patients 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.
Computed Tomography
Undergo CT
Dactinomycin
Given IV
Doxorubicin
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage IV Arm IV-Upfront-Delayed (DD-4A, M)
Patients 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.
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage IV Arm IX-Upfront-Delayed (MVI)
Patients in Stage IV Arm IX Upfront-Delayed 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.
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Irinotecan
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage IV Arm V-Upfront-Delayed (DD-4A)
Patients 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 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.
Computed Tomography
Undergo CT
Dactinomycin
Given IV
Doxorubicin
Given IV
Magnetic Resonance Imaging
Undergo MRI
Nephrectomy
Undergo nephrectomy
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage IV Arm VA-Upfront-Delayed (DD-4A)
Patients 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.
Computed Tomography
Undergo CT
Dactinomycin
Given IV
Doxorubicin
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage IV Arm VB-Upfront-Delayed (M)
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.
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage IV Arm VI-Upfront-Delayed (DD-4A, MVI)
Patients 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 MVI as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.
Bone Scan
Undergo bone scan for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Irinotecan
Given IV
Magnetic Resonance Imaging
Undergo MRI
Positron Emission Tomography
Undergo PET for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage IV Arm VII-Upfront-Delayed (DD-4A, M)
Patients 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 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.
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage IV Arm VIII-Upfront-Delayed (UH-3)
Patients 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.
Carboplatin
Given IV
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Irinotecan
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage IV Arm X-Upfront-Delayed (M)
Patients 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.
Bone Scan
Undergo bone scan for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Magnetic Resonance Imaging
Undergo MRI
Positron Emission Tomography
Undergo PET for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage IV Extrapulmonary Arm I (DD-4A, MVI)
Patients in Stage IV Extrapulmonary Arm I 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. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may undergo bone scan and/or PET.
Bone Scan
Undergo bone scan for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Irinotecan
Given IV
Magnetic Resonance Imaging
Undergo MRI
Positron Emission Tomography
Undergo PET for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage IV Extrapulmonary Arm II (DD-4A, M)
Patients in Stage IV Extrapulmonary Arm II 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. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may undergo bone scan and/or PET.
Bone Scan
Undergo bone scan for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Magnetic Resonance Imaging
Undergo MRI
Positron Emission Tomography
Undergo PET for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage IV Extrapulmonary Arm III (DD-4A, MVI)
Patients in Stage IV Extrapulmonary Arm III 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. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may undergo bone scan and/or PET.
Bone Scan
Undergo bone scan for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Irinotecan
Given IV
Magnetic Resonance Imaging
Undergo MRI
Positron Emission Tomography
Undergo PET for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage IV Extrapulmonary Arm IV (DD-4A, M)
Patients in Stage IV Extrapulmonary Arm IV 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. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may undergo bone scan and/or PET.
Bone Scan
Undergo bone scan for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Magnetic Resonance Imaging
Undergo MRI
Positron Emission Tomography
Undergo PET for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage IV Extrapulmonary Arm IX (MVI)
Patients 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.
Bone Scan
Undergo bone scan for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Computed Tomography
Undergo CT
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Irinotecan
Given IV
Magnetic Resonance Imaging
Undergo MRI
Positron Emission Tomography
Undergo PET for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage IV Extrapulmonary Arm V (DD-4A, UH-3)
Patients 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. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may undergo bone scan and/or PET.
Bone Scan
Undergo bone scan for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Carboplatin
Given IV
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Irinotecan
Given IV
Magnetic Resonance Imaging
Undergo MRI
Positron Emission Tomography
Undergo PET for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage IV Extrapulmonary Arm VI (DD-4A, MVI)
Patients in Stage IV Extrapulmonary Arm VI 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 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.
Bone Scan
Undergo bone scan for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Irinotecan
Given IV
Magnetic Resonance Imaging
Undergo MRI
Positron Emission Tomography
Undergo PET for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage IV Extrapulmonary Arm VII (DD-4A, M)
Patients in Stage IV Extrapulmonary Arm VII 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. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may undergo bone scan and/or PET.
Bone Scan
Undergo bone scan for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Magnetic Resonance Imaging
Undergo MRI
Positron Emission Tomography
Undergo PET for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage IV Extrapulmonary Arm VIII (UH-3)
Patients 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.
Bone Scan
Undergo bone scan for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Carboplatin
Given IV
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Irinotecan
Given IV
Magnetic Resonance Imaging
Undergo MRI
Positron Emission Tomography
Undergo PET for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage IV Extrapulmonary Arm X (M)
Patients 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.
Bone Scan
Undergo bone scan for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Magnetic Resonance Imaging
Undergo MRI
Positron Emission Tomography
Undergo PET for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage IV Lung Metastases Arm I (DD-4A)
Patients 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.
Computed Tomography
Undergo CT
Dactinomycin
Given IV
Doxorubicin
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage IV Lung Metastases Arm II (DD-4A, MVI)
Patients 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.
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Irinotecan
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage IV Lung Metastases Arm III (DD-4A, MVI)
Patients 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.
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage III, Arm II-Upfront/Delayed (DD-4A, UH-3)
Patients 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.
Carboplatin
Given IV
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Irinotecan
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage III, Arm IIA (MVI)
Patients 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.
Bone Scan
Undergo bone scan for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Irinotecan
Given IV
Magnetic Resonance Imaging
Undergo MRI
Positron Emission Tomography
Undergo PET for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage III, Arm IIB (M)
Patients 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. Treatment repeats every 21 days for 9 cycles in the absence of disease progression or unacceptable toxicity.
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage III, Arm III-Upfront/Delayed (DD-4A, MVI)
Patients 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.
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Irinotecan
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage III, Arm IV-Upfront/Delayed (DD-4A, M)
Patients 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.
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage III, Arm IX-Upfront/Delayed (MVI)
Patients 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.
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Irinotecan
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage III, Arm V-Upfront/Delayed (DD-4A)
Patients 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.
Computed Tomography
Undergo CT
Dactinomycin
Given IV
Doxorubicin
Given IV
Magnetic Resonance Imaging
Undergo MRI
Nephrectomy
Undergo nephrectomy
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage III, Arm VA-Upfront/Delayed (DD-4A)
Patients 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.
Computed Tomography
Undergo CT
Dactinomycin
Given IV
Doxorubicin
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage III, Arm VB-Upfront/Delayed (M)
Patients 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.
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
X-Ray Imaging
Undergo X-ray
Stage III, Arm VI-Upfront/Delayed (DD-4A, MVI)
Patients 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.
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Irinotecan
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage III, Arm VII-Upfront/Delayed (DD-4A, M)
Patients 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.
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage III, Arm VIII-Upfront/Delayed (UH-3)
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.
Carboplatin
Given IV
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Irinotecan
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage III, Arm X-Upfront/Delayed (M)
Patients 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.
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage IV Arm I-Upfront-Delayed (DD-4A, EE-4A)
Patients receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients 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.
Computed Tomography
Undergo CT
Dactinomycin
Given IV
Doxorubicin
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage IV Arm II-Upfront-Delayed (DD-4A, UH-3)
Patients 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.
Carboplatin
Given IV
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Irinotecan
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Stage IV Arm III-Upfront-Delayed (DD-4A, MVI)
Patients 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.
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Irinotecan
Given IV
Magnetic Resonance Imaging
Undergo MRI
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Bone Scan
Undergo bone scan for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Carboplatin
Given IV
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Dactinomycin
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Irinotecan
Given IV
Magnetic Resonance Imaging
Undergo MRI
Nephrectomy
Undergo nephrectomy
Patient Observation
Undergo observation after nephrectomy
Positron Emission Tomography
Undergo PET for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Ultrasound Imaging
Undergo ultrasound
Vincristine
Given IV
X-Ray Imaging
Undergo X-ray
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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.
* 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).
* 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).
* 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.
* Known HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* All patients and/or their parents or legal guardians must sign a written informed consent.
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
Exclusion Criteria
* 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.
* Exclusion from the Nephrectomy Only arm applies to two groups of patients:
* Patients \< 4 years with Stage I FHWT other than epithelial subtype AND
* Stage I patients of any age with Epithelial WT
* For the purpose of exclusion from the Nephrectomy Only Arm, known or suspected WT predisposition syndromes or conditions are defined as follows:
* 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.
* Patients with known Charcot-Marie-Tooth syndrome.
* Patients who have had prior tumor-directed chemotherapy or radiotherapy for the current diagnosis except for therapy delivered for an emergent issue, as medically indicated.
* Patients who will potentially require doxorubicin on this study and have previously received doxorubicin for another diagnosis.
* Patients receiving concurrent chemotherapy for a different diagnosis.
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
* Lactating females who plan to breastfeed their infants.
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.
30 Years
ALL
No
Sponsors
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Children's Oncology Group
NETWORK
Responsible Party
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Principal Investigators
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Elizabeth A Mullen
Role: PRINCIPAL_INVESTIGATOR
Children's Oncology Group
Locations
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Children's Hospital of Alabama
Birmingham, Alabama, United States
Providence Alaska Medical Center
Anchorage, Alaska, United States
Banner Children's at Desert
Mesa, Arizona, United States
Phoenix Childrens Hospital
Phoenix, Arizona, United States
Arkansas Children's Hospital
Little Rock, Arkansas, United States
Loma Linda University Medical Center
Loma Linda, California, United States
Cedars Sinai Medical Center
Los Angeles, California, United States
Valley Children's Hospital
Madera, California, United States
UCSF Benioff Children's Hospital Oakland
Oakland, California, United States
Kaiser Permanente-Oakland
Oakland, California, United States
Children's Hospital of Orange County
Orange, California, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
Rady Children's Hospital - San Diego
San Diego, California, United States
UCSF Medical Center-Mission Bay
San Francisco, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
Connecticut Children's Medical Center
Hartford, Connecticut, United States
Yale University
New Haven, Connecticut, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Broward Health Medical Center
Fort Lauderdale, Florida, United States
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida, United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
Nicklaus Children's Hospital
Miami, Florida, United States
Arnold Palmer Hospital for Children
Orlando, Florida, United States
Nemours Children's Hospital
Orlando, Florida, United States
Nemours Children's Clinic - Pensacola
Pensacola, Florida, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, United States
Saint Mary's Medical Center
West Palm Beach, Florida, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, United States
Augusta University Medical Center
Augusta, Georgia, United States
Atrium Health Navicent
Macon, Georgia, United States
Memorial Health University Medical Center
Savannah, Georgia, United States
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States
University of Illinois
Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Advocate Children's Hospital-Oak Lawn
Oak Lawn, Illinois, United States
Advocate Children's Hospital-Park Ridge
Park Ridge, Illinois, United States
Saint Jude Midwest Affiliate
Peoria, Illinois, United States
Riley Hospital for Children
Indianapolis, Indiana, United States
Blank Children's Hospital
Des Moines, Iowa, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States
Children's Hospital New Orleans
New Orleans, Louisiana, United States
Ochsner Medical Center Jefferson
New Orleans, Louisiana, United States
Maine Children's Cancer Program
Scarborough, Maine, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, United States
Sinai Hospital of Baltimore
Baltimore, Maryland, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
UMass Memorial Medical Center - University Campus
Worcester, Massachusetts, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, United States
Children's Hospital of Michigan
Detroit, Michigan, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, United States
Bronson Methodist Hospital
Kalamazoo, Michigan, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, United States
Mayo Clinic in Rochester
Rochester, Minnesota, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
University of Missouri Children's Hospital
Columbia, Missouri, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, United States
Cardinal Glennon Children's Medical Center
St Louis, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Morristown Medical Center
Morristown, New Jersey, United States
Jersey Shore Medical Center
Neptune City, New Jersey, United States
Saint Peter's University Hospital
New Brunswick, New Jersey, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, United States
Newark Beth Israel Medical Center
Newark, New Jersey, United States
Albany Medical Center
Albany, New York, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
NYU Langone Hospital - Long Island
Mineola, New York, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
University of Rochester
Rochester, New York, United States
Stony Brook University Medical Center
Stony Brook, New York, United States
State University of New York Upstate Medical University
Syracuse, New York, United States
New York Medical College
Valhalla, New York, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, United States
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, United States
Duke University Medical Center
Durham, North Carolina, United States
East Carolina University
Greenville, North Carolina, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
Children's Hospital Medical Center of Akron
Akron, Ohio, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, United States
Dayton Children's Hospital
Dayton, Ohio, United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Legacy Emanuel Children's Hospital
Portland, Oregon, United States
Oregon Health and Science University
Portland, Oregon, United States
Geisinger Medical Center
Danville, Pennsylvania, United States
Penn State Children's Hospital
Hershey, Pennsylvania, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States
Rhode Island Hospital
Providence, Rhode Island, United States
Prisma Health Richland Hospital
Columbia, South Carolina, United States
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, United States
T C Thompson Children's Hospital
Chattanooga, Tennessee, United States
East Tennessee Childrens Hospital
Knoxville, Tennessee, United States
Saint Jude Children's Research Hospital
Memphis, Tennessee, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States
Texas Tech University Health Sciences Center-Amarillo
Amarillo, Texas, United States
Dell Children's Medical Center of Central Texas
Austin, Texas, United States
Driscoll Children's Hospital
Corpus Christi, Texas, United States
Medical City Dallas Hospital
Dallas, Texas, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, United States
Cook Children's Medical Center
Fort Worth, Texas, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, United States
Covenant Children's Hospital
Lubbock, Texas, United States
UMC Cancer Center / UMC Health System
Lubbock, Texas, United States
Children's Hospital of San Antonio
San Antonio, Texas, United States
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States
Primary Children's Hospital
Salt Lake City, Utah, United States
University of Vermont and State Agricultural College
Burlington, Vermont, United States
University of Virginia Cancer Center
Charlottesville, Virginia, United States
Children's Hospital of The King's Daughters
Norfolk, Virginia, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, United States
Carilion Children's
Roanoke, Virginia, United States
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, United States
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, United States
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States
Alberta Children's Hospital
Calgary, Alberta, Canada
University of Alberta Hospital
Edmonton, Alberta, Canada
CancerCare Manitoba
Winnipeg, Manitoba, Canada
IWK Health Centre
Halifax, Nova Scotia, Canada
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, Canada
Children's Hospital
London, Ontario, Canada
Children's Hospital of Eastern Ontario
Ottawa, Ontario, Canada
Hospital for Sick Children
Toronto, Ontario, Canada
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, Canada
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
Sherbrooke, Quebec, Canada
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
Québec, , Canada
Countries
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Facility Contacts
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Other Identifiers
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NCI-2024-03424
Identifier Type: REGISTRY
Identifier Source: secondary_id
AREN2231
Identifier Type: OTHER
Identifier Source: secondary_id
AREN2231
Identifier Type: OTHER
Identifier Source: secondary_id
AREN2231
Identifier Type: -
Identifier Source: org_study_id
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