RECRUITING Phase 3 ClinicalTrials.gov

A Study Using Risk Factors to Determine Treatment for Children With Favorable Histology Wilms Tumors (FHWT)

Sponsor: Children's Oncology Group • ClinicalTrials.gov ID: NCT06401330

Registry updated: 2026-08-25

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Description

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.

Interventions

Bone Scan (Procedure)
Undergo bone scan for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Carboplatin (Drug)
Given IV
Computed Tomography (Procedure)
Undergo CT
Cyclophosphamide (Drug)
Given IV
Dactinomycin (Biological)
Given IV
Doxorubicin (Drug)
Given IV
Etoposide (Drug)
Given IV
Irinotecan (Drug)
Given IV
Magnetic Resonance Imaging (Procedure)
Undergo MRI
Nephrectomy (Procedure)
Undergo nephrectomy
Patient Observation (Other)
Undergo observation after nephrectomy
Positron Emission Tomography (Procedure)
Undergo PET for patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy
Ultrasound Imaging (Procedure)
Undergo ultrasound
Vincristine (Drug)
Given IV
X-Ray Imaging (Procedure)
Undergo X-ray

Eligibility criteria

Inclusion Criteria: * 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-REN. * 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. * 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: * 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. * 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.

Conditions

Stage I Mixed Cell Type Kidney Wilms Tumor Stage II Mixed Cell Type Kidney Wilms Tumor Stage III Mixed Cell Type Kidney Wilms Tumor Stage IV Mixed Cell Type Kidney Wilms Tumor

Locations

Children's Hospital of Alabama — Birmingham, Alabama, United States
USA Health Strada Patient Care Center — Mobile, 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
Banner University Medical Center - Tucson — Tucson, Arizona, United States
Arkansas Children's Hospital — Little Rock, Arkansas, United States
Kaiser Permanente Downey Medical Center — Downey, California, United States
City of Hope Comprehensive Cancer Center — Duarte, California, United States
Loma Linda University Medical Center — Loma Linda, California, United States
Miller Children's and Women's Hospital Long Beach — Long Beach, California, United States
Children's Hospital Los Angeles — Los Angeles, 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
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center — Denver, 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
Johns Hopkins All Children's Hospital — St. Petersburg, 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
OSF Children's Hospital of Illinois — Peoria, Illinois, United States
Southern Illinois University School of Medicine — Springfield, 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
Norton Children's Hospital — Louisville, 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
Baystate Medical Center — Springfield, 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
Presbyterian Hospital — Albuquerque, New Mexico, 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
The Steven and Alexandra Cohen Children's Medical Center of New York — New Hyde Park, 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
NYP/Weill Cornell Medical 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
Saint Francis Children's Hospital — Tulsa, 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
Inova Fairfax Hospital — Falls Church, 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
Seattle Children's Hospital — Seattle, Washington, 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
University of Wisconsin Carbone Cancer Center - University Hospital — Madison, Wisconsin, United States
Children's Hospital of Wisconsin — Milwaukee, Wisconsin, United States
Queensland Children's Hospital — South Brisbane, Queensland, Australia
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
Starship Children's Hospital — Grafton, Auckland, New Zealand
Christchurch Hospital — Christchurch, New Zealand

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Data sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

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