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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04322318
Other study ID # AREN1921
Secondary ID NCI-2020-01561AR
Status Recruiting
Phase Phase 2
First received
Last updated
Start date October 19, 2020
Est. completion date July 1, 2027

Study information

Verified date April 2024
Source Children's Oncology Group
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This phase II trial studies how well combination chemotherapy works in treating patients with newly diagnosed stage II-IV diffuse anaplastic Wilms tumors (DAWT) or favorable histology Wilms tumors (FHWT) that have come back (relapsed). Drugs used in chemotherapy regimens such as UH-3 (vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan) and ICE/Cyclo/Topo (ifosfamide, carboplatin, etoposide, cyclophosphamide, and topotecan) work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial may help doctors find out what effects, good and/or bad, regimen UH-3 has on patients with newly diagnosed DAWT and standard risk relapsed FHWT (those treated with only 2 drugs for the initial WT) and regimen ICE/Cyclo/Topo has on patients with high and very high risk relapsed FHWT (those treated with 3 or more drugs for the initial WT).


Description:

PRIMARY OBJECTIVES: I. To evaluate whether the addition of vincristine/irinotecan to cyclophosphamide/ carboplatin/etoposide alternating with vincristine/doxorubicin/cyclophosphamide improves the event-free survival (EFS) of patients with newly diagnosed stage 4 diffuse anaplastic Wilms tumor (DAWT) as compared to historical controls. II. To evaluate whether the addition of vincristine/irinotecan to cyclophosphamide/carboplatin/etoposide alternating with vincristine/doxorubicin/cyclophosphamide improves the EFS of patients with standard-risk relapsed favorable histology Wilms tumor (SRrFHWT) as compared to historical controls. SECONDARY OBJECTIVES: I. To evaluate whether the addition of vincristine/irinotecan to cyclophosphamide/carboplatin/etoposide alternating with vincristine/doxorubicin/cyclophosphamide improves the overall survival (OS) of patients with newly diagnosed stage 4 DAWT as compared to historical controls. II. To evaluate whether the addition of vincristine/irinotecan to cyclophosphamide/carboplatin/etoposide alternating with vincristine/doxorubicin/cyclophosphamide improves the OS of patients with SRrFHWT as compared to historical controls. III. To evaluate whether the addition of vincristine/irinotecan to cyclophosphamide/carboplatin/etoposide alternating with vincristine/doxorubicin/cyclophosphamide improves the EFS and OS of patients with newly diagnosed stage 2 and 3 DAWT as compared to historical controls. IV. To establish EFS and OS for high-risk (HRrFHWT) and very high risk (VHRrFHWT) relapsed favorable histology Wilms tumor treated with ifosfamide/carboplatin/etoposide alternating with cyclophosphamide/ topotecan. EXPLORATORY OBJECTIVES: I. To describe renal toxicity of ifosfamide/carboplatin/etoposide in HRrFHWT and VHRrFHWT patients using conventional and novel biomarkers of renal toxicity (urine NGAL, cystatin C and Kim1) in the context of the chemotherapy regimens used on this study. II. To collect and bank serial blood and urine samples in patients with newly diagnosed DAWT or relapsed FHWT and tumor tissue in patients with relapsed FHWT, for future analysis. III. To assess the impact of p53 gene and protein expression on outcome for patients with newly diagnosed DAWT. IV. To determine EFS/OS in the subsets of patients with newly diagnosed DAWT or relapsed FWHT who undergo gross total resection at all disease sites at diagnosis or after neoadjuvant chemotherapy. V. To describe the rate of regional lymph node sampling at the time of nephrectomy with the use of a pre-operative surgical checklist for patients with newly diagnosed DAWT. VI. To determine the feasibility of intensity modulated radiation therapy (IMRT) with central quality assurance (QA) monitoring to reduce radiation induced toxicity to the heart, thyroid, breast and solitary kidney for children with lung and liver metastases (part of an overarching aim in this study and across frontline favorable histology Wilms tumor studies). OUTLINE: Patients are assigned to 1 of 2 arms. ARM I (REGIMEN UH-3): CYCLES 1, 5, 7, 10, AND 13: Patients receive vincristine intravenously (IV) via minibag per institutional policy on days 1, 8, and 15. Patients also receive doxorubicin IV over 1-15 minutes and cyclophosphamide IV over 30-60 minutes on day 1. Treatment repeats every 21 days during cycles 1, 5, 7, 10, and 13 in the absence of disease progression or unacceptable toxicity. CYCLES 2, 6, 9, 12, AND 14: Patients receive carboplatin IV over 15-60 minutes on day 1. Patients also receive cyclophosphamide IV over 15-30 minutes and etoposide IV over 1-2 hours on days 1-4. Treatment repeats every 21 days during cycles 2, 6, 9, 12, and 14 in the absence of disease progression or unacceptable toxicity. CYCLES 3, 4, 8, AND 11: Patients receive vincristine IV via minibag per institutional policy on days 1 and 8 and irinotecan IV over 90 minutes on days 1-5. Treatment repeats every 21 days during cycles 3, 4, 8, and 11 in the absence of disease progression or unacceptable toxicity. Patients undergo radiation therapy (RT) at week 7 of cycle 3 as clinically indicated. Patients undergo a computed tomography (CT) scan, a positron emission tomography (PET) scan, a chest x-ray, magnetic resonance imaging (MRI), an abdominal ultrasound, and/or a bone scan throughout the trial. Patients may also undergo blood specimen collection and biopsy throughout the trial. ARM II (REGIMEN IFOSFAMIDE, CARBOPLATIN, ETOPOSIDE [ICE]/CYCLOPHOSPHAMIDE [CYCLO]/TOPOTECAN [TOPO]): CYCLES 1, 2, 4, 5, 7, AND 9: Patients receive carboplatin IV over 15-60 minutes on day 1. Patients also receive etoposide IV over 1-2 hours and ifosfamide IV over 2-4 hours on days 1-3. Treatment repeats every 21 days during cycles 1, 2, 4, 5, 7, and 9 in the absence of disease progression or unacceptable toxicity. CYCLES 3, 6, 8, AND 10: Patients receive cyclophosphamide IV over 15-30 minutes and topotecan IV over 30 minutes on days 1-5. Treatment repeats every 21 days during cycles 3, 6, 8, and 10 in the absence of disease progression or unacceptable toxicity. Patients undergo surgery and/or RT during cycles 4, 7, and 10 as clinically indicated. Patients undergo a CT scan, a PET scan, a chest x-ray, MRI, an abdominal ultrasound, and/or a bone scan throughout the trial. Patients may also undergo blood specimen collection and biopsy throughout the trial. After completion of study treatment, patients are followed up every 3 months for years 1-2, every 6 months for years 3-4, and once at year 5.


Recruitment information / eligibility

Status Recruiting
Enrollment 221
Est. completion date July 1, 2027
Est. primary completion date July 1, 2027
Accepts healthy volunteers No
Gender All
Age group N/A to 30 Years
Eligibility Inclusion Criteria: - Patients with newly diagnosed stages 2 - 4 diffuse anaplastic Wilms tumor must be enrolled on AREN03B2 and have received an initial risk assignment showing DAWT (if anaplasia first identified at diagnostic, pre-treatment nephrectomy or biopsy) or a delayed nephrectomy classification showing DAWT (if anaplasia first noted at delayed nephrectomy) prior to enrollment on AREN1921. Prior enrollment on AREN03B2 is not an eligibility requirement for patients with relapsed favorable histology Wilms tumor. - Patients must be =< 30 years old at study enrollment - Patients with the following diagnoses are eligible for this study: - Newly diagnosed stages 2 - 4 diffuse anaplastic Wilms tumor as confirmed by central review - Favorable histology Wilms tumor at first relapse. Relapsed FHWT patients must have previously achieved remission for their initial FHWT diagnosis to be eligible for this study. The relapse risk groups are defined as follows, regardless of radiation therapy: - Standard-Risk relapse: Patients who received two chemotherapy agents for frontline therapy; primarily actinomycin D and vincristine - High-Risk relapse: Patients who received three chemotherapy agents for frontline therapy; primarily vincristine, actinomycin D and doxorubicin or vincristine, actinomycin D and irinotecan - Very High-Risk relapse: Patients who received four or more chemotherapy agents as part of initial therapy; primarily regimen M or its variations - Patients with newly diagnosed DAWT must have had histologic verification of the malignancy. For relapsed FHWT patients, biopsy to prove recurrence is encouraged, but not required - Note: For relapsed FHWT patients, an institutional pathology report confirming favorable histology Wilms tumor (from relapse, if available, or from original diagnosis) must be available for upload prior to initiation of protocol therapy - Patients with newly diagnosed Stages 2 - 4 diffuse anaplastic Wilms tumor must be enrolled on AREN1921 within 2 weeks of the tumor-directed surgery or biopsy procedure that first confirms a diagnosis of DAWT, whether at initial diagnostic procedure or delayed nephrectomy (such surgery/biopsy is day 0). For patients who received prior therapy for presumed favorable histology Wilms tumor, later confirmed to have diffuse anaplastic Wilms tumor at subsequent review of the initial biopsy - Patients with newly diagnosed DAWT who undergo upfront nephrectomy must have at least 1 lymph node sampled prior to study enrollment - Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age - Patients must have a life expectancy of >= 8 weeks - Diffuse Anaplastic Wilms Tumor: Patients with diffuse anaplastic histology must have had no prior systemic therapy, except in the following situations: - Patients with diffuse anaplastic Wilms tumor who received no more than 12 weeks of pre nephrectomy chemotherapy for what was originally presumed to be favorable histology Wilms tumor, subsequently confirmed to be diffuse anaplastic Wilms tumor at delayed nephrectomy - Patients with diffuse anaplastic Wilms tumor who received no more than 6 weeks of chemotherapy following upfront biopsy, initiated within 14 days of biopsy, for presumed favorable histology Wilms tumor based on institutional review, but subsequently corrected to diffuse anaplastic Wilms tumor based on the AREN03B2 initial risk assignment results (if available per current version of AREN03B2) - Treatment consisting of vincristine/doxorubicin/cyclophosphamide initiated on an emergent basis and within allowed timing as described - Note: Patients who received prior therapy for presumed favorable histology Wilms tumor, later identified to have diffuse anaplastic Wilms tumor as per above, must begin study treatment starting at cycle 3 (week 7) of regimen UH 3. Patients who received emergency radiation to preserve organ function are eligible as noted. Patients who received radiation as part of standard of care for presumed newly diagnosed favorable histology Wilms tumor, along with chemotherapy as noted above, prior to identification of diffuse anaplasia, are also eligible - Relapsed Favorable Histology Wilms Tumor: Patients must not have received prior chemotherapy for their relapsed favorable histology Wilms tumor diagnosis. In addition, patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study - Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry onto this study - Radiation therapy (RT): >= 2 weeks (wks) must have elapsed for local palliative RT (small port); >= 6 months must have elapsed if prior craniospinal RT or if >= 50% radiation of pelvis; >= 6 wks must have elapsed if other substantial bone marrow (BM) radiation. Patients with relapsed favorable histology Wilms tumor who received emergency radiation to preserve organ function are eligible and do not need to washout with the above criteria - Patients may not be receiving any other investigational agents (within 4 weeks prior to study enrollment) - Peripheral absolute neutrophil count (ANC) >= 750/uL (performed within 7 days prior to enrollment) - Platelet count >= 75,000/uL (transfusion independent) (performed within 7 days prior to enrollment) - Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (performed within 7 days prior to enrollment) - Patients with high-risk or very high-risk relapsed FHWT who will be treated with regimen ICE/Cyclo/Topo, must have renal function assessed by creatinine clearance or radioisotope glomerular filtration rate (GFR) and meet the following requirement: - Creatinine clearance or radioisotope GFR >= 60 mL/min/1.73 m^2 (performed within 7 days prior to enrollment) - Patients diagnosed with stage 2-4 DAWT or standard risk relapsed FHWT, who will be treated with regimen UH 3, may either obtain a creatinine clearance, radioisotope GFR (meeting the above criteria of GFR >= 60 mL/min/1.73 m^2), or an adequate serum creatinine as per the following table: - Age: Maximum Serum Creatinine (mg/dL) - 1 month to < 6 months: 0.4 (male and female) - 6 months to < 1 year: 0.5 (male and female) - 1 to < 2 years: 0.6 (male and female) - 2 to < 6 years: 0.8 (male and female) - 6 to < 10 years: 1 (male and female) - 10 to < 13 years: 1.2 (male and female) - 13 to < 16 years: 1.5 (male), 1.4 (female) - >= 16 years: 1.7 (male), 1.4 (female) - Total bilirubin =< 1.5 x upper limit of normal (ULN) for age or direct bilirubin =< ULN for patients whose total bilirubin > 1.5 x ULN (performed within 7 days prior to enrollment) - Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x upper limit of normal (ULN) for age or =< 5 x ULN for patients with liver metastases (performed within 7 days prior to enrollment) - Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by radionuclide angiogram (obtained within 21 days prior to enrollment and start of protocol therapy) Exclusion Criteria: - Patients with a history of bilateral Wilms tumor (synchronous or metachronous) - Patients with any uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, or symptomatic congestive heart failure (defined as grade 2 or higher heart failure per Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) - Relapsed FHWT patients who did not receive frontline chemotherapy (e.g., very low risk FHWT initially observed without chemotherapy) or received only one chemotherapy agent for frontline therapy - For patients with high-risk or very high-risk relapsed FHWT: - Patients with renal tubular acidosis (RTA) as evidenced by serum bicarbonate < 16 mmol/L and serum phosphate =< 2 mg/dL (or < 0.8 mmol/L) without supplementation - For stages 2-4 DAWT and standard-risk relapsed FHWT patients: - Chronic inflammatory bowel disease and/or bowel obstruction - Concomitant use of St. John's wort, which cannot be stopped prior to the start of trial treatment - 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

Study Design


Intervention

Procedure:
Biopsy
Undergo a biopsy
Biospecimen Collection
Undergo blood sample collection
Bone Scan
Undergo a bone scan
Drug:
Carboplatin
Given IV
Procedure:
Computed Tomography
Undergo a CT scan
Drug:
Cyclophosphamide
Given IV
Doxorubicin
Given IV
Etoposide
Given IV
Ifosfamide
Given IV
Irinotecan
Given IV
Procedure:
Magnetic Resonance Imaging
Undergo MRI
Positron Emission Tomography
Undergo a PET scan
Radiation:
Radiation Therapy
Undergo RT
Procedure:
Surgical Procedure
Undergo surgery
Drug:
Topotecan
Given IV
Procedure:
Transabdominal Ultrasound
Undergo abdominal ultrasound
Drug:
Vincristine
Given IV
Procedure:
X-Ray Imaging
Undergo a chest x-ray

Locations

Country Name City State
Australia Monash Medical Center-Clayton Campus Clayton Victoria
Australia John Hunter Children's Hospital Hunter Regional Mail Centre New South Wales
Australia Women's and Children's Hospital-Adelaide North Adelaide South Australia
Australia Royal Children's Hospital Parkville Victoria
Australia Perth Children's Hospital Perth Western Australia
Australia Sydney Children's Hospital Randwick New South Wales
Australia Queensland Children's Hospital South Brisbane Queensland
Australia The Children's Hospital at Westmead Westmead New South Wales
Canada Alberta Children's Hospital Calgary Alberta
Canada University of Alberta Hospital Edmonton Alberta
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 Centre Hospitalier Universitaire Sainte-Justine Montreal Quebec
Canada The Montreal Children's Hospital of the MUHC Montreal Quebec
Canada Children's Hospital of Eastern Ontario Ottawa Ontario
Canada CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL) Quebec
Canada Janeway Child Health Centre Saint John's Newfoundland and Labrador
Canada Centre Hospitalier Universitaire de Sherbrooke-Fleurimont Sherbrooke Quebec
Canada Hospital for Sick Children Toronto Ontario
Canada British Columbia Children's Hospital Vancouver British Columbia
Canada CancerCare Manitoba Winnipeg Manitoba
New Zealand Christchurch Hospital Christchurch
New Zealand Starship Children's Hospital Grafton Auckland
Puerto Rico HIMA San Pablo Oncologic Hospital Caguas
Puerto Rico University Pediatric Hospital San Juan
Saudi Arabia King Faisal Specialist Hospital and Research Centre Riyadh
United States Children's Hospital Medical Center of Akron Akron Ohio
United States Albany Medical Center Albany New York
United States Lehigh Valley Hospital-Cedar Crest Allentown Pennsylvania
United States Texas Tech University Health Sciences Center-Amarillo Amarillo Texas
United States Providence Alaska Medical Center Anchorage Alaska
United States C S Mott Children's Hospital Ann Arbor Michigan
United States Mission Hospital Asheville North Carolina
United States Children's Healthcare of Atlanta - Egleston Atlanta Georgia
United States Children's Hospital Colorado Aurora Colorado
United States Dell Children's Medical Center of Central Texas Austin Texas
United States Johns Hopkins University/Sidney Kimmel Cancer Center Baltimore Maryland
United States Sinai Hospital of Baltimore Baltimore Maryland
United States Eastern Maine Medical Center Bangor Maine
United States Children's Hospital of Alabama Birmingham Alabama
United States Saint Luke's Cancer Institute - Boise Boise Idaho
United States Dana-Farber Cancer Institute Boston Massachusetts
United States Tufts Children's Hospital Boston Massachusetts
United States Montefiore Medical Center - Moses Campus Bronx New York
United States Roswell Park Cancer Institute Buffalo New York
United States Medical University of South Carolina Charleston South Carolina
United States West Virginia University Charleston Division Charleston West Virginia
United States Carolinas Medical Center/Levine Cancer Institute Charlotte North Carolina
United States Novant Health Presbyterian Medical Center Charlotte North Carolina
United States University of Virginia Cancer Center Charlottesville Virginia
United States T C Thompson Children's Hospital Chattanooga Tennessee
United States Lurie Children's Hospital-Chicago Chicago Illinois
United States University of Chicago Comprehensive Cancer Center Chicago Illinois
United States University of Illinois Chicago Illinois
United States Cincinnati Children's Hospital Medical Center Cincinnati Ohio
United States Cleveland Clinic Foundation Cleveland Ohio
United States Rainbow Babies and Childrens Hospital Cleveland Ohio
United States Columbia Regional Columbia Missouri
United States Prisma Health Richland Hospital Columbia South Carolina
United States Nationwide Children's Hospital Columbus Ohio
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 Geisinger Medical Center Danville Pennsylvania
United States Dayton Children's Hospital Dayton Ohio
United States Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center Denver Colorado
United States Blank Children's Hospital Des Moines Iowa
United States Children's Hospital of Michigan Detroit Michigan
United States Kaiser Permanente Downey Medical Center Downey California
United States Duke University Medical Center Durham North Carolina
United States Michigan State University Clinical Center East Lansing Michigan
United States El Paso Children's Hospital El Paso Texas
United States Inova Fairfax Hospital Falls Church Virginia
United States Sanford Broadway Medical Center Fargo North Dakota
United States Golisano Children's Hospital of Southwest Florida Fort Myers Florida
United States Cook Children's Medical Center Fort Worth Texas
United States University of Florida Health Science Center - Gainesville Gainesville Florida
United States Helen DeVos Children's Hospital at Spectrum Health Grand Rapids Michigan
United States BI-LO Charities Children's Cancer Center Greenville South Carolina
United States East Carolina University Greenville North Carolina
United States Hackensack University Medical Center Hackensack New Jersey
United States Connecticut Children's Medical Center Hartford Connecticut
United States Penn State Children's Hospital Hershey Pennsylvania
United States Memorial Regional Hospital/Joe DiMaggio Children's Hospital Hollywood Florida
United States Kapiolani Medical Center for Women and Children Honolulu Hawaii
United States Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center Houston Texas
United States M D Anderson Cancer Center Houston Texas
United States Edwards Comprehensive Cancer Center Huntington West Virginia
United States Riley Hospital for Children Indianapolis Indiana
United States University of Iowa/Holden Comprehensive Cancer Center Iowa City Iowa
United States University of Mississippi Medical Center Jackson Mississippi
United States Nemours Children's Clinic-Jacksonville Jacksonville Florida
United States Bronson Methodist Hospital Kalamazoo Michigan
United States Children's Mercy Hospitals and Clinics Kansas City Missouri
United States East Tennessee Childrens Hospital Knoxville Tennessee
United States Alliance for Childhood Diseases/Cure 4 the Kids Foundation Las Vegas Nevada
United States Summerlin Hospital Medical Center Las Vegas Nevada
United States Sunrise Hospital and Medical Center Las Vegas Nevada
United States University Medical Center of Southern Nevada Las Vegas Nevada
United States University of Kentucky/Markey Cancer Center Lexington Kentucky
United States Arkansas Children's Hospital Little Rock Arkansas
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 Cedars Sinai Medical Center Los Angeles California
United States Children's Hospital Los Angeles Los Angeles California
United States Mattel Children's Hospital UCLA Los Angeles California
United States Norton Children's Hospital Louisville Kentucky
United States Covenant Children's Hospital Lubbock Texas
United States UMC Cancer Center / UMC Health System Lubbock Texas
United States Medical Center of Central Georgia Macon Georgia
United States Valley Children's Hospital Madera California
United States University of Wisconsin Carbone Cancer Center Madison Wisconsin
United States Marshfield Medical Center-Marshfield Marshfield Wisconsin
United States Loyola University Medical Center Maywood Illinois
United States Saint Jude Children's Research Hospital Memphis Tennessee
United States Banner Children's at Desert Mesa Arizona
United States Nicklaus Children's Hospital Miami Florida
United States University of Miami Miller School of Medicine-Sylvester Cancer Center Miami Florida
United States Children's Hospital of Wisconsin Milwaukee Wisconsin
United States Children's Hospitals and Clinics of Minnesota - Minneapolis Minneapolis Minnesota
United States University of Minnesota/Masonic Cancer Center Minneapolis Minnesota
United States USA Health Strada Patient Care Center Mobile Alabama
United States Morristown Medical Center Morristown New Jersey
United States The Children's Hospital at TriStar Centennial Nashville Tennessee
United States Vanderbilt University/Ingram Cancer Center Nashville Tennessee
United States Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital New Brunswick New Jersey
United States Yale University New Haven Connecticut
United States The Steven and Alexandra Cohen Children's Medical Center of New York New Hyde Park New York
United States Children's Hospital New Orleans New Orleans Louisiana
United States Ochsner Medical Center Jefferson New Orleans Louisiana
United States Memorial Sloan Kettering Cancer Center New York New York
United States NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center New York New York
United States NYP/Weill Cornell Medical Center New York New York
United States Children's Hospital of The King's Daughters Norfolk Virginia
United States Advocate Children's Hospital-Oak Lawn Oak Lawn Illinois
United States Kaiser Permanente-Oakland Oakland California
United States UCSF Benioff Children's Hospital Oakland Oakland California
United States University of Oklahoma Health Sciences Center Oklahoma City Oklahoma
United States Children's Hospital and Medical Center of Omaha Omaha Nebraska
United States University of Nebraska Medical Center Omaha Nebraska
United States Children's Hospital of Orange County Orange California
United States Arnold Palmer Hospital for Children Orlando Florida
United States Nemours Children's Hospital Orlando Florida
United States Lucile Packard Children's Hospital Stanford University Palo Alto California
United States Advocate Children's Hospital-Park Ridge Park Ridge Illinois
United States Saint Joseph's Regional Medical Center Paterson New Jersey
United States Sacred Heart Hospital Pensacola Florida
United States Saint Jude Midwest Affiliate Peoria Illinois
United States Children's Hospital of Philadelphia Philadelphia Pennsylvania
United States Saint Christopher's Hospital for Children Philadelphia Pennsylvania
United States Children's Hospital of Pittsburgh of UPMC Pittsburgh Pennsylvania
United States Legacy Emanuel Children's Hospital Portland Oregon
United States Oregon Health and Science University Portland Oregon
United States Rhode Island Hospital Providence Rhode Island
United States Renown Regional Medical Center Reno Nevada
United States Virginia Commonwealth University/Massey Cancer Center Richmond Virginia
United States Carilion Children's Roanoke Virginia
United States Mayo Clinic in Rochester Rochester Minnesota
United States Beaumont Children's Hospital-Royal Oak Royal Oak Michigan
United States University of California Davis Comprehensive Cancer Center Sacramento California
United States Cardinal Glennon Children's Medical Center Saint Louis Missouri
United States Mercy Hospital Saint Louis Saint Louis Missouri
United States Washington University School of Medicine Saint Louis Missouri
United States Johns Hopkins All Children's Hospital Saint Petersburg Florida
United States Primary Children's Hospital Salt Lake City Utah
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 Rady Children's Hospital - San Diego San Diego California
United States UCSF Medical Center-Mission Bay San Francisco California
United States Memorial Health University Medical Center Savannah Georgia
United States Maine Children's Cancer Program Scarborough Maine
United States Seattle Children's Hospital Seattle Washington
United States Sanford USD Medical Center - Sioux Falls Sioux Falls South Dakota
United States Providence Sacred Heart Medical Center and Children's Hospital Spokane Washington
United States Southern Illinois University School of Medicine Springfield Illinois
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 Madigan Army Medical Center Tacoma Washington
United States Mary Bridge Children's Hospital and Health Center Tacoma Washington
United States Saint Joseph's Hospital/Children's Hospital-Tampa Tampa Florida
United States Tampa General Hospital Tampa Florida
United States ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital Toledo Ohio
United States Banner University Medical Center - Tucson Tucson Arizona
United States New York Medical College Valhalla New York
United States Children's National Medical Center Washington District of Columbia
United States MedStar Georgetown University Hospital Washington District of Columbia
United States Saint Mary's Hospital West Palm Beach Florida
United States Alfred I duPont Hospital for Children Wilmington Delaware
United States Wake Forest University Health Sciences Winston-Salem North Carolina
United States UMass Memorial Medical Center - University Campus Worcester Massachusetts

Sponsors (2)

Lead Sponsor Collaborator
Children's Oncology Group National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada,  New Zealand,  Puerto Rico,  Saudi Arabia, 

Outcome

Type Measure Description Time frame Safety issue
Other Incidence of grade 3-5 renal toxicity Incidence of grade 3-5 renal toxicity during protocol therapy will be monitored for Stratum 4 as part of a prospective safety monitoring plan. At the time of final study analysis, renal toxicity will be described by factors including age, relapse risk group, and timing and association (descriptive) with the exploratory renal toxicity biomarkers. Up to 30 weeks on average for Stratum 4 only
Other Collection of blood and urine samples For all Strata 1-4, serial blood and urine samples will be collected (during protocol therapy, at the end of protocol therapy, and at first relapse) and banked for future analysis such as evaluation of minimal residual disease by assessing levels of circulating tumor-derived deoxyribonucleic acid. Up to 42 weeks on average for Strata 1-3 and up to 30 weeks on average for Stratum 4
Other p53 biomarker analysis For patients with diffuse anaplastic Wilms tumors (DAWT) (Strata 1 and 2), p53 from diagnostic tissue will be assessed, and rates of p53 mutations described overall and within each stratum. Degree of anaplasia as a predictor of p53 mutation status will be analyzed in logistic regression models, and association of p53 status with EFS and OS will be analyzed in Cox regression models, stratified by disease stage. Possible interactions between p53 mutation status and degree of anaplasia in outcome models will be explored. Based on tissue collected at diagnosis (Strata 1 and 2 only), with outcomes collected up to 5 years after study entry
Other EFS for patients with gross total disease resection EFS will be described for newly diagnosed disease stage 2-4 DAWT patients (Strata 1 and 2) and relapsed favorable histology Wilms tumors (FHWT) patients (Strata 3 and 4) who have gross total disease resection prior to enrollment or at the time of delayed nephrectomy following adjuvant chemotherapy. Kaplan-Meier curves will be reported by strata with 95% confidence bands. Potential prognostic factors for these patients will be explored in Cox regression models. From study entry to the earliest of relapse or disease progression, second malignant neoplasm, or death from any cause, assessed up to 5 years after study enrollment
Other OS for patients with gross total disease resection OS will be described for newly diagnosed disease stage 2-4 DAWT patients (Strata 1 and 2) and relapsed FHWT patients (Strata 3 and 4) who have gross total disease resection prior to enrollment or at the time of delayed nephrectomy following adjuvant chemotherapy. Kaplan-Meier curves will be reported by strata with 95% confidence bands. Potential prognostic factors for these patients will be explored in Cox regression models. From study entry to death due to any cause, assessed up to 5 years after study entry
Other Association of the number of nodes examined with EFS and OS The number of lymph nodes examined at the time of primary nephrectomy and number of positive nodes will be collected for all DAWT patients who enroll to Strata 1 or 2. The association of the number of nodes examined with EFS and OS will be explored in Cox regression models stratified by disease stage. For each of these analyses, association will be expressed either as a single hazard ratio if the effect is found to be linear, or as continuous functions on the hazard ratio scale if the effect is found to be non-linear. Similar models will be fit to examine the association between ratio of positive nodes to nodes examined and outcomes. Confidence intervals or bands will be reported for all quantities. Nodal information from upfront or delayed nephrectomy, with outcomes collected for up to 5 years after study entry
Primary Event-free survival (EFS) For Strata 1-3, the primary analysis of EFS will consist of a one-sample, one-sided log rank test versus a historical control cohort (or representative distribution) with stratum-specific type I error levels. For Stratum 4, the primary analysis of EFS is descriptive, but with a desired level of precision to estimate 4-year EFS at the time of the final analysis (2 years after the last patient enrolls). From study entry to the earliest of relapse or disease progression, second malignant neoplasm, or death from any cause, assessed up to 5 years after study enrollment
Secondary Overall survival (OS) For each stratum, OS will be estimated at the same time as the conclusive (interim or final) analysis and reported descriptively with 95% pointwise confidence bands. From study entry to death due to any cause, assessed up to 5 years after study enrollment
See also
  Status Clinical Trial Phase
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Active, not recruiting NCT00352534 - Vincristine, Dactinomycin, and Doxorubicin With or Without Radiation Therapy or Observation Only in Treating Younger Patients Who Are Undergoing Surgery for Newly Diagnosed Stage I, Stage II, or Stage III Wilms' Tumor Phase 3
Not yet recruiting NCT06401330 - A Study Using Risk Factors to Determine Treatment for Children With Favorable Histology Wilms Tumors (FHWT) Phase 3
Active, not recruiting NCT00945009 - Combination Chemotherapy and Surgery in Treating Young Patients With Wilms Tumor Phase 3
Active, not recruiting NCT00379340 - Combination Chemotherapy With or Without Radiation Therapy in Treating Young Patients With Newly Diagnosed Stage III or Stage IV Wilms' Tumor Phase 3