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NCT04322318 · CITED IN SOURCE DOCUMENTS

A Study of Combination Chemotherapy for Patients With Newly Diagnosed DAWT and Relapsed FHWT

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

Phase
PHASE2
Status at capture
RECRUITING
Registry last update
2026-08-25

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).

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What did the study report?

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

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility Criteria
Inclusion Criteria: * Patients with newly diagnosed stages 2 - 4 diffuse anaplastic Wilms tumor must be enrolled on APEC14B1, consented to Part A - Eligibility Screening, and have received an initial stratum assignment showing DAWT (if anaplasia first identified at diagnostic, pre-treatment nephrectomy or biopsy) or a final stratum assignment showing DAWT (if anaplasia first noted at delayed nephrectomy) prior to enrollment on AREN1921. Prior enrollment on APEC14B1 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 initial stratum assignment on APEC14B1-REN * 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
healthy Volunteers
false
maximum Age
30 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
arm Groups
  1. description
    See outline in detailed description section.
    intervention Names
    1. Procedure: Biopsy Procedure
    2. Procedure: Biospecimen Collection
    3. Procedure: Bone Scan
    4. Drug: Carboplatin
    5. Procedure: Computed Tomography
    6. Drug: Cyclophosphamide
    7. Drug: Doxorubicin
    8. Drug: Etoposide
    9. Drug: Irinotecan
    10. Procedure: Magnetic Resonance Imaging
    11. Procedure: Positron Emission Tomography
    12. Radiation: Radiation Therapy
    label
    Arm I (Regimen UH-3)
    type
    EXPERIMENTAL
  2. description
    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.
    intervention Names
    1. Procedure: Biopsy Procedure
    2. Procedure: Biospecimen Collection
    3. Procedure: Bone Scan
    4. Drug: Carboplatin
    5. Procedure: Computed Tomography
    6. Drug: Cyclophosphamide
    7. Drug: Etoposide
    8. Drug: Ifosfamide
    9. Procedure: Magnetic Resonance Imaging
    10. Procedure: Positron Emission Tomography
    11. Radiation: Radiation Therapy
    12. Procedure: Surgical Procedure
    label
    Arm II (Regimen ICE/Cyclo/Topo)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Arm I (Regimen UH-3)
    2. Arm II (Regimen ICE/Cyclo/Topo)
    description
    Undergo a biopsy
    name
    Biopsy Procedure
    other Names
    1. Biopsy
    2. BIOPSY_TYPE
    3. Bx
    type
    PROCEDURE
  2. arm Group Labels
    1. Arm I (Regimen UH-3)
    2. Arm II (Regimen ICE/Cyclo/Topo)
    description
    Undergo blood sample collection
    name
    Biospecimen Collection
    other Names
    1. Biological Sample Collection
    2. Biospecimen Collected
    3. Specimen Collection
    type
    PROCEDURE
  3. arm Group Labels
    1. Arm I (Regimen UH-3)
    2. Arm II (Regimen ICE/Cyclo/Topo)
    description
    Undergo a bone scan
    name
    Bone Scan
    other Names
    1. Bone Scintigraphy
    type
    PROCEDURE
  4. arm Group Labels
    1. Arm I (Regimen UH-3)
    2. Arm II (Regimen ICE/Cyclo/Topo)
    description
    Given IV
    name
    Carboplatin
    other Names
    1. Blastocarb
    2. Carboplat
    3. Carboplatin Hexal
    4. Carboplatino
    5. Carboplatinum
    6. Carbosin
    7. Carbosol
    8. Carbotec
    9. CBDCA
    10. Displata
    11. Ercar
    12. JM-8
    type
    DRUG
  5. arm Group Labels
    1. Arm I (Regimen UH-3)
    2. Arm II (Regimen ICE/Cyclo/Topo)
    description
    Undergo a CT scan
    name
    Computed Tomography
    other Names
    1. CAT
    2. CAT Scan
    3. Computed Axial Tomography
    4. Computerized Axial Tomography
    5. Computerized axial tomography (procedure)
    6. Computerized Tomography
    7. Computerized Tomography (CT) scan
    8. CT
    9. CT Scan
    10. tomography
    type
    PROCEDURE
  6. arm Group Labels
    1. Arm I (Regimen UH-3)
    2. Arm II (Regimen ICE/Cyclo/Topo)
    description
    Given IV
    name
    Cyclophosphamide
    other Names
    1. (-)-Cyclophosphamide
    2. 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
    3. Asta B 518
    4. B 518
    5. B-518
    6. B518
    7. Carloxan
    8. Ciclofosfamida
    9. Ciclofosfamide
    10. Cicloxal
    11. Clafen
    12. Claphene
    type
    DRUG
  7. arm Group Labels
    1. Arm I (Regimen UH-3)
    description
    Given IV
    name
    Doxorubicin
    other Names
    1. Adriablastin
    2. Hydroxydaunomycin
    3. Hydroxyl Daunorubicin
    4. Hydroxyldaunorubicin
    type
    DRUG
  8. arm Group Labels
    1. Arm I (Regimen UH-3)
    2. Arm II (Regimen ICE/Cyclo/Topo)
    description
    Given IV
    name
    Etoposide
    other Names
    1. Demethyl Epipodophyllotoxin Ethylidine Glucoside
    2. EPEG
    3. Lastet
    4. Toposar
    5. Vepesid
    6. VP 16
    7. VP 16-213
    8. VP 16213
    9. VP-16
    10. VP-16-213
    11. VP-16213
    12. VP16
    type
    DRUG
  9. arm Group Labels
    1. Arm II (Regimen ICE/Cyclo/Topo)
    description
    Given IV
    name
    Ifosfamide
    other Names
    1. Asta Z 4942
    2. Asta Z-4942
    3. Cyfos
    4. Holoxan
    5. Holoxane
    6. Ifex
    7. IFO
    8. IFO-Cell
    9. Ifolem
    10. Ifomida
    11. Ifomide
    12. Ifosfamidum
    type
    DRUG
  10. arm Group Labels
    1. Arm I (Regimen UH-3)
    description
    Given IV
    name
    Irinotecan
    type
    DRUG
  11. arm Group Labels
    1. Arm I (Regimen UH-3)
    2. Arm II (Regimen ICE/Cyclo/Topo)
    description
    Undergo MRI
    name
    Magnetic Resonance Imaging
    other Names
    1. Magnetic Resonance
    2. Magnetic Resonance Imaging (MRI)
    3. Magnetic resonance imaging (procedure)
    4. Magnetic Resonance Imaging Scan
    5. Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
    6. MR
    7. MR Imaging
    8. MRI
    9. MRI Scan
    10. MRIs
    11. NMR Imaging
    12. NMRI
    type
    PROCEDURE
  12. arm Group Labels
    1. Arm I (Regimen UH-3)
    2. Arm II (Regimen ICE/Cyclo/Topo)
    description
    Undergo a PET scan
    name
    Positron Emission Tomography
    other Names
    1. Medical Imaging, Positron Emission Tomography
    2. PET
    3. PET Scan
    4. Positron emission tomography (procedure)
    5. Positron Emission Tomography Scan
    6. Positron-Emission Tomography
    7. PT
    type
    PROCEDURE
Study design
allocation
NON_RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
256
type
ESTIMATED
Registered outcome plans (not posted results)
other Outcomes
  1. description
    Percentage of patients experiencing grade 3 or higher renal adverse events. Will be evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
    measure
    Percentage of patients experiencing grade 3+ renal adverse events
    time Frame
    Up to 30 weeks on average for Stratum 4 only
  2. description
    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 (ctDNA).
    measure
    Collection of blood and urine samples
    time Frame
    Up to 42 weeks on average for Strata 1-3 and up to 30 weeks on average for Stratum 4
  3. description
    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.
    measure
    p53 biomarker analysis
    time Frame
    Based on tissue collected at diagnosis (Strata 1 and 2 only), with outcomes collected up to 5 years after study entry
  4. description
    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.
    measure
    EFS for patients with gross total disease resection
    time Frame
    Up to 5 years after study entry
  5. description
    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.
    measure
    OS for patients with gross total disease resection
    time Frame
    Up to 5 years after study entry
  6. description
    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.
    measure
    Association of the number of nodes examined with EFS and OS
    time Frame
    Nodal information from upfront or delayed nephrectomy, with outcomes collected for up to 5 years after study entry
  7. description
    Will be reported descriptively for cohorts receiving radiation.
    measure
    Rates of usage of intensity-modulated radiation therapy
    time Frame
    Up to 7 or 30 weeks
  8. description
    Presence/absence of ctDNA at study entry (diagnosis for DAWT Strata 1 and 2, and first relapse for relapsed FHWT Strata 3 and 4) as well as ctDNA levels as a continuous variable will be associated with subsequent EFS using Kaplan-Meier methodology, log-rank tests, and Cox proportional hazards modeling. ctDNA over time (diagnosis, on treatment, and off treatment) will be associated with clinical outcomes using longitudinal modeling. Where sufficient EFS events exist, ctDNA will be evaluated alongside or in combination with other known risk factors to establish risk groups. Genomic features such as TP53 and 1q gain identified in ctDNA will be reported descriptively and correlated with tumor-based marker findings.
    measure
    Detection and quantification of ctDNA
    time Frame
    Up to 42 weeks on average for Strata 1-3 and up to 30 weeks on average for Stratum 4
primary Outcomes
  1. description
    Kaplan-Meier method will be used to estimate EFS, defined as the time from study entry until relapse or disease progression, secondary malignancy, or death.
    measure
    Event-free survival (EFS) for stratum 1-3
    time Frame
    From study entry to the earliest of relapse or disease progression, second malignant neoplasm, or death from any cause, assessed up to 5 years from study entry
  2. description
    Kaplan-Meier method will be used to estimate 4-year EFS, defined as the time from study entry until relapse or disease progression, secondary malignancy, or death.
    measure
    EFS for stratum 4
    time Frame
    From study entry to the earliest of relapse or disease progression, second malignant neoplasm, or death from any cause, assessed up to 5 years from study entry
secondary Outcomes
  1. description
    The Kaplan-Meier method will be used to estimate OS, defined as the time from study entry until death.
    measure
    Overall survival (OS) for stratum 1-4
    time Frame
    From study entry to death due to any cause, assessed up to 5 years from study entry
Full study description
brief 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).
detailed 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). VII. To validate that circulating tumor-derived deoxyribonucleic acid (ctDNA) can identify high-risk genomic features, define prognostic risk groups, and identify patterns of tumor evolution associated with the development of treatment resistance. 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.
Source references
Source notices and limitations
    Discovery and provenance
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      occurrences
      1. context exact
        nical trial that is currently being conducted:</p> </section> <div class="pdq-content-list"><ul id="_2022"><li><strong><a href="/clinicaltrials/NCT04322318">AREN1921 (NCT04322318)</a></strong> (A Study of Combination Chemotherapy for Patients With Newly Diagnosed Diffuse Anaplastic Wilms Tumors and Relapsed Favora
        end
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        exact text
        NCT04322318
        start
        259393
      2. context exact
        rently being conducted:</p> </section> <div class="pdq-content-list"><ul id="_2022"><li><strong><a href="/clinicaltrials/NCT04322318">AREN1921 (NCT04322318)</a></strong> (A Study of Combination Chemotherapy for Patients With Newly Diagnosed Diffuse Anaplastic Wilms Tumors and Relapsed Favorable-Histology Wilms Tum
        end
        259427
        exact text
        NCT04322318
        start
        259416
      3. context exact
        institutional clinical trial that is currently being conducted:</p> <div class="pdq-content-list"><ul id="_1826"><li><strong><a href="/clinicaltrials/NCT04322318">AREN1921 (NCT04322318)</a></strong> (A Study of Combination Chemotherapy for Patients With Newly Diagnosed Diffuse Anaplastic Wilms Tumor and Relapsed Favorab
        end
        298087
        exact text
        NCT04322318
        start
        298076
      4. context exact
        trial that is currently being conducted:</p> <div class="pdq-content-list"><ul id="_1826"><li><strong><a href="/clinicaltrials/NCT04322318">AREN1921 (NCT04322318)</a></strong> (A Study of Combination Chemotherapy for Patients With Newly Diagnosed Diffuse Anaplastic Wilms Tumor and Relapsed Favorable-Histology [FH] Wilms
        end
        298110
        exact text
        NCT04322318
        start
        298099
      offset unit
      unicode_code_points
      source file
      /tmp/cancer-full-research/nci/raw/21c44e98d92c4ee887.html
      source file sha256
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      source json pointer
      Source null
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source retrieved at
      2026-09-09T23:21:51.520868+00:00
      source string basis
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      source string sha256
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      source title
      Wilms Tumor and Other Childhood Kidney Tumors Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: April 15, 2025
        datetime
        2025-04-15T12:00:00Z
        display
        April 15, 2025

    Preserved source evidence · Not medical advice