ClinicalTrials.gg
Sign In
RecruitingNCT04322318Updated Aug 25, 2026

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

A Phase 2 interventional study of Biopsy Procedure and Biospecimen Collection in Anaplastic Kidney Wilms Tumor, Recurrent Kidney Wilms Tumor and Stage II Kidney Wilms Tumor, sponsored by Children's Oncology Group. Recruiting at 205 sites in 6 countries. Open to participants aged Up to 30 Years. Per ClinicalTrials.gov, last updated 2026-08-25.

Sponsored by Children's Oncology Group · Phase 2, Interventional, and Treatment

From the registry’s dates

  • Started Oct 2020; still recruiting 6 years later.
Phase
Phase 2
Study type
Interventional
Enrollment
256
Allocation
Non-randomized
Ages
Up to 30 Years
Sex
All
01

Where this study stands

Counted across the records on this site · 2026-11-12

Among 12 studies testing doxorubicin in Wilms Tumor — 3 open to participants now, 3 under way, 1 of them phase 3. Doxorubicin · Wilms Tumor.

Planned enrollment
6th of 10
256 · median 274
Started
2020
the only one that year
Phase 2
4 of 12
1 open now
Registered
11th of 12
by date
Lead sponsor
8 of 12
Children's Oncology Group

Among the 12 studies testing doxorubicin in Wilms Tumor, this one is the 6th largest by planned enrollment of the 10 interventional ones, is the only one that started in 2020, is one of 4 in phase 2, and was the 11th registered.

By phase

12 studies; the count open now beside each. This study's row is marked.

Phase 36 · 1 open
Phase 2this study4 · 1 open
Phase 11 · 0 open
Phase 41 · 1 open

By the year they started

First in 1990; this study’s year is marked. 1 started in 2020.

Size and results

Median enrollment 274 across the 10 interventional studies. Of the 9 that completed or were terminated, 4 (44%) have results posted.

Watch this landscapeDownload CSVWith an account: a weekly mail of what changed among 12 studies testing doxorubicin in Wilms Tumor, or all of them as a file.
02

Study 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).

Read the 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.

03

Conditions studied

  • Anaplastic Kidney Wilms Tumor
  • Recurrent Kidney Wilms Tumor
  • Stage II Kidney Wilms Tumor
  • Stage III Kidney Wilms Tumor
  • Stage IV Kidney Wilms Tumor

Browse trials for

04

Who can participate

Ages eligible
Up to 30 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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 ) 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 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 . 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 (ECOG) scores of 0, 1 or 2. Use for patients > 16 years of age and Lansky for patients =\< 16 years of age
  • Patients must have a 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 agents (within 4 weeks prior to study enrollment)
  • Peripheral (ANC) >= 750/uL (performed within 7 days prior to enrollment)
  • count >= 75,000/uL (transfusion independent) (performed within 7 days prior to enrollment)
  • >= 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 or radioisotope (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 =\< 1.5 x (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 () (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 (performed within 7 days prior to enrollment)
  • Shortening fraction of >= 27% by echocardiogram, or of >= 50% by radionuclide angiogram (obtained within 21 days prior to enrollment and start of protocol therapy)

Exclusion criteria

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 [CTCAE] version 5.0)
  • 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
  • Lactating females who plan to breastfeed their infants
  • Sexually active patients of who have not agreed to use an effective method for the duration of their study participation
Terms in these criteria, in plain language(21)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Biopsy and archival tissue

A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.

Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.

Relapsed and refractory

Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

ECOG performance status

A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.

0
Fully active, no restrictions.
1
Limited in strenuous activity, but walking and able to do light work, such as housework or office work.
2
Walking and able to look after yourself, but unable to work; up and about more than half of waking hours.
3
Able to look after yourself only in part; in bed or a chair more than half of waking hours.
4
Unable to look after yourself at all; in bed or a chair all day.

Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.

Karnofsky performance status (KPS)

A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.

Studies often ask for 60 or 70 and above. Your doctor gives the score.

Life expectancy

The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

Creatinine clearance (CrCl)

How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.

GFR and eGFR (kidney filtering)

GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².

Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

Metastases

Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.

LVEF (left ventricular ejection fraction)

The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.

CTCAE grade

The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.

1
Mild.
2
Moderate.
3
Severe.
4
Life-threatening.
5
Death due to the event.

“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Reproductive potential

Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.

Criteria about it usually ask for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
256 participants (estimated)

Study arms

  • Experimental
    Arm I (Regimen UH-3)

    See outline in detailed description section.

    Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Bone Scan · Drug: Carboplatin · Procedure: Computed Tomography · Drug: Cyclophosphamide · Drug: Doxorubicin · Drug: Etoposide · Drug: Irinotecan · Procedure: Magnetic Resonance Imaging · Procedure: Positron Emission Tomography · Radiation: Radiation Therapy · Procedure: Transabdominal Ultrasound · Drug: Vincristine · Procedure: X-Ray Imaging

  • Experimental
    Arm II (Regimen ICE/Cyclo/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.

    Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Bone Scan · Drug: Carboplatin · Procedure: Computed Tomography · Drug: Cyclophosphamide · Drug: Etoposide · Drug: Ifosfamide · Procedure: Magnetic Resonance Imaging · Procedure: Positron Emission Tomography · Radiation: Radiation Therapy · Procedure: Surgical Procedure · Drug: Topotecan · Procedure: Transabdominal Ultrasound · Procedure: X-Ray Imaging

Interventions

  • ProcedureBiopsy Procedure

    Undergo a biopsy

    Also known as: Biopsy, BIOPSY_TYPE, Bx

  • ProcedureBiospecimen Collection

    Undergo blood sample collection

    Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

  • ProcedureBone Scan

    Undergo a bone scan

    Also known as: Bone Scintigraphy

  • DrugCarboplatin

    Given IV

    Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, JM8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

  • ProcedureComputed Tomography

    Undergo a CT scan

    Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

  • DrugCyclophosphamide

    Given IV

    Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518, B-518, B518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR 138719, WR- 138719, WR-138719, WR138719

  • DrugDoxorubicin

    Given IV

    Also known as: Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin

  • DrugEtoposide

    Given IV

    Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP 16213, VP-16, VP-16-213, VP-16213, VP16, VP16213

  • DrugIfosfamide

    Given IV

    Also known as: Asta Z 4942, Asta Z-4942, Cyfos, Holoxan, Holoxane, Ifex, IFO, IFO-Cell, Ifolem, Ifomida, Ifomide, Ifosfamidum, Ifoxan, IFX, Iphosphamid, Iphosphamide, Iso-Endoxan, Isoendoxan, Isophosphamide, Mitoxana, MJF 9325, MJF-9325, Naxamide, Seromida, Tronoxal, Z 4942, Z-4942

  • DrugIrinotecan

    Given IV

  • ProcedureMagnetic Resonance Imaging

    Undergo MRI

    Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

  • ProcedurePositron Emission Tomography

    Undergo a PET scan

    Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

  • RadiationRadiation Therapy

    Undergo RT

    Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

  • ProcedureSurgical Procedure

    Undergo surgery

    Also known as: Operation, Surgery, Surgery Type, Surgery, NOS, Surgical, Surgical Intervention, Surgical Interventions, Surgical Procedures, Type of Surgery

  • DrugTopotecan

    Given IV

    Also known as: Hycamptamine, Topotecan Lactone

  • ProcedureTransabdominal Ultrasound

    Undergo abdominal ultrasound

    Also known as: abdominal ultrasound, TUS

  • DrugVincristine

    Given IV

    Also known as: LCR, Leurocristine, VCR, Vincrystine

  • ProcedureX-Ray Imaging

    Undergo a chest x-ray

    Also known as: Conventional X-Ray, Diagnostic Radiology, Medical Imaging, X-Ray, Plain film radiographs, Radiographic Imaging, Radiographic imaging procedure (procedure), Radiography, RG, Static X-Ray, X-Ray

06

What researchers measure

Primary outcomes

  1. Event-free survival (EFS) for stratum 1-3

    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.

    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. EFS for stratum 4

    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.

    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. Overall survival (OS) for stratum 1-4

    The Kaplan-Meier method will be used to estimate OS, defined as the time from study entry until death.

    Time frame: From study entry to death due to any cause, assessed up to 5 years from study entry

Other outcomes

  1. Percentage of patients experiencing grade 3+ renal adverse events

    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.

    Time frame: Up to 30 weeks on average for Stratum 4 only

  2. 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 (ctDNA).

    Time frame: Up to 42 weeks on average for Strata 1-3 and up to 30 weeks on average for Stratum 4

  3. 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.

    Time frame: Based on tissue collected at diagnosis (Strata 1 and 2 only), with outcomes collected up to 5 years after study entry

  4. 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.

    Time frame: Up to 5 years after study entry

  5. 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.

    Time frame: Up to 5 years after study entry

  6. 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.

    Time frame: Nodal information from upfront or delayed nephrectomy, with outcomes collected for up to 5 years after study entry

  7. Rates of usage of intensity-modulated radiation therapy

    Will be reported descriptively for cohorts receiving radiation.

    Time frame: Up to 7 or 30 weeks

  8. Detection and quantification of ctDNA

    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.

    Time frame: Up to 42 weeks on average for Strata 1-3 and up to 30 weeks on average for Stratum 4

07

Study locations

192 of 205 sites recruiting

Showing the first 100 of 205 sites across 6 countries. Choose a country and city above to see the rest.

08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 25, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT04322318
Lead sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Mar 26, 2020
Start date
Oct 19, 2020
Primary completion
Jul 1, 2027 (estimated)
Completion
Jul 1, 2027 (estimated)
Last update
Aug 25, 2026

Study contacts

James I Geller
principal investigator · Children's Oncology Group

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Interested in this study?

Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.

No contact was published for this record. The registry link below has the sponsor’s details.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drugs tested here: Doxorubicin · Ifosfamide · Irinotecan · Topotecan · Vincristine

Other studies in this condition

Wilms Tumor →

Other studies from this sponsor

Children's Oncology Group →

Start the discussion