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Combination Chemotherapy and Surgery in Treating Young Patients With Wilms Tumor

Treatment for Patients With Bilateral, Multicentric, or Bilaterally-Predisposed Unilateral Wilms Tumor

Status
Completed
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00945009
Enrollment
249
Registered
2009-07-23
Start date
2009-08-24
Completion date
2026-03-31
Last updated
2026-06-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Adult Kidney Wilms Tumor, Beckwith-Wiedemann Syndrome, Childhood Kidney Wilms Tumor, Diffuse Hyperplastic Perilobar Nephroblastomatosis, Rhabdoid Tumor of the Kidney, Stage III Kidney Wilms Tumor, Stage II Kidney Wilms Tumor, Stage I Kidney Wilms Tumor, Stage IV Kidney Wilms Tumor, Stage V Kidney Wilms Tumor

Brief summary

This phase III trial studies how well combination chemotherapy and surgery work in treating young patients with Wilms tumor. Drugs used in chemotherapy 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. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving it after surgery may kill any tumor cells that remain after surgery.

Detailed description

OBJECTIVES: I. To improve 4-year event-free survival (EFS) to 73% for young patients with bilateral Wilms tumor (BWT). II. To prevent complete removal of at least one kidney in 50% of patients with BWT by using prenephrectomy 3-drug chemotherapy induction with vincristine (vincristine sulfate), dactinomycin, and doxorubicin (doxorubicin hydrochloride). III. To evaluate the efficacy of chemotherapy in preserving renal units in children with diffuse hyperplastic perilobar nephroblastomatosis (DHPLN) and preventing Wilms tumor development. IV. To facilitate partial nephrectomy in lieu of nephrectomy in 25% of children with unilateral tumors and aniridia, Beckwith-Wiedemann syndrome (BWS), hemihypertrophy or other overgrowth syndromes, by using prenephrectomy 2-drug chemotherapy induction with vincristine and dactinomycin. V. To have 75% of patients with BWT undergo definitive surgical treatment by 12 weeks after initiation of chemotherapy. OUTLINE: Patients are assigned to 1 of 3 arms. ARM 1 (Bilateral Wilms Tumors): Patients start with three drug chemotherapy (Regimen VAD; vincristine, dactinomycin and doxorubicin) and are evaluated and six and 12 weeks for feasibility of undergoing a partial nephrectomy/renal sparing surgery. At week 12 definitive surgery takes place followed by chemotherapy and radiation therapy based on histology and stage. Treatment continues for 25 or 31 weeks depending on histology. Patients are followed for up to 10 years following end of therapy. ARM 2 (Unilateral High Risk tumors bilaterally predisposed): Patients start with either 2 drug or three drug chemotherapy (Regimen VA, VAD) and are evaluated a 6 and 12 weeks for feasibility of undergoing a partial nephrectomy. At week 12 definitive surgery takes place followed by chemotherapy. ARM 3 (DHPLN): Patients with this rare disease are diagnosed based on cross-sectional imaging characteristics and undergo 2 drug chemotherapy (Regimen;VA). Patients are reassessed at 6 weeks and 12 weeks. If disease has responded or stayed stable chemotherapy is completed for 19 weeks (Regimen EE4A). If disease has progress a biopsy is performed to assess histology and adjust therapy based on the biopsy. This therapy may include, nephrectomy, chemotherapy or radiation therapy. VAD REGIMEN: Patients receive vincristine sulfate intravenously (IV) over 1 minute on days 1, 8, 15, 22, 29, and 36 (weeks 1-6) and dactinomycin IV and doxorubicin hydrochloride IV over 15-120 minutes on days 1 and 22 (weeks 1 and 4). EE4A REGIMEN: Patients receive vincristine sulfate IV over 1 minute on days 1, 8, 15, 22, 29, and 36 (weeks 1-6) and dactinomycin IV over 1-5 minutes on days 1 and 22 (weeks 1 and 4). After completion of study treatment, patients are followed up periodically for 10 years.

Interventions

BIOLOGICALDactinomycin

Given IV

DRUGDoxorubicin Hydrochloride

Given IV

RADIATIONRadiation Therapy

Undergo radiation therapy

PROCEDURETherapeutic Conventional Surgery

Undergo surgical resection

DRUGVincristine Sulfate

Given IV

Sponsors

Children's Oncology Group
Lead SponsorNETWORK
National Cancer Institute (NCI)
CollaboratorNIH

Study design

Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
No minimum to 29 Years
Healthy volunteers
No

Inclusion criteria

* The patient must have one of the following conditions to be eligible: * Synchronous bilateral Wilms tumors\*\*; or * Unilateral Wilms tumor and aniridia, Beckwith-Wiedemann Syndrome, idiopathic hemihypertrophy, Simpson-Golabi-Behmel-Syndrome, Denys-Drash Syndrome or other associated genitourinary anomalies associated with bilateral Wilms tumor, such as hypospadias and undescended testis (to be eligible, these patients must not undergo any nephrectomy at diagnosis; note-horseshoe kidney is not associated with bilateral Wilms tumor and these patients should go on the appropriate unilateral Wilms tumor study); or * Multicentric Wilms tumor (any age) (to be eligible, these patients must not undergo any nephrectomy at diagnosis); or * Unilateral Wilms tumor with contralateral nephrogenic rest(s) (any size) in a child under one year of age (to be eligible, these patients must not undergo any nephrectomy at diagnosis); or * Diffuse hyperplastic perilobar nephroblastomatosis (unilateral or bilateral) defined by central radiological review; or * Wilms tumor arising in a solitary kidney (patients with metachronous Wilms tumor are not eligible) * The AREN0534 study uses the guideline that Wilms tumor with a single lesion 1 cm or greater in the contralateral kidney or multiple lesions (of any size) in the contralateral kidney should be treated on the synchronous bilateral Wilms tumor stratum; patients with an isolated lesion less than 1 cm in the contralateral kidney should be treated on the appropriate study for unilateral Wilms tumor OR on the unilateral Wilms tumor/contralateral nephrogenic rest stratum of this study if they have not undergone nephrectomy and are under one year of age * Loss of heterozygosity (LOH) results-which are used in the unilateral Wilms tumor studies-are not a requirement for enrollment on AREN0534; blood samples can be submitted but will not be used to direct AREN0534 therapy * Specimens/materials must be submitted for central review by day 7; for enrollment on AREN0534, unless a biopsy was done, the submission requirements at enrollment on AREN03B2 refer to imaging studies; tissue samples are only required if a surgical procedure (biopsy or nephrectomy) was performed at the time of enrollment on AREN03B2 * Patients must begin protocol therapy on AREN0534 by day 14 following surgery or diagnosis by initial computed tomography (CT)/magnetic resonance imaging (MRI), unless medically contraindicated * Karnofsky performance status must be \>= 50% for patients \> 16 years of age and Lansky performance status must be \>= 50% (for patients =\< 16 years of age * Patients must not have received systemic chemotherapy or radiation therapy prior to treatment on this study * Patients with unilateral Wilms tumor and aniridia, Beckwith-Wiedemann Syndrome, idiopathic hemihypertrophy, Simpson-Golabi-Behmel-Syndrome, Denys-Drash Syndrome or other associated genitourinary anomalies; or multicentric or unilateral Wilms tumor with contralateral nephrogenic rest(s) (any size) in a child under 1 year of age who undergo a nephrectomy at diagnosis are not eligible for this study and should be directed to a unilateral Wilms tumor study * Total bilirubin =\< 1.5 times upper limit of normal (ULN) for age * Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) \< 2.5 times upper limit of normal (ULN) for age * Shortening fraction \>= 27% by echocardiogram, OR ejection fraction \>= 50% by radionuclide angiogram * (Cardiac function does not need to be assessed in patients who will not receive doxorubicin as part of their initial therapy on this study \[i.e., patients who start on regimen EE-4A\]) * Female patients of childbearing age must have a negative pregnancy test * Female patients who are lactating must agree to stop breastfeeding * Sexually active patients of childbearing potential must agree to use effective contraception * All patients and/or their parents or legal guardians must sign a written informed consent * All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met * No concurrent aprepitant

Design outcomes

Primary

MeasureTime frameDescription
Event-Free Survival (EFS)4 years from study enrollmentProbability of no relapse, secondary malignancy, or death whichever occurs first
Kidney Preservation After Preoperative Chemotherapy12 weeks from study entryPrevention of complete removal of at least one kidney in 50% of patients with bilateral Wilms tumor (BWT).
Number of Patients Without Complete Removal of at Least One Kidney12 weeks from the study entryTo evaluate the efficacy of chemotherapy in preserving renal units in children with diffuse hyperplastic perilobar nephroblastomatosis (DHPLN) and preventing Wilms tumor development.
Percentage of Patients Who Experienced Partial Nephrectomy After Preoperative Chemotherapy12 weeks from study entryPercentage of patients who experienced partial nephrectomy in lieu of nephrectomy in 25% of children with unilateral tumors and aniridia, Beckwith-Wiedemann syndrome (BWS), hemihypertrophy or other overgrowth syndromes, by using prenephrectomy 2-drug chemotherapy induction with vincristine and dactinomycin.
Percentage of Patients Who Had Definitive Surgical Treatment12 weeks from study entryPercentage of Bilateral Wilms Tumor (BWT) patients who undergo definitive surgery by week 12 after initiation of chemotherapy.

Countries

Australia, Canada, Israel, New Zealand, Puerto Rico, United States

Contacts

PRINCIPAL_INVESTIGATORPeter F Ehrlich

Children's Oncology Group

Participant flow

Participants by arm

ArmCount
Arm 1 (Bilateral Wilms Tumors)
Patients start with three drug chemotherapy (Regimen VAD; vincristine, dactinomycin and doxorubicin) and are evaluated and six and 12 weeks for feasibility of undergoing a partial nephrectomy/renal sparing surgery. At week 12 definitive surgery takes place followed by chemotherapy and radiation therapy based on histology and stage. Treatment continues for 25 or 31 weeks depending on histology. Patients are followed for up to 10 years following end of therapy. Dactinomycin: Given IV Doxorubicin Hydrochloride: Given IV Radiation Therapy: Undergo radiation therapy Therapeutic Conventional Surgery: Undergo surgical resection Vincristine Sulfate: Given IV
201
Arm 2 (Unilateral High Risk Tumors Bilaterally Predisposed)
Patients start with either 2 drug or three drug chemotherapy (Regimen VA, VAD) and are evaluated a 6 and 12 weeks for feasibility of undergoing a partial nephrectomy. At week 12 definitive surgery takes place followed by chemotherapy. Dactinomycin: Given IV Doxorubicin Hydrochloride: Given IV Radiation Therapy: Undergo radiation therapy Therapeutic Conventional Surgery: Undergo surgical resection Vincristine Sulfate: Given IV
39
Arm 3 (DHPLN)
Patients with this rare disease are diagnosed based on cross-sectional imaging characteristics and undergo 2 drug chemotherapy (Regimen;VA). Patients are reassessed at 6 weeks and 12 weeks. If disease has responded or stayed stable chemotherapy is completed for 19 weeks (Regimen EE4A). If disease has progress a biopsy is performed to assess histology and adjust therapy based on the biopsy. This therapy may include, nephrectomy, chemotherapy or radiation therapy. Dactinomycin: Given IV Doxorubicin Hydrochloride: Given IV Radiation Therapy: Undergo radiation therapy Therapeutic Conventional Surgery: Undergo surgical resection Vincristine Sulfate: Given IV
9
Total249

Baseline characteristics

CharacteristicArm 1 (Bilateral Wilms Tumors)Arm 2 (Unilateral High Risk Tumors Bilaterally Predisposed)Arm 3 (DHPLN)Total
Age, Continuous32.03 Months
STANDARD_DEVIATION 22.22
34.70 Months
STANDARD_DEVIATION 22.12
13.26 Months
STANDARD_DEVIATION 8.7
31.78 Months
STANDARD_DEVIATION 22.12
Ethnicity (NIH/OMB)
Hispanic or Latino
27 Participants3 Participants0 Participants30 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
168 Participants35 Participants8 Participants211 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
6 Participants1 Participants1 Participants8 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants1 Participants0 Participants1 Participants
Race (NIH/OMB)
Asian
3 Participants1 Participants0 Participants4 Participants
Race (NIH/OMB)
Black or African American
31 Participants5 Participants1 Participants37 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
25 Participants3 Participants1 Participants29 Participants
Race (NIH/OMB)
White
142 Participants29 Participants7 Participants178 Participants
Sex: Female, Male
Female
119 Participants23 Participants5 Participants147 Participants
Sex: Female, Male
Male
82 Participants16 Participants4 Participants102 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
10 / 1890 / 360 / 9
other
Total, other adverse events
34 / 1891 / 360 / 9
serious
Total, serious adverse events
12 / 1891 / 360 / 9

Outcome results

Primary

Event-Free Survival (EFS)

Probability of no relapse, secondary malignancy, or death whichever occurs first

Time frame: 4 years from study enrollment

Population: All eligible BWT patients. 6 patients were excluded due to ineligibility and 6 patients were excluded due to protocol violation.

ArmMeasureValue (MEAN)
Arm 1 (Bilateral Wilms Tumors)Event-Free Survival (EFS)0.82 Probability
Primary

Kidney Preservation After Preoperative Chemotherapy

Prevention of complete removal of at least one kidney in 50% of patients with bilateral Wilms tumor (BWT).

Time frame: 12 weeks from study entry

Population: Eligible and evaluable Bilateral Wilms Tumor patients who completed pre-nephrectomy chemotherapy (VAD). 49 patients who did not complete VAD were excluded.

ArmMeasureValue (NUMBER)
Arm 1 (Bilateral Wilms Tumors)Kidney Preservation After Preoperative Chemotherapy39 Percentage of patients
Primary

Number of Patients Without Complete Removal of at Least One Kidney

To evaluate the efficacy of chemotherapy in preserving renal units in children with diffuse hyperplastic perilobar nephroblastomatosis (DHPLN) and preventing Wilms tumor development.

Time frame: 12 weeks from the study entry

Population: Eligible and evaluable patients with diffuse hyperplastic perilobar nephroblastomatosis (DPHLN).

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Arm 1 (Bilateral Wilms Tumors)Number of Patients Without Complete Removal of at Least One Kidney7 Participants
Primary

Percentage of Patients Who Experienced Partial Nephrectomy After Preoperative Chemotherapy

Percentage of patients who experienced partial nephrectomy in lieu of nephrectomy in 25% of children with unilateral tumors and aniridia, Beckwith-Wiedemann syndrome (BWS), hemihypertrophy or other overgrowth syndromes, by using prenephrectomy 2-drug chemotherapy induction with vincristine and dactinomycin.

Time frame: 12 weeks from study entry

Population: Eligible and evaluable patients with unilateral high risk tumors who had partial or complete nephrectomy. 16 total patients were excluded (1 ineligible, 1 inevaluable, 1 violated protocol, and 13 did not have definitive surgery (partial or complete nephrectomy).

ArmMeasureValue (NUMBER)
Arm 1 (Bilateral Wilms Tumors)Percentage of Patients Who Experienced Partial Nephrectomy After Preoperative Chemotherapy57 percentage of patients
Primary

Percentage of Patients Who Had Definitive Surgical Treatment

Percentage of Bilateral Wilms Tumor (BWT) patients who undergo definitive surgery by week 12 after initiation of chemotherapy.

Time frame: 12 weeks from study entry

Population: Eligible and evaluable Bilateral Wilms Tumor patients. 6 patients were excluded due to ineligible and 6 patients were excluded due to protocol violation.

ArmMeasureValue (NUMBER)
Arm 1 (Bilateral Wilms Tumors)Percentage of Patients Who Had Definitive Surgical Treatment85 percentage of participants

Source: ClinicalTrials.gov · Data processed: Jun 4, 2026