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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00945009




Registration number
NCT00945009
Ethics application status
Date submitted
22/07/2009
Date registered
22/07/2009
Date last updated
11/02/2019

Titles & IDs
Public title
Combination Chemotherapy and Surgery in Treating Young Patients With Wilms Tumor
Scientific title
Treatment for Patients With Bilateral, Multicentric, or Bilaterally-Predisposed Unilateral Wilms Tumor
Secondary ID [1] 0 0
NCI-2011-01953
Secondary ID [2] 0 0
AREN0534
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Adult Kidney Wilms Tumor 0 0
Beckwith-Wiedemann Syndrome 0 0
Childhood Kidney Wilms Tumor 0 0
Diffuse Hyperplastic Perilobar Nephroblastomatosis 0 0
Hemihypertrophy 0 0
Rhabdoid Tumor of the Kidney 0 0
Stage I Kidney Wilms Tumor 0 0
Stage II Kidney Wilms Tumor 0 0
Stage III Kidney Wilms Tumor 0 0
Stage IV Kidney Wilms Tumor 0 0
Stage V Kidney Wilms Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Children's - Other
Cancer 0 0 0 0
Kidney
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Dactinomycin
Treatment: Drugs - Doxorubicin Hydrochloride
Treatment: Other - Radiation Therapy
Treatment: Surgery - Therapeutic Conventional Surgery
Treatment: Drugs - Vincristine Sulfate

Experimental: 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.

Experimental: 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.

Experimental: 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.


Other interventions: Dactinomycin
Given IV

Treatment: Drugs: Doxorubicin Hydrochloride
Given IV

Treatment: Other: Radiation Therapy
Undergo radiation therapy

Treatment: Surgery: Therapeutic Conventional Surgery
Undergo surgical resection

Treatment: Drugs: Vincristine Sulfate
Given IV

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Treatment: Other
Intervention code [4] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-Free Survival (EFS) - Probability of no relapse, secondary malignancy, or death whichever occurs first
Timepoint [1] 0 0
4 years from study enrollment
Primary outcome [2] 0 0
Kidney Preservation After Preoperative Chemotherapy - Prevention of complete removal of at least one kidney in 50% of patients with bilateral Wilms tumor (BWT).
Timepoint [2] 0 0
12 weeks from study entry
Primary outcome [3] 0 0
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.
Timepoint [3] 0 0
12 weeks from the study entry
Primary outcome [4] 0 0
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.
Timepoint [4] 0 0
12 weeks from study entry
Primary outcome [5] 0 0
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.
Timepoint [5] 0 0
12 weeks from study entry

Eligibility
Key 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
Minimum age
No limit
Maximum age
29 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [2] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [3] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [4] 0 0
Royal Children's Hospital-Brisbane - Herston
Recruitment hospital [5] 0 0
Lady Cilento Children's Hospital - South Brisbane
Recruitment hospital [6] 0 0
Women's and Children's Hospital-Adelaide - North Adelaide
Recruitment hospital [7] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
5006 - North Adelaide
Recruitment postcode(s) [6] 0 0
6008 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Connecticut
Country [7] 0 0
United States of America
State/province [7] 0 0
Delaware
Country [8] 0 0
United States of America
State/province [8] 0 0
District of Columbia
Country [9] 0 0
United States of America
State/province [9] 0 0
Florida
Country [10] 0 0
United States of America
State/province [10] 0 0
Georgia
Country [11] 0 0
United States of America
State/province [11] 0 0
Idaho
Country [12] 0 0
United States of America
State/province [12] 0 0
Illinois
Country [13] 0 0
United States of America
State/province [13] 0 0
Indiana
Country [14] 0 0
United States of America
State/province [14] 0 0
Iowa
Country [15] 0 0
United States of America
State/province [15] 0 0
Kentucky
Country [16] 0 0
United States of America
State/province [16] 0 0
Louisiana
Country [17] 0 0
United States of America
State/province [17] 0 0
Maine
Country [18] 0 0
United States of America
State/province [18] 0 0
Maryland
Country [19] 0 0
United States of America
State/province [19] 0 0
Massachusetts
Country [20] 0 0
United States of America
State/province [20] 0 0
Michigan
Country [21] 0 0
United States of America
State/province [21] 0 0
Minnesota
Country [22] 0 0
United States of America
State/province [22] 0 0
Mississippi
Country [23] 0 0
United States of America
State/province [23] 0 0
Missouri
Country [24] 0 0
United States of America
State/province [24] 0 0
Nevada
Country [25] 0 0
United States of America
State/province [25] 0 0
New Hampshire
Country [26] 0 0
United States of America
State/province [26] 0 0
New Jersey
Country [27] 0 0
United States of America
State/province [27] 0 0
New Mexico
Country [28] 0 0
United States of America
State/province [28] 0 0
New York
Country [29] 0 0
United States of America
State/province [29] 0 0
North Carolina
Country [30] 0 0
United States of America
State/province [30] 0 0
North Dakota
Country [31] 0 0
United States of America
State/province [31] 0 0
Ohio
Country [32] 0 0
United States of America
State/province [32] 0 0
Oklahoma
Country [33] 0 0
United States of America
State/province [33] 0 0
Oregon
Country [34] 0 0
United States of America
State/province [34] 0 0
Pennsylvania
Country [35] 0 0
United States of America
State/province [35] 0 0
South Carolina
Country [36] 0 0
United States of America
State/province [36] 0 0
South Dakota
Country [37] 0 0
United States of America
State/province [37] 0 0
Tennessee
Country [38] 0 0
United States of America
State/province [38] 0 0
Texas
Country [39] 0 0
United States of America
State/province [39] 0 0
Utah
Country [40] 0 0
United States of America
State/province [40] 0 0
Vermont
Country [41] 0 0
United States of America
State/province [41] 0 0
Virginia
Country [42] 0 0
United States of America
State/province [42] 0 0
Washington
Country [43] 0 0
United States of America
State/province [43] 0 0
West Virginia
Country [44] 0 0
United States of America
State/province [44] 0 0
Wisconsin
Country [45] 0 0
Canada
State/province [45] 0 0
Alberta
Country [46] 0 0
Canada
State/province [46] 0 0
British Columbia
Country [47] 0 0
Canada
State/province [47] 0 0
Manitoba
Country [48] 0 0
Canada
State/province [48] 0 0
Nova Scotia
Country [49] 0 0
Canada
State/province [49] 0 0
Ontario
Country [50] 0 0
Canada
State/province [50] 0 0
Quebec
Country [51] 0 0
Canada
State/province [51] 0 0
Saskatchewan
Country [52] 0 0
Israel
State/province [52] 0 0
Petah Tikua
Country [53] 0 0
New Zealand
State/province [53] 0 0
Auckland
Country [54] 0 0
New Zealand
State/province [54] 0 0
Christchurch
Country [55] 0 0
Puerto Rico
State/province [55] 0 0
San Juan

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00945009
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Peter Ehrlich
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications