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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00352534




Registration number
NCT00352534
Ethics application status
Date submitted
13/07/2006
Date registered
14/07/2006
Date last updated
24/04/2024

Titles & IDs
Public title
Vincristine, Dactinomycin, and Doxorubicin With or Without Radiation Therapy or Observation Only in Treating Younger Patients Who Are Undergoing Surgery for Newly Diagnosed Stage I, Stage II, or Stage III Wilms' Tumor
Scientific title
Treatment for Very Low and Standard Risk Favorable Histology Wilms Tumor
Secondary ID [1] 0 0
NCI-2009-01067
Secondary ID [2] 0 0
AREN0532
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stage I Kidney Wilms Tumor 0 0
Stage II Kidney Wilms Tumor 0 0
Stage III Kidney Wilms Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Children's - Other
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - 3-Dimensional Conformal Radiation Therapy
Treatment: Surgery - Biospecimen Collection
Treatment: Surgery - Chest Radiography
Treatment: Surgery - Computed Tomography
Treatment: Other - Dactinomycin
Treatment: Drugs - Doxorubicin Hydrochloride
Treatment: Surgery - Echocardiography
Treatment: Surgery - Magnetic Resonance Imaging
Treatment: Surgery - Therapeutic Conventional Surgery
Treatment: Surgery - Ultrasound Imaging
Treatment: Drugs - Vincristine Sulfate

Experimental: Stratum I (very low-risk disease) - Patients undergo nephrectomy only. If they meet criteria, they are then observed periodically for 5 years. Patients with recurrent disease undergo surgery (immediate or delayed) and receive chemotherapy as in stratum III. Patients with no metachronous renal disease receive radiotherapy. Patients with metachronous disease undergo renal-sparing surgery and chemotherapy as in stratum III, but no radiotherapy. Treatment continues for up to 25 weeks. Additionally, patients undergo chest X-ray, CT or MRI, ultrasound, echocardiography, and blood sample collection throughout the study.

Experimental: Stratum II (standard-risk, stage I or II) - Patients undergo nephrectomy. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1, every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 doses of doxorubicin. Treatment continues for up to 25 weeks. Additionally, patients undergo chest X-ray, CT or MRI, ultrasound, echocardiography, and blood sample collection throughout the study.

Experimental: Stratum III (standard-risk, stage III) - Patients undergo nephrectomy, if feasible, or biopsy. For patients who undergo biopsy only, definitive surgery is undertaken at week 7 or 13. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1 every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 dose of doxorubicin hydrochloride. Patients undergo radiotherapy over 5-7 days after nephrectomy. Treatment continues for up to 25 weeks. Additionally, patients undergo chest X-ray, CT or MRI, ultrasound, echocardiography, and blood sample collection throughout the study.


Treatment: Other: 3-Dimensional Conformal Radiation Therapy
Patients undergo radiotherapy

Treatment: Surgery: Biospecimen Collection
Undergo blood sample collection

Treatment: Surgery: Chest Radiography
Undergo chest X-ray

Treatment: Surgery: Computed Tomography
Undergo CT

Treatment: Other: Dactinomycin
Given IV

Treatment: Drugs: Doxorubicin Hydrochloride
Given IV

Treatment: Surgery: Echocardiography
Undergo echocardiography

Treatment: Surgery: Magnetic Resonance Imaging
Undergo MRI

Treatment: Surgery: Therapeutic Conventional Surgery
Undergo surgery

Treatment: Surgery: Ultrasound Imaging
Undergo ultrasound

Treatment: Drugs: Vincristine Sulfate
Given IV
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Surgery
Intervention code [3] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event Free Survival Probability
Timepoint [1] 0 0
4 years
Primary outcome [2] 0 0
Overall Survival (OS) Probability
Timepoint [2] 0 0
4 years
Secondary outcome [1] 0 0
Incidence of Contralateral Kidney Lesions
Timepoint [1] 0 0
During follow-up
Secondary outcome [2] 0 0
Incidence of Renal Failure
Timepoint [2] 0 0
During follow-up

Eligibility
Key inclusion criteria
* Histologically confirmed Wilms' tumor

* Newly diagnosed stage I-III disease
* Favorable histology
* No moderate- or high-risk Wilms' predisposition syndromes
* Must meet 1 of the following disease stratification categories:

* Very low-risk disease

* Stage I disease
* Age < 2 years
* Tumor weight < 550 g
* Regional lymph nodes histologically negative (must have been sampled)
* No pulmonary metastases on CT scan of chest
* No synchronous bilateral Wilms tumors (Stage V)
* Not predisposed to develop bilateral Wilms tumors, defined as unilateral Wilms tumor and any of the following:

* Aniridia
* Beckwith-Wiedemann syndrome
* Simpson-Golabi-Behmel syndrome
* Denys-Drash syndrome or other associated genito-urinary anomalies
* Multicentric WT or unilateral WT with contralateral nephrogenic rest(s) in a child < 1 year of age
* Diffuse hyperplastic perilobar nephroblastomatosis
* Standard-risk disease meeting 1 of the following criteria:

* Disease does not require radiotherapy

* LOH at chromosomes 1p and 16q for stage I or II
* Stage I disease meeting 1 of the following criteria:

* Age = 2 years to age < 30 years
* Tumor weight = 500 g
* Stage II disease

* Age < 30 years
* Any tumor weight
* Disease requires radiotherapy

* No LOH at chromosomes 1p and 16q*
* Stage III disease
* Must be enrolled on protocol COG-AREN03B2
* Karnofsky performance status (PS) 50-100% for patients > 16 years old
* Lansky PS 50-100% for patients = 16 years old
* Bilirubin (direct) = 1.5 times upper limit of normal (ULN)
* AST or ALT < 2.5 times ULN
* Shortening fraction = 27% by echocardiogram OR ejection fraction = 50% by radionuclide angiogram (standard-risk disease)
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patient must use effective contraception
* No prior tumor-directed chemotherapy or radiotherapy

* Patients transferring from AREN03B2 with LOH 1p and 16q allowed
Minimum age
No limit
Maximum age
29 Years
Sex
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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/11/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
8/04/2025
Actual
Sample size
Target
Accrual to date
Final
808
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,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
Queensland Children's Hospital - South Brisbane
Recruitment hospital [6] 0 0
Women's and Children's Hospital-Adelaide - North Adelaide
Recruitment hospital [7] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [8] 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
3052 - Parkville
Recruitment postcode(s) [7] 0 0
6008 - Perth
Recruitment outside Australia
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United States of America
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Alabama
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Arizona
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Arkansas
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California
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Connecticut
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Delaware
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District of Columbia
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Florida
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Georgia
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Hawaii
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Idaho
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Illinois
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Indiana
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Iowa
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Kansas
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Kentucky
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Maine
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New Mexico
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New York
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Oregon
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Pennsylvania
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Rhode Island
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South Carolina
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Tennessee
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West Virginia
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Wisconsin
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Alberta
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British Columbia
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Manitoba
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Newfoundland and Labrador
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Ontario
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Saskatchewan
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Israel
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Petah Tikua
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New Zealand
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Auckland
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New Zealand
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Christchurch
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Puerto Rico
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San Juan
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Switzerland
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Bern

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 is studying vincristine, dactinomycin, and doxorubicin with or without radiation therapy or observation only to see how well they work in treating patients undergoing surgery for newly diagnosed stage I, stage II, or stage III Wilms' tumor. Drugs used in chemotherapy, such as vincristine, dactinomycin, and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors.Giving these treatments after surgery may kill any tumor cells that remain after surgery. Sometimes, after surgery, the tumor may not need additional treatment until it progresses. In this case, observation may be sufficient.
Trial website
https://clinicaltrials.gov/study/NCT00352534
Trial related presentations / publications
Dix DB, Fernandez CV, Chi YY, Mullen EA, Geller JI, Gratias EJ, Khanna G, Kalapurakal JA, Perlman EJ, Seibel NL, Ehrlich PF, Malogolowkin M, Anderson J, Gastier-Foster J, Shamberger RC, Kim Y, Grundy PE, Dome JS; AREN0532 and AREN0533 study committees. Augmentation of Therapy for Combined Loss of Heterozygosity 1p and 16q in Favorable Histology Wilms Tumor: A Children's Oncology Group AREN0532 and AREN0533 Study Report. J Clin Oncol. 2019 Oct 20;37(30):2769-2777. doi: 10.1200/JCO.18.01972. Epub 2019 Aug 26.
Fernandez CV, Mullen EA, Chi YY, Ehrlich PF, Perlman EJ, Kalapurakal JA, Khanna G, Paulino AC, Hamilton TE, Gow KW, Tochner Z, Hoffer FA, Withycombe JS, Shamberger RC, Kim Y, Geller JI, Anderson JR, Grundy PE, Dome JS. Outcome and Prognostic Factors in Stage III Favorable-Histology Wilms Tumor: A Report From the Children's Oncology Group Study AREN0532. J Clin Oncol. 2018 Jan 20;36(3):254-261. doi: 10.1200/JCO.2017.73.7999. Epub 2017 Dec 6. Erratum In: J Clin Oncol. 2019 Oct 10;37(29):2710. doi: 10.1200/JCO.19.02265.
Fernandez CV, Perlman EJ, Mullen EA, Chi YY, Hamilton TE, Gow KW, Ferrer FA, Barnhart DC, Ehrlich PF, Khanna G, Kalapurakal JA, Bocking T, Huff V, Tian J, Geller JI, Grundy PE, Anderson JR, Dome JS, Shamberger RC. Clinical Outcome and Biological Predictors of Relapse After Nephrectomy Only for Very Low-risk Wilms Tumor: A Report From Children's Oncology Group AREN0532. Ann Surg. 2017 Apr;265(4):835-840. doi: 10.1097/SLA.0000000000001716.
Public notes

Contacts
Principal investigator
Name 0 0
Elizabeth A Mullen
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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00352534