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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00002611




Registration number
NCT00002611
Ethics application status
Date submitted
1/11/1999
Date registered
27/01/2003
Date last updated
25/02/2021

Titles & IDs
Public title
Combination Chemotherapy Alone or With Radiation Therapy in Treating Children With Kidney Cancer
Scientific title
NATIONAL WILMS TUMOR STUDY-5 -- THERAPEUTIC TRIAL AND BIOLOGY STUDY
Secondary ID [1] 0 0
COG-Q9401
Secondary ID [2] 0 0
9440
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Kidney Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Children's - Other

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - dactinomycin
Other interventions - filgrastim
Treatment: Drugs - cyclophosphamide
Treatment: Drugs - doxorubicin hydrochloride
Treatment: Drugs - etoposide
Treatment: Drugs - vincristine sulfate
Treatment: Surgery - conventional surgery
Treatment: Other - radiation therapy

Active Comparator: Stratum 1 - Stage I favorable histology (FH) Wilms' tumor, under 24 months of age, and tumor weight less than 550 g: After conventional surgery (nephrectomy), patients receive regimen EE-4A comprising dactinomycin (DACT) IV weekly on weeks 0, 3, 6, 9, 12, 15, and 18 and vincristine sulfate (VCR) IV weekly on weeks 1-10, 12, 15, and 18.

Active Comparator: Stratum 2 - Stage I FH Wilms' tumor and age 24 months and over or tumor weight at least 550 g; stage I focal anaplastic (FA) or diffuse anaplastic (DA) Wilms' tumor: Patients receive regimen EE-4A comprising dactinomycin (DACT) IV weekly on weeks 0, 3, 6, 9, 12, 15, and 18 and vincristine sulfate (VCR) IV weekly on weeks 1-10, 12, 15, and 18.

Active Comparator: Stratum 3 - Stage II FH Wilms' tumor: Patients receive regimen EE-4A comprising dactinomycin (DACT) IV weekly on weeks 0, 3, 6, 9, 12, 15, and 18 and vincristine sulfate (VCR) IV weekly on weeks 1-10, 12, 15, and 18.

Active Comparator: Stratum 4 - Stage III FH Wilms' tumor; stage II or III FA Wilms' tumor: After conventional surgery (nephrectomy), patients receive regimen DD-4A comprising dactinomycin DACT IV weekly on weeks 0, 6, 12, 18, and 24; doxorubicin hydrochloride IV weekly on weeks 3, 9, 15, and 21; and vincristine sulfate VCR IV weekly on weeks 1-10, 12, 15, 18, 21, and 24. Patients also undergo abdominal radiation therapy.

Active Comparator: Stratum 5 - Stage IV FH or FA Wilms' tumor: patients receive regimen DD-4A comprising dactinomycin DACT IV weekly on weeks 0, 6, 12, 18, and 24; doxorubicin hydrochloride IV weekly on weeks 3, 9, 15, and 21; and vincristine sulfate VCR IV weekly on weeks 1-10, 12, 15, 18, 21, and 24. Patients also undergo abdominal radiation therapy, and whole lung radiation therapy (at the discretion of the investigator).

Active Comparator: Stratum 6 - Stage V FH, FA, or DA Wilms' tumor: After bilateral conventional surgery (biopsy), patients with FH receive chemotherapy as in stratum 1 (dactinomycin IV weeks 0, 3, 6, 9, 12, 15, and 18 and vincristine sulfate IV weeks 1-10, 12, 15, and 18) or 4 (dactinomycin IV weeks 0, 6, 12, 18, and 24; doxorubicin hydrochloride IV weeks 3, 9, 15, and 21; and vincristine sulfate VCR IV weeks 1-10, 12, 15, 18, 21, and 24). Patients with FA or DA receive chemotherapy as in stratum 7 (vincristine sulfate VCR IV weeks 1, 2, 4-8, 10-13, 18, and 24; cyclophosphamide sulfate (CTX) IV over 1 hour on days 1-3 of weeks 6, 12, 18, and 24 and on days 1-5 of weeks 3, 9, 15, and 21; doxorubicin hydrochloride IV (beginning after CTX infusion) weeks 0, 6, 12, 18, and 24; and etoposide (VP-16) IV over 1 hour (beginning after CTX infusion) on days 1-5 of weeks 3, 9, 15, and 21. Filgrastim (G-CSF) is administered subcutaneously (SC) beginning 24 hours after completion of chemotherapy.

Active Comparator: Stratum 7 - Stages I-IV clear cell sarcoma): After conventional surgery (nephrectomy), patients receive vincristine sulfate VCR IV weekly on weeks 1, 2, 4-8, 10-13, 18, and 24; cyclophosphamide sulfate (CTX) IV over 1 hour on days 1-3 of weeks 6, 12, 18, and 24 and on days 1-5 of weeks 3, 9, 15, and 21; doxorubicin hydrochloride IV (beginning after CTX infusion) weekly on weeks 0, 6, 12, 18, and 24; and etoposide (VP-16) IV over 1 hour (beginning after CTX infusion) on days 1-5 of weeks 3, 9, 15, and 21. Filgrastim (G-CSF) is administered subcutaneously (SC) beginning 24 hours after completion of chemotherapy and continuing until blood counts recover. Patients also undergo abdominal radiotherapy and whole lung radiotherapy (if pulmonary metastases are present).

Active Comparator: Stratum 8 - Stages II-IV DA Wilms' tumor: After conventional surgery (nephrectomy), Patients receive treatment as in stratum 7 (patients receive vincristine sulfate VCR IV weekly on weeks 1, 2, 4-8, 10-13, 18, and 24; cyclophosphamide sulfate (CTX) IV over 1 hour on days 1-3 of weeks 6, 12, 18, and 24 and on days 1-5 of weeks 3, 9, 15, and 21; doxorubicin hydrochloride IV (beginning after CTX infusion) weekly on weeks 0, 6, 12, 18, and 24; and etoposide (VP-16) IV over 1 hour (beginning after CTX infusion) on days 1-5 of weeks 3, 9, 15, and 21. Filgrastim (G-CSF) is administered subcutaneously (SC) beginning 24 hours after completion of chemotherapy and continuing until blood counts recover. Patients also undergo abdominal radiotherapy and whole lung radiotherapy (if pulmonary metastases are present).

Active Comparator: Stratum 9 - Stages I-IV rhabdoid tumor: After conventional surgery (nephrectomy), patients receive carboplatin IV on days 1-2 and VP-16 IV over 1 hour (beginning after carboplatin infusion) on days 1-3 of weeks 0, 3, 9, 12, 18, and 21 and CTX IV over 1 hour on days 1-5 of weeks 6, 15, and 24. Filgrastim G-CSF is administered as on stratum 7. Patients also undergo radiation therapy. After completion of chemotherapy, patients undergo second-look conventional surgery (laparotomy) and conventional surgery (partial nephrectomy or wedge excision if feasible). After conventional surgery (second-look surgery), patients without persistent or residual disease resume chemotherapy.


Other interventions: dactinomycin


Other interventions: filgrastim


Treatment: Drugs: cyclophosphamide


Treatment: Drugs: doxorubicin hydrochloride
Source and Pharmacology: An anthracycline antibiotic isolated from cultures of Streptomyces peucetius. Binds to DNA and inhibits nucleic acid synthesis, with its major lethal effect occurring during the S phase of the cell cycle. Has some topoisomerase II inhibitory activity. Since it is primarily excreted by the liver, any liver impairment may enhance toxicity. 40% to 50% is excreted in the bile; <5% in the urine. The drug has a very short initial t½ of <20 minutes and a terminal t½ of 17 hours. Animal studies indicate cytotoxic levels persist in tissue for as long as 24 hours.

Treatment: Drugs: etoposide


Treatment: Drugs: vincristine sulfate


Treatment: Surgery: conventional surgery


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

Outcomes
Primary outcome [1] 0 0
Progression free survival
Timepoint [1] 0 0

Eligibility
Key inclusion criteria
DISEASE CHARACTERISTICS:

- Histologically confirmed stage I-V kidney cancer of one of the following histologies:

- Wilms' tumor, favorable histology

- Wilms' tumor, focal or diffuse anaplastic

- Clear cell sarcoma

- Rhabdoid tumor

- (The rhabdoid tumor stratum closed to accrual effective 07/13/2001)

- Prior nephrectomy or biopsy required

- Prior bilateral biopsy (preferably open) with bilateral staging and pathologic
evaluation required for bilateral tumor

- Must begin study therapy within 5 days after nephrectomy (unless medically
contraindicated)

PATIENT CHARACTERISTICS:

Age:

- Under 16

Performance status:

- Not specified

Life expectancy:

- Not specified

Hematopoietic:

- Not specified

Hepatic:

- Not specified

Renal:

- Not specified

Other:

- Not pregnant

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Not specified

Chemotherapy:

- No prior chemotherapy

Endocrine therapy:

- Not specified

Radiotherapy:

- No prior radiotherapy

Surgery:

- See Disease Characteristics
Minimum age
0 Years
Maximum age
15 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
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
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
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
1/07/1995
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2003
Sample size
Target
Accrual to date
Final
3031
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
Children's Hospital at Westmead - Westmead
Recruitment hospital [3] 0 0
Royal Children's Hospital - Brisbane
Recruitment hospital [4] 0 0
Women's and Children's Hospital - North Adelaide
Recruitment hospital [5] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [6] 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 - Brisbane
Recruitment postcode(s) [4] 0 0
5006 - North Adelaide
Recruitment postcode(s) [5] 0 0
3052 - Parkville
Recruitment postcode(s) [6] 0 0
6001 - Perth
Recruitment outside Australia
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Alabama
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Arizona
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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
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
they stop growing or die. Radiation therapy uses high energy x-rays to damage tumor cells. It
is not yet known whether combination chemotherapy alone or combination chemotherapy plus
radiation therapy is more effective for childhood kidney cancer.

PURPOSE: Phase III trial to compare the effectiveness of combination chemotherapy with or
without radiation therapy in treating children who have kidney cancer.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00002611
Trial related presentations / publications
Grundy PE, Green DM, Dirks AC, Berendt AE, Breslow NE, Anderson JR, Dome JS. Clinical significance of pulmonary nodules detected by CT and Not CXR in patients treated for favorable histology Wilms tumor on national Wilms tumor studies-4 and -5: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2012 Oct;59(4):631-5. doi: 10.1002/pbc.24123. Epub 2012 Mar 15.
Kieran K, Anderson JR, Dome JS, Ehrlich PF, Ritchey ML, Shamberger RC, Perlman EJ, Green DM, Davidoff AM. Lymph node involvement in Wilms tumor: results from National Wilms Tumor Studies 4 and 5. J Pediatr Surg. 2012 Apr;47(4):700-6. doi: 10.1016/j.jpedsurg.2011.08.017.
Lange J, Peterson SM, Takashima JR, Grigoriev Y, Ritchey ML, Shamberger RC, Beckwith JB, Perlman E, Green DM, Breslow NE. Risk factors for end stage renal disease in non-WT1-syndromic Wilms tumor. J Urol. 2011 Aug;186(2):378-86. doi: 10.1016/j.juro.2011.03.110. Epub 2011 Jun 17.
Kalapurakal JA, Green DM, Haase G, Anderson JR, Dome JS, Grundy PE. Outcomes of children with favorable histology wilms tumor and peritoneal implants treated in National Wilms Tumor Studies-4 and -5. Int J Radiat Oncol Biol Phys. 2010 Jun 1;77(2):554-8. doi: 10.1016/j.ijrobp.2009.04.081.
Ehrlich PF, Ferrer FA, Ritchey ML, Anderson JR, Green DM, Grundy PE, Dome JS, Kalapurakal JA, Perlman EJ, Shamberger RC. Hepatic metastasis at diagnosis in patients with Wilms tumor is not an independent adverse prognostic factor for stage IV Wilms tumor: a report from the Children's Oncology Group/National Wilms Tumor Study Group. Ann Surg. 2009 Oct;250(4):642-8. doi: 10.1097/SLA.0b013e3181b76f20.
Ritchey M, Daley S, Shamberger RC, Ehrlich P, Hamilton T, Haase G, Sawin R; National Wilms' Tumor Study Group. Ureteral extension in Wilms' tumor: a report from the National Wilms' Tumor Study Group (NWTSG). J Pediatr Surg. 2008 Sep;43(9):1625-9. doi: 10.1016/j.jpedsurg.2008.01.067.
van den Heuvel-Eibrink MM, Grundy P, Graf N, Pritchard-Jones K, Bergeron C, Patte C, van Tinteren H, Rey A, Langford C, Anderson JR, de Kraker J. Characteristics and survival of 750 children diagnosed with a renal tumor in the first seven months of life: A collaborative study by the SIOP/GPOH/SFOP, NWTSG, and UKCCSG Wilms tumor study groups. Pediatr Blood Cancer. 2008 Jun;50(6):1130-4. doi: 10.1002/pbc.21389.
Breslow NE, Beckwith JB, Perlman EJ, Reeve AE. Age distributions, birth weights, nephrogenic rests, and heterogeneity in the pathogenesis of Wilms tumor. Pediatr Blood Cancer. 2006 Sep;47(3):260-7. doi: 10.1002/pbc.20891.
Kalapurakal JA, Nan B, Norkool P, Coppes M, Perlman E, Beckwith B, Ritchey M, Breslow N, Grundy P, D'angio GJ, Green DM, Thomas PR. Treatment outcomes in adults with favorable histologic type Wilms tumor-an update from the National Wilms Tumor Study Group. Int J Radiat Oncol Biol Phys. 2004 Dec 1;60(5):1379-84. doi: 10.1016/j.ijrobp.2004.05.057.
Public notes

Contacts
Principal investigator
Name 0 0
Daniel M. Green, MD
Address 0 0
Roswell Park Cancer Institute
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/ct2/show/NCT00002611