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Combination Chemotherapy Alone or With Radiation Therapy in Treating Children With Kidney Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00002611
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : July 24, 2014
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Tracking Information
First Submitted Date  ICMJE November 1, 1999
First Posted Date  ICMJE January 27, 2003
Last Update Posted Date July 24, 2014
Study Start Date  ICMJE July 1995
Actual Primary Completion Date June 2002   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 23, 2014)
Progression free survival
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combination Chemotherapy Alone or With Radiation Therapy in Treating Children With Kidney Cancer
Official Title  ICMJE NATIONAL WILMS TUMOR STUDY-5 -- THERAPEUTIC TRIAL AND BIOLOGY STUDY
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.

Detailed Description

OBJECTIVES:

  • Increase survival rate of children with favorable histology (FH) Wilms' tumor and other childhood renal tumors.
  • Determine whether loss of heterozygosity for chromosome 16q or 1p in tumor tissue is associated with a poorer prognosis in children with FH Wilms' tumor.
  • Determine whether increased DNA content in tumor cells is associated with a poorer prognosis in children with FH Wilms' tumor.
  • Decrease the acute and long-term morbidity in children with Wilms' tumor by limiting initial therapy and consistently using the same regimen (protocol NWTS-5/R) for patients who relapse following initial treatment.
  • Improve overall and disease-free survival of patients with renal tumors of unfavorable histology, including Wilms' tumor with diffuse anaplasia and clear cell sarcoma of the kidney, using a new treatment regimen that includes etoposide (VP-16) and cyclophosphamide (CTX).
  • Improve overall and disease-free survival in patients with malignant rhabdoid tumor of the kidney using a new treatment regimen that includes carboplatin, VP-16, and CTX. (The rhabdoid tumor stratum closed to accrual effective 07/13/2001)
  • Provide data regarding loss of heterozygosity for chromosomes 11p15, 16q, and 1p, age at diagnosis, precursor lesions (perilobar, intralobar, nephroblastomatosis), bilaterality, and presence of congenital anomalies required for the completion of protocol A0026 (a case-control study of risk factors for Wilms' tumor).

OUTLINE: This is a multicenter study. Patients are assigned to one of nine strata based on tumor histology, stage, tumor weight, and age.

  • Stratum 1 (stage I favorable histology (FH) Wilms' tumor, under 24 months of age, and tumor weight less than 550 g): After nephrectomy, patients receive regimen EE-4A comprising dactinomycin (DACT) IV weekly on weeks 0, 3, 6, 9, 12, 15, and 18 and vincristine (VCR) IV weekly on weeks 1-10, 12, 15, and 18.
  • 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 therapy as in stratum 1.
  • Stratum 3 (stage II FH Wilms' tumor): Patients receive therapy as in stratum 1.
  • Stratum 4 (stage III FH Wilms' tumor; stage II or III FA Wilms' tumor): After nephrectomy, patients receive regimen DD-4A comprising DACT IV weekly on weeks 0, 6, 12, 18, and 24; doxorubicin IV weekly on weeks 3, 9, 15, and 21; and VCR IV weekly on weeks 1-10, 12, 15, 18, 21, and 24. Patients also undergo abdominal radiotherapy.
  • Stratum 5 (stage IV FH or FA Wilms' tumor): Patients receive chemotherapy as in stratum 4, abdominal radiotherapy, and whole lung radiotherapy (at the discretion of the investigator).
  • Stratum 6 (stage V FH, FA, or DA Wilms' tumor ): After bilateral biopsy, patients with FH receive chemotherapy as in stratum 1 or 4. Patients with FA or DA receive chemotherapy as in stratum 7.
  • Stratum 7 (stages I-IV clear cell sarcoma): After nephrectomy, patients receive VCR IV weekly on weeks 1, 2, 4-8, 10-13, 18, and 24; cyclophosphamide (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 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).
  • Stratum 8 (stages II-IV DA Wilms' tumor): Patients receive treatment as in stratum 7.
  • Stratum 9 (stages I-IV rhabdoid tumor): After 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. G-CSF is administered as in stratum 7. Patients also undergo radiotherapy. (The rhabdoid tumor stratum closed to accrual effective 07/13/2001.) After completion of chemotherapy, patients undergo second-look laparotomy and partial nephrectomy or wedge excision (if feasible). After second-look surgery, patients without persistent or residual disease resume chemotherapy.

Patients are followed every 3 months for 5 years, every 6 months for 2 years, and then annually for 3 years.

PROJECTED ACCRUAL: A total of 207 patients will be accrued for the treatment portion of this study. (The rhabdoid tumor stratum closed to accrual effective 07/13/2001.)

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Primary Purpose: Treatment
Condition  ICMJE Kidney Cancer
Intervention  ICMJE
  • Biological: dactinomycin
  • Biological: filgrastim
  • Drug: cyclophosphamide
  • Drug: 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.
    Other Names:
    • NSC #123127
    • (Adriamycin)
  • Drug: etoposide
  • Drug: vincristine sulfate
  • Procedure: conventional surgery
  • Radiation: radiation therapy
Study Arms  ICMJE
  • 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.
    Interventions:
    • Biological: dactinomycin
    • Drug: vincristine sulfate
    • Procedure: conventional surgery
  • 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.
    Interventions:
    • Biological: dactinomycin
    • Drug: vincristine sulfate
  • 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.
    Interventions:
    • Biological: dactinomycin
    • Drug: vincristine sulfate
  • 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.
    Interventions:
    • Biological: dactinomycin
    • Drug: doxorubicin hydrochloride
    • Drug: vincristine sulfate
    • Procedure: conventional surgery
    • Radiation: 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).
    Interventions:
    • Biological: dactinomycin
    • Drug: doxorubicin hydrochloride
    • Drug: vincristine sulfate
  • 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.
    Interventions:
    • Biological: dactinomycin
    • Biological: filgrastim
    • Drug: cyclophosphamide
    • Drug: doxorubicin hydrochloride
    • Drug: etoposide
    • Drug: vincristine sulfate
    • Procedure: conventional surgery
  • 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).
    Interventions:
    • Biological: filgrastim
    • Drug: doxorubicin hydrochloride
    • Drug: etoposide
    • Procedure: conventional surgery
    • Radiation: radiation therapy
  • 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).
    Interventions:
    • Biological: filgrastim
    • Drug: cyclophosphamide
    • Drug: doxorubicin hydrochloride
    • Drug: etoposide
    • Drug: vincristine sulfate
    • Procedure: conventional surgery
    • Radiation: radiation therapy
  • 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.
    Interventions:
    • Biological: filgrastim
    • Drug: etoposide
    • Procedure: conventional surgery
    • Radiation: radiation therapy
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 23, 2014)
3031
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE August 2003
Actual Primary Completion Date June 2002   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 15 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   Netherlands,   New Zealand,   Puerto Rico,   Switzerland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00002611
Other Study ID Numbers  ICMJE 9440
COG-Q9401 ( Other Identifier: Children's Oncology Group )
NWTS-Q9401 ( Other Identifier: NWTS )
CCG-4941 ( Other Identifier: Children's Cancer Group )
POG-9440 ( Other Identifier: Pediatric Oncology Group )
INT-0150
NWTS-5 ( Other Identifier: NWTS )
CDR0000063901 ( Other Identifier: NCI )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Children's Oncology Group
Study Sponsor  ICMJE Children's Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Daniel M. Green, MD Roswell Park Cancer Institute
PRS Account Children's Oncology Group
Verification Date July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP