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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00002611
First received: November 1, 1999
Last updated: July 23, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Kidney Cancer
Biological: dactinomycin
Biological: filgrastim
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: vincristine sulfate
Procedure: conventional surgery
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: NATIONAL WILMS TUMOR STUDY-5 -- THERAPEUTIC TRIAL AND BIOLOGY STUDY

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Progression free survival [ Designated as safety issue: No ]

Enrollment: 3031
Study Start Date: July 1995
Study Completion Date: August 2003
Primary Completion Date: June 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
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.
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.
Biological: dactinomycin 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: 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).
Biological: dactinomycin 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: 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.
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
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).
Biological: filgrastim 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 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).
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
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.
Biological: filgrastim Drug: etoposide Procedure: conventional surgery Radiation: radiation therapy

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 15 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002611

  Show 235 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Daniel M. Green, MD Roswell Park Cancer Institute
  More Information

Additional Information:
Publications:
Seibel NL, Sun J, Anderson JR, et al.: Outcome of clear cell sarcoma of the kidney (CCSK) treated on the National Wilms Tumor Study-5 (NWTS). [Abstract] J Clin Oncol 24 (Suppl 18): A-9000, 502s, 2006.

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00002611     History of Changes
Other Study ID Numbers: 9440, COG-Q9401, NWTS-Q9401, CCG-4941, POG-9440, INT-0150, NWTS-5, CDR0000063901
Study First Received: November 1, 1999
Last Updated: July 23, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
stage I Wilms tumor
stage II Wilms tumor
stage III Wilms tumor
stage IV Wilms tumor
stage V Wilms tumor
clear cell sarcoma of the kidney

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Neoplasms
Adenocarcinoma
Carcinoma
Kidney Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Cyclophosphamide
Dactinomycin
Doxorubicin
Etoposide
Etoposide phosphate
Lenograstim
Liposomal doxorubicin
Vincristine
Adjuvants, Immunologic
Alkylating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antirheumatic Agents

ClinicalTrials.gov processed this record on October 21, 2014