Chemotherapy With or Without Surgery, Radiation Therapy, or Stem Cell Transplantation in Treating Young Patients With Kidney Tumors

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00002610
First received: November 1, 1999
Last updated: July 23, 2014
Last verified: July 2014

November 1, 1999
July 23, 2014
January 1996
June 2002   (final data collection date for primary outcome measure)
Event free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
To determine the two-year second event-free survival percentage for children who relapse following initial therapy with nephrectomy only following treatment with vincristine and dactinomycin, with or without doxorubicin, depending upon the site of relapse and presence or absence of microscopic residual disease.
Not Provided
Complete list of historical versions of study NCT00002610 on ClinicalTrials.gov Archive Site
  • Event Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine if the two-year second event-free survival percentage for children who relapse following initial treatment with Regimen EE-4A who do not have loss of heterozygosity of markers for chromosome 16q, 1p or increased DNA content in tumor cells is not less than 40% higher than that of similar patients who have loss of heterozygosity for chromosome 16q, 1p or increased DNA content following treatment with intensive chemotherapy using doxorubicin, etoposide, cyclophosphamide and carboplatin, and radiation therapy to sites of microscopic or gross residual disease.
  • Post-relapse survival [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    To determine if the four-year post-relapse survival percentage for children who relapse following initial treatment with Regimen DD - 4A who do not have loss of heterozygosity of markers for chromosome 16q, 1p or increased DNA content in tumor cells is not less than 40% higher than that of similar patients who have loss of heterozygosity for chromosome 16q, 1p or increased DNA content following treatment with intensive chemotherapy using etoposide, cyclophosphamide and carboplatin.
  • Response rate [ Designated as safety issue: No ]
    To determine if the response rate (CR + PR) of clear cell sarcoma of the kidney and diffuse anaplastic Wilms tumor to the combination of carboplatin and etoposide each exceed 20%.
Not Provided
Not Provided
Not Provided
 
Chemotherapy With or Without Surgery, Radiation Therapy, or Stem Cell Transplantation in Treating Young Patients With Kidney Tumors
National Wilms Tumor Study-5 -- Treatment of Relapsed Patients, A National Wilms Tumor Study Group Phase III Study

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. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. It is not yet known which therapy regimen is most effective for treating patients with kidney tumors.

PURPOSE: Phase III trial to compare the effectiveness of chemotherapy with or without radiation therapy, surgery, and/or peripheral stem cell or bone marrow transplantation in treating young patients with kidney tumors.

OBJECTIVES:

  • Determine the 2-year second-event-free survival after vincristine (VCR) and dactinomycin (DACT) with or without doxorubicin (DOX), depending on the site of relapse and presence of microscopic residual disease, in children with relapsed Wilm's tumor previously treated with nephrectomy alone as initial therapy.
  • Determine whether the 2-year second-event-free survival after intensive doxorubicin, etoposide (VP-16), cyclophosphamide (CTX), and carboplatin (CBDCA) plus radiotherapy to residual disease is at least 40% higher in patients with relapsed Wilm's tumor previously treated with Regimen EE-4A as initial therapy and without loss of heterozygosity for chromosomes 16q and 1p and increased DNA content in tumor cells than for similarly treated patients with loss of heterozygosity for chromosome 16q or 1p or increased DNA content in tumor cells.
  • Determine whether the 4-year post-relapse survival after intensive VP-16, CTX, and CBDCA is at least 40% higher in patients with relapsed Wilm's tumor previously treated with Regimen DD-4A as initial therapy and without loss of heterozygosity for chromosomes 16q and 1p and increased DNA content in tumor cells than for similarly treated patients with loss of heterozygosity for chromosome 16q or 1p or increased DNA content in tumor cells.
  • Determine whether the rates of complete and partial response exceed 20% in patients with relapsed clear cell sarcoma of the kidney or diffuse anaplastic Wilms' tumor treated with CBDCA combined with VP-16.

OUTLINE: This is a multicenter study.

Patients are assigned to a treatment group based on initial therapy and histology. Patients under age 2 at diagnosis who were previously treated with nephrectomy as initial therapy for stage I favorable histology Wilms' tumor weighing less than 550 grams are assigned to group A. Patients who received Regimen EE-4A as initial therapy for Wilms' tumor are assigned to group B. Patients who received Regimen DD-4A as initial therapy for Wilms' tumor are assigned to group C. Patients with clear cell sarcoma of the kidney or diffuse anaplastic Wilms' tumor are assigned to group D.

Group A

  • Treatment is determined by site of relapse and the presence of microscopic or gross residual disease after attempted resection of relapsed disease. Children with suspected intra-abdominal recurrence undergo exploratory surgery to determine the site of recurrence and to obtain tissue for microscopic examination. Patients with stage I disease after recurrence are treated with regimen EE-4A. Patients with stage II or III disease are treated with regimen DD-4A.

    • Regimen EE-4A: Patients receive dactinomycin (DACT) IV on weeks 0, 3, 6, 9, 12, 15, and 18 and vincristine (VCR) IV on weeks 1-10, 12, 15, and 18 in the absence of disease progression.
    • Regimen DD-4A: Patients receive DACT IV on weeks 0, 6, 12, 18, and 24; VCR IV weekly on weeks 1-10, 12, 15, 18, 21, and 24; doxorubicin (DOX) IV on weeks 3, 9, 15, and 21; and abdominal radiotherapy in the absence of disease progression.

Group B

  • Patients undergo resection. After resection, patients receive regimen I comprising DOX IV on weeks 0, 6, 12, 18, and 24; VCR IV on weeks 1, 2, 4, 5-8, 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; and etoposide (VP-16) IV over 1 hour (after CTX infusion) on days 1-5 of weeks 3, 9, 15, and 21 in the absence of disease progression. Filgrastim (G-CSF) is administered subcutaneously (SC) beginning 24 hours after completion of chemotherapy and continuing until blood counts recover. Patients undergo radiotherapy to site of recurrence beginning within 1 week after initiation of chemotherapy.

Group C

  • Induction: Patients receive CTX IV over 1 hour on days 1-5 of weeks 0 and 3; VP-16 IV over 1 hour (after CTX infusion) on days 1-5 of weeks of 0 and 3 and on days 1-3 of weeks 6 and 9; and carboplatin (CBDCA) IV over 6 hours on days 1 and 2 of weeks 6 and 9 in the absence of disease progression. G-CSF is administered SC beginning 24 hours after completion of CTX/VP-16 or CBDCA/VP-16 and continuing until blood counts recover.
  • Surgery: Patients with detectable disease undergo resection on week 13. If complete resection is not achieved or if it is deemed impossible, resection must be attempted no later than 3 weeks after consolidation radiotherapy.
  • Consolidation: Beginning within 9 days of surgery, patients receive CTX IV over 1 hour on days 1-5 of week 1; VP-16 IV over 1 hour (after CTX infusion) on days 1-5 of week 1 and on days 1-3 of week 4; CBDCA IV over 6 hours on days 1 and 2 of week 4; G-CSF as in induction; and radiotherapy in the absence of disease progression. Patients with complete or partial response after resection and/or radiotherapy proceed to maintenance therapy.
  • Maintenance: Patients receive CTX IV over 1 hour on days 1-5 of weeks 0 and 3; VP-16 IV over 1 hour on days 1-5 of weeks 0 and 3 and on days 1-3 of weeks 6 and 9; CBDCA IV over 6 hours on days 1 and 2 of weeks 6 and 9; and G-CSF as in induction. Treatment continues every 12 weeks for 6 courses in the absence of disease progression.

Group D

  • Patients receive CBDCA IV over 6 hours on days 1 and 2 and VP-16 IV over 1 hour (after CBDCA infusion) on days 1-3 of weeks 0 and 3. Treatment continues weekly for 6 courses in the absence of disease progression.

Patients are followed every 3 months for 15 months, every 6 months for 1 year, and then annually for 3 years.

PROJECTED ACCRUAL: Not specified

Interventional
Phase 3
Allocation: Non-Randomized
Primary Purpose: Treatment
Kidney Cancer
  • Biological: dactinomycin
    Other Names:
    • Actinomycin-D
    • Cosmegen
    • NSC #3053
  • Biological: filgrastim
    Other Names:
    • Granulocyte-colony stimulating factor
    • r-MetHuG-CSF
    • GCSF
    • Neupogen
    • NSC #614629
  • Drug: carboplatin
    Other Names:
    • CBDCA
    • NSC #241240
  • Drug: cyclophosphamide
    Other Names:
    • CTX
    • Cytoxan
    • NSC #2626-71
  • Drug: doxorubicin hydrochloride
    Other Names:
    • Adriamycin
    • NSC #123127
  • Drug: etoposide
    Other Names:
    • VP-16
    • VePesid
    • NSC #141540
  • Drug: vincristine sulfate
    IV
    Other Name: VCR
  • Procedure: conventional surgery
  • Radiation: radiation therapy
  • Experimental: STRATUM A
    Treatment of children in Stratum A will be determined by the site of relapse and the presence of microscopic or gross residual disease after attempted surgical excision of the relapse.
    Interventions:
    • Biological: dactinomycin
    • Drug: doxorubicin hydrochloride
    • Drug: vincristine sulfate
    • Procedure: conventional surgery
    • Radiation: radiation therapy
  • Experimental: Stratum B
    All children who received combination chemotherapy with Regimen EE - 4A as their initial therapy for Wilms tumor will receive Regimen I and radiation therapy to the site of recurrence. All patients will receive prophylactic trimethoprim /sulfamethoxazole
    Interventions:
    • Biological: filgrastim
    • Drug: cyclophosphamide
    • Drug: doxorubicin hydrochloride
    • Drug: etoposide
    • Drug: vincristine sulfate
    • Procedure: conventional surgery
    • Radiation: radiation therapy
  • Experimental: STRATUM C
    All children who received combination chemotherapy with Regimen DD - 4A as their initial therapy for Wilms tumor will be treated with the following chemotherapy. All patients will receive prophylactic trimethoprim/sulfamethoxazole
    Interventions:
    • Biological: filgrastim
    • Drug: carboplatin
    • Drug: cyclophosphamide
    • Drug: etoposide
    • Procedure: conventional surgery
    • Radiation: radiation therapy
  • Experimental: STRATUM D
    Six week cycles of chemotherapy will be given to all patients who do not have progressive disease at the time of each week 0 re-evaluation.
    Interventions:
    • Drug: carboplatin
    • Drug: etoposide

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
203
February 2006
June 2002   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Diagnosis of Wilms' tumor

    • Eligible subtypes:

      • Favorable histologies
      • Anaplastic histologies
      • Clear cell sarcoma of the kidney
      • Rhabdoid tumor of the kidney
  • Relapsed disease after entry on protocol NWTS-5 (NWTS-Q9401)

PATIENT CHARACTERISTICS:

Age:

  • 21 and under at original diagnosis

Performance status:

  • Not specified

Life expectancy:

  • At least 4 weeks

Hematopoietic:

  • Absolute neutrophil count at least 1,000/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic:

  • Bilirubin no greater than 1.5 times normal
  • SGOT or SGPT less than 2.5 times normal

Renal:

  • Creatinine no greater than 1.5 times normal OR
  • Creatinine clearance or GFR at least 70 mL/min

Cardiovascular:

  • Shortening fraction at least 27% by echocardiogram OR
  • Ejection fraction greater than 50% by echocardiogram or MUGA scan

Other:

  • Not pregnant
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • At least 2 weeks since prior chemotherapy and recovered

Endocrine therapy

  • Not specified

Radiotherapy

  • Not specified

Surgery

  • Not specified

Other

  • No prior therapy for relapsed Wilms' tumor
  • Recovered from the toxic effects of any other prior therapy
Both
up to 21 Years
No
Contact information is only displayed when the study is recruiting subjects
Netherlands,   United States,   Canada,   Australia,   Puerto Rico,   New Zealand,   Switzerland
 
NCT00002610
9444, COG-Q9402, NWTS-Q9402, CCG-4942, POG-9444, INT-0152, NWTS-5/R, CDR0000063900
Yes
Children's Oncology Group
Children's Oncology Group
National Cancer Institute (NCI)
Study Chair: Daniel M. Green, MD Roswell Park Cancer Institute
Children's Oncology Group
July 2014

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