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
  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. 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.


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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Primary Purpose: Treatment
Official Title: National Wilms Tumor Study-5 -- Treatment of Relapsed Patients, A National Wilms Tumor Study Group Phase III Study

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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%.


Enrollment: 203
Study Start Date: January 1996
Study Completion Date: February 2006
Primary Completion Date: June 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: dactinomycin
Other Names:
  • Actinomycin-D
  • Cosmegen
  • NSC #3053
Drug: doxorubicin hydrochloride
Other Names:
  • Adriamycin
  • NSC #123127
Drug: vincristine sulfate
IV
Other Name: VCR
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
Biological: filgrastim
Other Names:
  • Granulocyte-colony stimulating factor
  • r-MetHuG-CSF
  • GCSF
  • Neupogen
  • NSC #614629
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 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
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: etoposide
Other Names:
  • VP-16
  • VePesid
  • NSC #141540
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.
Drug: carboplatin
Other Names:
  • CBDCA
  • NSC #241240
Drug: etoposide
Other Names:
  • VP-16
  • VePesid
  • NSC #141540

  Hide Detailed Description

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00002610

  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:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00002610     History of Changes
Other Study ID Numbers: 9444, COG-Q9402, NWTS-Q9402, CCG-4942, POG-9444, INT-0152, NWTS-5/R, CDR0000063900
Study First Received: November 1, 1999
Last Updated: July 23, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
recurrent Wilms tumor and other childhood kidney tumors
clear cell sarcoma of the kidney
rhabdoid tumor of the kidney

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Neoplasms
Wilms Tumor
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Neoplasms, Complex and Mixed
Neoplastic Syndromes, Hereditary
Genetic Diseases, Inborn
Dactinomycin
Doxorubicin
Cyclophosphamide
Etoposide
Vincristine
Carboplatin
Lenograstim
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 29, 2014