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.

Study Overview

• Status: Completed
• Conditions: Kidney Cancer
• Intervention / Treatment: Drug: carboplatin; Drug: cyclophosphamide; Radiation: radiation therapy; Drug: etoposide; Drug: doxorubicin hydrochloride; Procedure: conventional surgery; Biological: filgrastim; Biological: dactinomycin; Drug: vincristine sulfate

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

• Study Type: Interventional
• Enrollment (Actual): 203
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Sydney Children's Hospital
    • Westmead, New South Wales, Australia, 2145
      • Children's Hospital at Westmead
  • Queensland
    • Brisbane, Queensland, Australia, 4029
      • Royal Children's Hospital
  • South Australia
    • North Adelaide, South Australia, Australia, 5006
      • Women's and Children's Hospital
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Royal Children's Hospital
  • Western Australia
    • Perth, Western Australia, Australia, 6001
      • Princess Margaret Hospital for Children
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2T 5C7
      • Alberta Children's Hospital
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • British Columbia Children's Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Janeway Children's Health and Rehabilitation Centre
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3J 3G9
      • IWK Health Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Children's Hospital
    • London, Ontario, Canada, N6C 2V5
      • Children's Hospital of Western Ontario
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Hospital for Sick Children
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • Hopital Sainte Justine
    • Montreal, Quebec, Canada, H3H 1P3
      • McGill University Health Center - Montreal Children's Hospital
    • Sainte Foy, Quebec, Canada, GIV 4G2
      • Centre Hospitalier de l'Universite Laval
    • Sainte-Foy, Quebec, Canada, G1V 4G2
      • Laval University Medical Center
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre
• Netherlands
  • Groningen, Netherlands, 9700 RB
    • Academisch Ziekenhuis Groningen
• New Zealand
  • Auckland, New Zealand
    • Starship Children's Hospital
• Puerto Rico
  • San Juan, Puerto Rico, 00936-5067
    • University of Puerto Rico School of Medicine Medical Sciences Campus
  • Santurce, Puerto Rico, 00912
    • San Jorge Childrens Hospital
• Switzerland
  • Bern, Switzerland, CH 3010
    • Swiss Pediatric Oncology Group Bern
  • Geneva, Switzerland, CH 1211
    • Swiss Pediatric Oncology Group Geneva
  • Lausanne, Switzerland, CH 1011
    • Swiss Pediatric Oncology Group Lausanne
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham Comprehensive Cancer Center
    • Mobile, Alabama, United States, 36604
      • University of South Alabama Medical Center
  • Arizona
    • Phoenix, Arizona, United States, 85016-7710
      • Phoenix Children's Hospital
    • Tucson, Arizona, United States, 85724
      • Arizona Cancer Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Downey, California, United States, 90242
      • Southern California Permanente Medical Group
    • Duarte, California, United States, 91010-3000
      • City of Hope Comprehensive Cancer Center
    • La Jolla, California, United States, 92093-0658
      • Rebecca and John Moores UCSD Cancer Center
    • Loma Linda, California, United States, 92354
      • Loma Linda University Medical Center
    • Long Beach, California, United States, 90801-1428
      • Jonathan Jaques Children'S Cancer Center
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center, UCLA
    • Los Angeles, California, United States, 90027-0700
      • Children's Hospital Los Angeles
    • Madera, California, United States, 93638-8762
      • Children's Hospital Central California
    • Oakland, California, United States, 94609-1809
      • Children's Hospital of Oakland
    • Orange, California, United States, 92868
      • Chao Family Comprehensive Cancer Center
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
    • Palo Alto, California, United States, 94304
      • Lucile Packard Children's Hospital at Stanford
    • Sacramento, California, United States, 95816
      • Sutter Cancer Center
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
    • San Diego, California, United States, 92120
      • Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego
    • San Diego, California, United States, 92123-4282
      • Children's Hospital San Diego
    • San Francisco, California, United States, 94115
      • Kaiser Permanente Medical Center - San Francisco Geary Campus
    • San Francisco, California, United States, 94143-0128
      • UCSF Comprehensive Cancer Center
    • Santa Barbara, California, United States, 93102
      • Santa Barbara Cottage Hospital
    • Santa Clara, California, United States, 95051-5386
      • Kaiser Permanente Medical Center - Santa Clara
    • Travis Air Force Base, California, United States, 94535
      • David Grant Medical Center
  • Colorado
    • Denver, Colorado, United States, 80218-1088
      • Children's Hospital of Denver
    • Denver, Colorado, United States, 80218
      • Childhood Hematology/Oncology Associates
    • Denver, Colorado, United States, 80218
      • Presbyterian-St Luke's Medical Center
  • Connecticut
    • Farmington, Connecticut, United States, 06360-7106
      • University of Connecticut Health Center
    • New Haven, Connecticut, United States, 06520-8028
      • Yale Comprehensive Cancer Center
  • Delaware
    • Wilmington, Delaware, United States, 19899
      • Alfred I. Dupont Institute
  • District of Columbia
    • Washington, District of Columbia, United States, 20307-5000
      • Walter Reed Army Medical Center
    • Washington, District of Columbia, United States, 20010-2970
      • Children's National Medical Center
    • Washington, District of Columbia, United States, 20007
      • Lombardi Cancer Center
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Broward General Medical Center
    • Fort Myers, Florida, United States, 33908
      • Children's Hospital of Southwest Florida
    • Gainesville, Florida, United States, 32610-100277
      • Shands Hospital and Clinics, University of Florida
    • Hollywood, Florida, United States, 33021
      • Joe DiMaggio Children's Hospital at Memorial
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic
    • Miami, Florida, United States, 33176-2197
      • Baptist Hospital of Miami
    • Miami, Florida, United States, 33136
      • University of Miami-Jackson Memorial Hospital
    • Miami, Florida, United States, 33155-4069
      • Miami Children's Hospital
    • Orlando, Florida, United States, 32803
      • Florida Hospital Cancer Institute
    • Orlando, Florida, United States, 32806
      • Nemours Children's Clinic-Orlando
    • Pensacola, Florida, United States, 32504
      • Sacred Heart Children's Hospital
    • St. Petersburg, Florida, United States, 33701
      • All Children's Hospital
    • Tampa, Florida, United States, 33677-4227
      • Tampa Children's Hospital
    • West Palm Beach, Florida, United States, 33407
      • St. Mary's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital - Atlanta
    • Atlanta, Georgia, United States, 30342
      • Children's Healthcare of Atlanta - Scottish Rite
    • Augusta, Georgia, United States, 30912-4000
      • Medical College of Georgia Comprehensive Cancer Center
    • Macon, Georgia, United States, 31201
      • Medical Center of Central Georgia
    • Savannah, Georgia, United States, 31403-3089
      • Memorial Health University Medical Center, Inc.
  • Hawaii
    • Honolulu, Hawaii, United States, 96859-5000
      • Tripler Army Medical Center
    • Honolulu, Hawaii, United States, 96813
      • Cancer Research Center of Hawaii
    • Honolulu, Hawaii, United States, 96813
      • MBCCOP - Hawaii
  • Idaho
    • Boise, Idaho, United States, 83712
      • Mountain States Tumor Institute
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
    • Chicago, Illinois, United States, 60612
      • Rush-Presbyterian-St. Luke's Medical Center
    • Chicago, Illinois, United States, 60614
      • Children's Memorial Hospital - Chicago
    • Chicago, Illinois, United States, 60601
      • University of Chicago Cancer Research Center
    • Oak Lawn, Illinois, United States, 60453
      • Hope Children's Hospital
    • Park Ridge, Illinois, United States, 60068-1174
      • Lutheran General Hospital
    • Peoria, Illinois, United States, 61637
      • Saint Jude Midwest Affiliate
    • Springfield, Illinois, United States, 62794-9658
      • Southern Illinois University School of Medicine
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5289
      • Indiana University Cancer Center
    • Indianapolis, Indiana, United States, 46260
      • St. Vincent Hospital and Health Care Center
  • Iowa
    • Des Moines, Iowa, United States, 50308
      • Raymond Blank Memorial Hospital for Children
    • Des Moines, Iowa, United States, 50309
      • John Stoddard Cancer Center
    • Iowa City, Iowa, United States, 52242-1009
      • Holden Comprehensive Cancer Center
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Wesley Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0284
      • Albert B. Chandler Medical Center, University of Kentucky
    • Louisville, Kentucky, United States, 40202-3830
      • Kosair Children's Hospital
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University School of Medicine
    • New Orleans, Louisiana, United States, 70118
      • Children's Hospital of New Orleans
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic
  • Maine
    • Bangor, Maine, United States, 04401
      • Eastern Maine Medical Center
    • Scarborough, Maine, United States, 04074
      • Maine Children's Cancer Program
  • Maryland
    • Baltimore, Maryland, United States, 21231-2410
      • Sidney kimmel comprehensive cancer center at johns hopkins
    • Baltimore, Maryland, United States, 21201-1595
      • Marlene and Stewart Greenebaum Cancer Center, University of Maryland
    • Baltimore, Maryland, United States, 21225
      • Sinai Hospital of Baltimore
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02111
      • Floating Hospital for Children
    • Springfield, Massachusetts, United States, 01107
      • Baystate Medical Center
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Memorial Medical Center - University Campus
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0914
      • Mott Children's Hospital
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan
    • Detroit, Michigan, United States, 48236
      • St. John Hospital and Medical Center
    • East Lansing, Michigan, United States, 48824
      • Michigan State University
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health and DeVos Children's Hospital
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Royal Oak, Michigan, United States, 48073-6769
      • CCOP - Beaumont
    • Royal Oak, Michigan, United States, 48073-6769
      • William Beaumont Hospital
  • Minnesota
    • Duluth, Minnesota, United States, 55805-1983
      • St. Mary's/Duluth Clinic Cancer Center
    • Minneapolis, Minnesota, United States, 55404
      • Children's Hospitals and Clinics - Minneapolis
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
    • Saint Paul, Minnesota, United States, 55102
      • Children's Hospitals and Clinics of Minnesota
  • Mississippi
    • Jackson, Mississippi, United States, 39216-4505
      • University of Mississippi Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
    • Saint Louis, Missouri, United States, 63110
      • St. Louis Children's Hospital
    • Saint Louis, Missouri, United States, 63104
      • Cardinal Glennon Children's Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Children's Hospital of Omaha
    • Omaha, Nebraska, United States, 68198-2168
      • University of Nebraska Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89109-2306
      • Sunrise Hospital and Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756-0002
      • Norris Cotton Cancer Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • New Brunswick, New Jersey, United States, 08903
      • Cancer Institute of New Jersey
    • Newark, New Jersey, United States, 07112-2094
      • Newark Beth Israel Medical Center
    • Paterson, New Jersey, United States, 07503
      • St. Joseph's Hospital and Medical Center
    • Summit, New Jersey, United States, 07901
      • Atlantic Health System
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico Cancer Research and Treatment Center
  • New York
    • Albany, New York, United States, 12208
      • Cancer Center of Albany Medical Center
    • Bronx, New York, United States, 10461
      • Albert Einstein Clinical Cancer Center
    • Brooklyn, New York, United States, 11219
      • Maimonides Medical Center
    • Brooklyn, New York, United States, 11201
      • Brooklyn Hospital Center
    • Brooklyn, New York, United States, 11203
      • State University of New York Health Science Center at Brooklyn College of Medicine
    • Brooklyn, New York, United States, 11212
      • Brookdale University Hospital and Medical Center
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • New Hyde Park, New York, United States, 11042
      • Schneider Children's Hospital
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
    • New York, New York, United States, 10021-4885
      • New York Presbyterian Hospital - Cornell Campus
    • New York, New York, United States, 10032
      • Columbia Presbyterian Hospital
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center
    • Stony Brook, New York, United States, 11790-7775
      • State University of New York Health Sciences Center - Stony Brook
    • Syracuse, New York, United States, 13210
      • State University of New York - Upstate Medical University
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Saint Joseph's Health System
    • Chapel Hill, North Carolina, United States, 27599-7295
      • Lineberger Comprehensive Cancer Center, UNC
    • Charlotte, North Carolina, United States, 28232-2861
      • Carolinas Medical Center
    • Charlotte, North Carolina, United States, 28233-3549
      • Presbyterian Healthcare
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center
    • Greenville, North Carolina, United States, 27858-4354
      • East Carolina University School of Medicine
    • Winston-Salem, North Carolina, United States, 27157-1081
      • Comprehensive Cancer Center at Wake Forest University
  • North Dakota
    • Fargo, North Dakota, United States, 58103-4940
      • Dakota Cancer Institute
  • Ohio
    • Akron, Ohio, United States, 44308
      • Children's Hospital Medical Center of Akron
    • Cincinnati, Ohio, United States, 45229-3039
      • Children's Hospital Medical Center - Cincinnati
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Cleveland, Ohio, United States, 44106-5065
      • Ireland Cancer Center
    • Columbus, Ohio, United States, 43205-2696
      • Children's Hospital of Columbus
    • Dayton, Ohio, United States, 45404
      • Children's Medical Center - Dayton
    • Toledo, Ohio, United States, 43601
      • Toledo Children's Hospital
    • Toledo, Ohio, United States, 43608
      • St. Vincent Mercy Medical Center
    • Youngstown, Ohio, United States, 44501
      • Forum Health-Tod Childrens Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Children's Hospital of Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Natalie Warren Bryant Cancer Center
    • Tulsa, Oklahoma, United States, 74136
      • CCOP - Oklahoma
  • Oregon
    • Portland, Oregon, United States, 97201-3098
      • Doernbecher Children's Hospital
    • Portland, Oregon, United States, 97227
      • Legacy Emanuel Hospital and Health Center
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822-1320
      • Geisinger Medical Center
    • Hershey, Pennsylvania, United States, 17033-0850
      • Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Philadelphia, Pennsylvania, United States, 19134-1095
      • St. Christopher's Hospital for Children
    • Pittsburgh, Pennsylvania, United States, 15213
      • Children's Hospital of Pittsburgh
  • Rhode Island
    • Providence, Rhode Island, United States, 02818
      • Rhode Island Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425-0721
      • Medical University of South Carolina
    • Columbia, South Carolina, United States, 29203
      • Palmetto Health South Carolina Cancer Center
    • Greenville, South Carolina, United States, 29605
      • Children's Hospital of Greenville Hospital System
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105-1080
      • Avera Cancer Institute
    • Sioux Falls, South Dakota, United States, 57117
      • Sioux Valley Hospital
  • Tennessee
    • Johnson City, Tennessee, United States, 37604
      • East Tennessee State University Cancer Center at JCMC
    • Knoxville, Tennessee, United States, 37901
      • East Tennessee Children's Hospital
    • Memphis, Tennessee, United States, 38105-2794
      • Saint Jude Children's Research Hospital
    • Nashville, Tennessee, United States, 37232-6838
      • Vanderbilt-Ingram Cancer Center
  • Texas
    • Amarillo, Texas, United States, 79106
      • Texas Tech University Health Sciences Center School of Medicine
    • Austin, Texas, United States, 78701
      • Children's Hospital of Austin
    • Dallas, Texas, United States, 75230
      • Medical City Dallas Hospital
    • Dallas, Texas, United States, 75235-9154
      • Simmons Cancer Center - Dallas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center - Fort Worth
    • Galveston, Texas, United States, 77555-0361
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030-4009
      • University of Texas - MD Anderson Cancer Center
    • Lackland Air Force Base, Texas, United States, 78236-5300
      • San Antonio Military Pediatric Cancer and Blood Disorders Center
    • Lubbock, Texas, United States, 79410
      • Covenant Children's Hospital
    • San Antonio, Texas, United States, 78207
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78229-3902
      • Methodist Health Care System
    • Temple, Texas, United States, 76508
      • Scott and White Memorial Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute
  • Vermont
    • Burlington, Vermont, United States, 05401-3498
      • Vermont Cancer Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Cancer Center at the University of Virginia
    • Falls Church, Virginia, United States, 22042-3300
      • Inova Fairfax Hospital
    • Norfolk, Virginia, United States, 23507
      • Children's Hospital of The King's Daughters
    • Portsmouth, Virginia, United States, 23708-5100
      • Naval Medical Center, Portsmouth
    • Richmond, Virginia, United States, 23298-0037
      • Massey Cancer Center
    • Roanoke, Virginia, United States, 24013
      • Carilion Medical Center for Children
  • Washington
    • Seattle, Washington, United States, 98105
      • Children's Hospital and Regional Medical Center - Seattle
    • Seattle, Washington, United States, 98109-1024
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98112
      • Group Health Cooperative
    • Spokane, Washington, United States, 99210-0248
      • Deaconess Medical Center
    • Tacoma, Washington, United States, 98431-5000
      • Madigan Army Medical Center
    • Tacoma, Washington, United States, 98415-0299
      • Mary Bridge Children's Health Center
  • West Virginia
    • Charleston, West Virginia, United States, 25302
      • West Virginia University - Charleston
    • Huntington, West Virginia, United States, 25701
      • Cabell-Huntington Hospital, Inc
    • Morgantown, West Virginia, United States, 26506-9300
      • West Virginia University Hospitals
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • CCOP - St. Vincent Hospital Cancer Center, Green Bay
    • Green Bay, Wisconsin, United States, 54301
      • Bellin Memorial Hospital
    • Green Bay, Wisconsin, United States, 54307-9070
      • St. Vincent Hospital
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Medical Center
    • Madison, Wisconsin, United States, 53792-0001
      • University of Wisconsin Hospital and Clinics
    • Marshfield, Wisconsin, United States, 54449-5772
      • Marshfield Clinic
    • Milwaukee, Wisconsin, United States, 53226
      • Midwest Children's Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Radiation: radiation therapy; Drug: doxorubicin hydrochloride; Other Names: Adriamycin; NSC #123127; Procedure: conventional surgery; Biological: dactinomycin; Other Names: Cosmegen; Actinomycin-D; NSC #3053; Drug: vincristine sulfate; IV; Other Names: VCR
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	Drug: cyclophosphamide; Other Names: Cytoxan; CTX; NSC #2626-71; Radiation: radiation therapy; Drug: etoposide; Other Names: VP-16; VePesid; NSC #141540; Drug: doxorubicin hydrochloride; Other Names: Adriamycin; NSC #123127; Procedure: conventional surgery; Biological: filgrastim; Other Names: Neupogen; NSC #614629; Granulocyte-colony stimulating factor; GCSF; r-MetHuG-CSF; Drug: vincristine sulfate; IV; Other Names: VCR
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	Drug: carboplatin; Other Names: CBDCA; NSC #241240; Drug: cyclophosphamide; Other Names: Cytoxan; CTX; NSC #2626-71; Radiation: radiation therapy; Drug: etoposide; Other Names: VP-16; VePesid; NSC #141540; Procedure: conventional surgery; Biological: filgrastim; Other Names: Neupogen; NSC #614629; Granulocyte-colony stimulating factor; GCSF; r-MetHuG-CSF
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event free survival	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.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event Free Survival	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.	2 years
Post-relapse survival	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.	4 years
Response rate	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%.

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Daniel M. Green, MD, Roswell Park Cancer Institute

Publications and helpful links

General Publications

• Kalapurakal JA, Perlman EJ, Seibel NL, Ritchey M, Dome JS, Grundy PE. Outcomes of patients with revised stage I clear cell sarcoma of kidney treated in National Wilms Tumor Studies 1-5. Int J Radiat Oncol Biol Phys. 2013 Feb 1;85(2):428-31. doi: 10.1016/j.ijrobp.2012.04.023. Epub 2012 Jun 1.
• Green DM, Cotton CA, Malogolowkin M, Breslow NE, Perlman E, Miser J, Ritchey ML, Thomas PR, Grundy PE, D'Angio GJ, Beckwith JB, Shamberger RC, Haase GM, Donaldson M, Weetman R, Coppes MJ, Shearer P, Coccia P, Kletzel M, Macklis R, Tomlinson G, Huff V, Newbury R, Weeks D. Treatment of Wilms tumor relapsing after initial treatment with vincristine and actinomycin D: a report from the National Wilms Tumor Study Group. Pediatr Blood Cancer. 2007 May;48(5):493-9. doi: 10.1002/pbc.20822.
• Ehrlich PF, Anderson JR, Ritchey ML, Dome JS, Green DM, Grundy PE, Perlman EJ, Kalapurakal JA, Breslow NE, Shamberger RC. Clinicopathologic findings predictive of relapse in children with stage III favorable-histology Wilms tumor. J Clin Oncol. 2013 Mar 20;31(9):1196-201. doi: 10.1200/JCO.2011.41.1165. Epub 2013 Feb 4.

Study record dates

Study Major Dates

• Study Start: January 1, 1996
• Primary Completion (ACTUAL): June 1, 2002
• Study Completion (ACTUAL): February 1, 2006

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (ESTIMATE): January 27, 2003

Study Record Updates

• Last Update Posted (ESTIMATE): July 25, 2014
• Last Update Submitted That Met QC Criteria: July 23, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: clear cell sarcoma of the kidney; rhabdoid tumor of the kidney; recurrent Wilms tumor and other childhood kidney tumors
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Genetic Diseases, Inborn; Neoplastic Syndromes, Hereditary; Neoplasms, Complex and Mixed; Kidney Neoplasms; Wilms Tumor; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Adjuvants, Immunologic; Protein Synthesis Inhibitors; Antibiotics, Antineoplastic; Cyclophosphamide; Carboplatin; Etoposide; Lenograstim; Doxorubicin; Liposomal doxorubicin; Vincristine; Dactinomycin
• Other Study ID Numbers: 9444; COG-Q9402 (OTHER: Children's Oncology Group); NWTS-Q9402 (OTHER: NWTS); CCG-4942 (OTHER: Children's Cancer Group); POG-9444 (OTHER: Pediatric Oncology Group); INT-0152; NWTS-5/R (OTHER: NWTS); CDR0000063900 (OTHER: NCI)