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Treatment of Newly Diagnosed Higher Risk Favorable Histology Wilms Tumors

Phase 3
29 Years
Open (Enrolling)
Stage III Wilms Tumor, Stage IV Wilms Tumor

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Trial Information

Treatment of Newly Diagnosed Higher Risk Favorable Histology Wilms Tumors


I. Determine the 4-year event-free survival (EFS) of patients with stage IV favorable
histology (FH) Wilms' tumor with pulmonary metastases only who have complete resolution of
pulmonary lesions without whole lung irradiation treated with DD4A chemotherapy comprising
vincristine, dactinomycin, and doxorubicin hydrochloride.

II. Determine the 4-year EFS of these patients who do not have resolution of pulmonary
metastases by week 6 treated with the addition of cyclophosphamide and etoposide to a
modified-regimen DD4A (regimen M).

III. Determine the 4-year EFS of patients with stage III or IV FH Wilms' tumor with loss of
heterozygosity for chromosomes 1p and 16q treated with regimen M.


I. Correlate the burden of pulmonary metastatic disease with outcome in patients with stage
IV FH Wilms' tumor.

OUTLINE: This is a multicenter study.

REGIMEN DD4A (weeks 1-6): Patients receive dactinomycin IV over 1-5 minutes once in week 1;
vincristine IV once in weeks 1-6; and doxorubicin hydrochloride IV over 15 minutes once in
week 4 in the absence of disease progression or unacceptable toxicity. Patients with
pulmonary and extra-pulmonary metastases at diagnosis undergo radiotherapy once daily
beginning in week 1 and continuing for 5-14 days. After completion of DD4A chemotherapy
(week 6), patients undergo evaluation. Patients with stage IV disease and pulmonary
metastases only with no loss of heterozygosity (LOH) who are rapid complete responders (RCR)
(i.e., pulmonary metastases disappear) proceed to regimen DD4A (weeks 7-25).

All other patients (i.e., patients with stage III or IV disease and LOH of both 1p and 16q;
stage IV disease with pulmonary metastases only who are slow incomplete responders [SIR]
[i.e., pulmonary metastases do not disappear]; or stage IV disease with nonpulmonary
metastases or with nonpulmonary metastases in combination with pulmonary metastases) proceed
to regimen M (weeks 7-31).

Patients with initially unresectable or incompletely resected tumors are reevaluated at week
6, and if resectable, undergo surgery and then proceed to either regimen DD4A or regimen M
as described above.

REGIMEN DD4A (weeks 7-25): Patients receive dactinomycin IV over 1-5 minutes once in weeks
7, 13, 19, and 25; vincristine IV once in weeks 7-10, 13, 16, 19, 22, and 25; and
doxorubicin hydrochloride IV over 15 minutes once in weeks 10, 16, and 22 in the absence of
disease progression or unacceptable toxicity.

REGIMEN M (weeks 7-31): Patients receive cyclophosphamide IV over 1 hour and etoposide IV
over 1 hour on days 1-5 in weeks 7, 10, 19, and 25; vincristine IV once in weeks 8, 9, 11,
12, 13, 16, 22, 28, and 31; and dactinomycin IV and doxorubicin hydrochloride IV over 15
minutes once in weeks 13, 16, 22, 28, and 31 in the absence of disease progression or
unacceptable toxicity. Patients with pulmonary metastases only who are SIR also undergo
whole lung radiotherapy once daily beginning in week 7 and continuing for 5-14 days.

NOTE: Patients who begin study treatment after undergoing resection of pulmonary metastases
are treated according to regimen DD4A (weeks 1-25) and undergo whole lung radiotherapy for
5-14 days beginning in week 1.

After completion of study treatment, patients are followed periodically for 10 years.

Inclusion Criteria:

- Newly diagnosed Wilms' tumor meeting 1 of the following criteria:

- Stage IV disease with favorable histology with or without loss of heterozygosity
(LOH) for 1p and 16q

- Stage III disease with favorable histology with LOH for 1p and 16q transferring
from clinical trial COG-AREN0532

- Patients must begin therapy within 14 days after surgery or biopsy, unless medically

- No bilateral Wilms' tumors (stage IV)

- Patients should be referred to COG-AREN0534

- Previously enrolled in clinical trial COG-AREN03B2

- Karnofsky performance status (PS) 50-100% (for patients > 16 years of age) OR Lansky
PS 50-100% (for patients ≤ 16 years of age)

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST or ALT < 2.5 times ULN

- Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by
radionuclide angiogram

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No prior tumor-directed chemotherapy or radiotherapy unless transferring from
clinical trial COG-AREN0532 OR treatment for emergent issues, as medically indicated

- No concurrent aprepitant

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

EFS of patients with stage IV and rapidly completely responding (RCR) lung metastases

Outcome Description:

The methods of Woolson to compare the results to the fixed null outcomes as defined above and using an O'Brien-Fleming boundary (truncated at 3 standard deviations) will be used.

Outcome Time Frame:

At 4 years

Safety Issue:


Principal Investigator

David Dix

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

February 2007

Completion Date:

Related Keywords:

  • Stage III Wilms Tumor
  • Stage IV Wilms Tumor
  • Wilms Tumor



Baylor College of Medicine Houston, Texas  77030
Johns Hopkins University Baltimore, Maryland  21205
Memorial Sloan Kettering Cancer Center New York, New York  10021
Cleveland Clinic Foundation Cleveland, Ohio  44195
Roswell Park Cancer Institute Buffalo, New York  14263
Mayo Clinic Rochester, Minnesota  55905
Children's Hospital of Philadelphia Philadelphia, Pennsylvania  19104
University of Iowa Hospitals and Clinics Iowa City, Iowa  52242
University of Mississippi Medical Center Jackson, Mississippi  39216-4505
Medical University of South Carolina Charleston, South Carolina  29425-0721
Tripler Army Medical Center Honolulu, Hawaii  96859-5000
Hurley Medical Center Flint, Michigan  48503
Rhode Island Hospital Providence, Rhode Island  02903
Medical City Dallas Hospital Dallas, Texas  75230
University of Texas Health Science Center at San Antonio San Antonio, Texas  78284-7811
Midwest Children's Cancer Center Milwaukee, Wisconsin  53226
Sinai Hospital of Baltimore Baltimore, Maryland  21225
Bronson Methodist Hospital Kalamazoo, Michigan  49007
Geisinger Medical Center Danville, Pennsylvania  17822-0001
Vanderbilt-Ingram Cancer Center Nashville, Tennessee  37232-6838
Loyola University Medical Center Maywood, Illinois  60153
Massachusetts General Hospital Cancer Center Boston, Massachusetts  02114
Morristown Memorial Hospital Morristown, New Jersey  07962-1956
Marshfield Clinic Marshfield, Wisconsin  54449
Loma Linda University Medical Center Loma Linda, California  92354
Baptist Hospital of Miami Miami, Florida  33176-2197
Newark Beth Israel Medical Center Newark, New Jersey  07112
New York Medical College Valhalla, New York  10595
Dana-Farber Cancer Institute Boston, Massachusetts  02115
Cedars-Sinai Medical Center Los Angeles, California  90048
University of Arkansas for Medical Sciences Little Rock, Arkansas  72205
Brooke Army Medical Center Fort Sam Houston, Texas  78234-6200
Madigan Army Medical Center Tacoma, Washington  98431-5048
Eastern Maine Medical Center Bangor, Maine  04401
William Beaumont Hospital Royal Oak, Michigan  48073
University of Nebraska Medical Center Omaha, Nebraska  68198-3330
Hackensack University Medical Center Hackensack, New Jersey  07601
Children's Hospital Los Angeles Los Angeles, California  90027-0700
Children's National Medical Center Washington, District of Columbia  20010-2970
Miami Children's Hospital Miami, Florida  33155-4069
All Children's Hospital St. Petersburg, Florida  33701
Advocate Hope Children's Hospital Oak Lawn, Illinois  60453
Saint Jude Midwest Affiliate Peoria, Illinois  61637
Ochsner Clinic Foundation New Orleans, Louisiana  70121
Carolinas Medical Center Charlotte, North Carolina  28232-2861
University of Oklahoma Health Sciences Center Oklahoma City, Oklahoma  73104
Legacy Emanuel Hospital and Health Center Portland, Oregon  97227
St. Jude Children's Research Hospital Memphis, Tennessee  38105-2794
Driscoll Children's Hospital Corpus Christi, Texas  78466
Scott and White Memorial Hospital Temple, Texas  76508
Inova Fairfax Hospital Falls Church, Virginia  22042-3300
Weill Medical College of Cornell University New York, New York  10021
Southern California Permanente Medical Group Downey, California  90242
Children's Hospital Central California Madera, California  93638-8762
Kosair Children's Hospital Louisville, Kentucky  40202-3830
Brooklyn Hospital Center Brooklyn, New York  11201
Children's Hospital Medical Center of Akron Akron, Ohio  44308
Covenant Children's Hospital Lubbock, Texas  79410
University of Wisconsin Hospital and Clinics Madison, Wisconsin  53792-0001
Overlook Hospital Summit, New Jersey  07902-0220
Winthrop University Hospital Mineola, New York  11501
Cincinnati Children's Hospital Medical Center Cincinnati, Ohio  45229-3039
Methodist Children's Hospital of South Texas San Antonio, Texas  78229-3993
Primary Children's Medical Center Salt Lake City, Utah  84113-1100
Montefiore Medical Center Bronx, New York  10467-2490
Saint Peter's University Hospital New Brunswick, New Jersey  08901-1780
Rady Children's Hospital - San Diego San Diego, California  92123-4282
Children's Hospitals and Clinics of Minnesota - Minneapolis Minneapolis, Minnesota  55404
University of New Mexico Cancer Center Albuquerque, New Mexico  87131-5636
Nationwide Children's Hospital Columbus, Ohio  43205-2696
Children's Hospital of Pittsburgh of UPMC Pittsburgh, Pennsylvania  15213
Dell Children's Medical Center of Central Texas Austin, Texas  78723
Children's Hospital and Research Center at Oakland Oakland, California  94609-1809
Mary Bridge Children's Hospital and Health Center Tacoma, Washington  98415-0299
Lehigh Valley Hospital - Muhlenberg Bethlehem, Pennsylvania  18017
Presbyterian Hospital Charlotte, North Carolina  28233-3549
Lee Memorial Health System Fort Myers, Florida  33902
University of Virginia Charlottesville, Virginia  22908
University of Alabama at Birmingham Birmingham, Alabama  35294-3300
Children's Hospital of Alabama Birmingham, Alabama  35233
Connecticut Children's Medical Center Hartford, Connecticut  06106
University of North Carolina Chapel Hill, North Carolina  27599
Duke University Medical Center Durham, North Carolina  27710
University of Florida Gainesville, Florida  32610-0277
University of Rochester Rochester, New York  14642
Nemours Children's Clinic - Pensacola Pensacola, Florida  32504
Helen DeVos Children's Hospital at Spectrum Health Grand Rapids, Michigan  49503
Yale University New Haven, Connecticut  06520
Wayne State University Detroit, Michigan  48202
Mercy Children's Hospital Toledo, Ohio  43608
Legacy Emanuel Children's Hospital Portland, Oregon  97227
BI-LO Charities Children's Cancer Center Greenville, South Carolina  29605
University of Arizona Health Sciences Center Tucson, Arizona  85724
University of Massachusetts Medical School Worcester, Massachusetts  01605
Dartmouth Hitchcock Medical Center Lebanon, New Hampshire  03756
University Of Vermont Burlington,, Vermont  05403
Albany Medical Center Albany, New York  12208
University of Texas Southwestern Medical Center Dallas, Texas  
University of Kentucky Lexington, Kentucky  40536-0098
UC Davis Comprehensive Cancer Center Sacramento, California  95817
Oregon Health and Science University Portland, Oregon  97201
Tulane University Health Sciences Center New Orleans, Louisiana  70112
Virginia Commonwealth University Richmond, Virginia  
Florida Hospital Orlando, Florida  32803
Memorial Health University Medical Center Savannah, Georgia  31404
University of Chicago Comprehensive Cancer Center Chicago, Illinois  60637-1470
Seattle Children's Hospital Seattle, Washington  98105
Wake Forest University Health Sciences Winston-Salem, North Carolina  27157
Childrens Memorial Hospital Chicago, Illinois  60614
Kaiser Permanente-Oakland Oakland, California  94611
Sutter General Hospital Sacramento, California  95816
Lombardi Comprehensive Cancer Center at Georgetown University Washington, District of Columbia  20057
M D Anderson Cancer Center- Orlando Orlando, Florida  32806
University of Hawaii Honolulu, Hawaii  96813
Saint Luke's Mountain States Tumor Institute Boise, Idaho  83712
Saint Vincent Hospital and Health Services Indianapolis, Indiana  46260
Saint John Hospital and Medical Center Detroit, Michigan  48236
Michigan State University - Breslin Cancer Center East Lansing, Michigan  48824-1313
Kalamazoo Center for Medical Studies Kalamazoo, Michigan  49008
Saint John's Mercy Medical Center Saint Louis, Missouri  63141
Nevada Cancer Research Foundation CCOP Las Vegas, Nevada  89106
Columbia University Medical Center New York, New York  10032
State University of New York Upstate Medical University Syracuse, New York  13210
Mission Hospitals Inc Asheville, North Carolina  28801
Natalie W Bryant Cancer Center Tulsa, Oklahoma  74136
University of Maryland Greenebaum Cancer Center Baltimore, Maryland  21201
University of South Alabama Mobile, Alabama  36693
University of Illinois Chicago, Illinois  60612
Stony Brook University Medical Center Stony Brook, New York  11794
Cook Children's Medical Center Fort Worth, Texas  76104
Memorial Healthcare System - Joe DiMaggio Children's Hospital Hollywood, Florida  33021
East Carolina University Greenville, North Carolina  27858
West Virginia University Charleston Charleston, West Virginia  25304
The Children's Medical Center of Dayton Dayton, Ohio  45404
Advocate Lutheran General Hospital Park Ridge, Illinois  60068
University of Miami Miller School of Medicine-Sylvester Cancer Center Miami, Florida  33136
University of Minnesota Medical Center-Fairview Minneapolis, Minnesota  55455
Children's Oncology Group Arcadia, California  91006-3776
C S Mott Children's Hospital Ann Arbor, Michigan  48109
Southern Illinois University Springfield, Illinois  62702
University Of Missouri-Columbia Columbia, Missouri  65212
Walter Reed National Military Medical Center Bethesda, Maryland  20889
Riley Hospital for Children Indianapolis, Indiana  46202
Cardinal Glennon Children's Medical Center St. Louis, Missouri  63104
UMDNJ - Robert Wood Johnson University Hospital New Brunswick, New Jersey  08903
Phoenix Childrens Hospital Phoenix, Arizona  85016
Miller Children's Hospital Long Beach, California  90806
Childrens Hospital of Orange County Orange, California  92868-3874
Alfred I duPont Hospital for Children Wilmington, Delaware  19803
Nemours Children's Clinic - Jacksonville Jacksonville, Florida  32207-8426
Nemours Childrens Clinic - Orlando Orlando, Florida  32806
Saint Joseph Children's Hospital of Tampa Tampa, Florida  33607
Children's Healthcare of Atlanta - Egleston Atlanta, Georgia  30322
The Childrens Mercy Hospital Kansas City, Missouri  64108
Rainbow Babies and Childrens Hospital Cleveland, Ohio  44106
Penn State Hershey Children's Hospital Hershey, Pennsylvania  17033
Palmetto Health Richland Columbia, South Carolina  29203
East Tennessee Childrens Hospital Knoxville, Tennessee  37916
Saint Mary's Hospital West Palm Beach, Florida  33407
Children's Hospital and Medical Center of Omaha Omaha, Nebraska  68114
Saint Joseph's Regional Medical Center Paterson, New Jersey  07503
Texas Tech University Health Science Center-Amarillo Amarillo, Texas  79106
Childrens Hospital-King's Daughters Norfolk, Virginia  23507
Sanford Medical Center-Fargo Fargo, North Dakota  58122
Children's Hospital Colorado Aurora, Colorado  80045
Floating Hospital for Children at Tufts Medical Center Boston, Massachusetts  02111
Lucile Packard Children's Hospital Stanford University Palo Alto, California  94304
University of California San Francisco Medical Center-Parnassus San Francisco, California  94143
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center Denver, Colorado  80218
Raymond Blank Children's Hospital Des Moines, Iowa  50309
Children's Hospital-Main Campus New Orleans, Louisiana  70118
The Toledo Hospital/Toledo Children's Hospital Toledo, Ohio  43606
Saint Christopher's Hospital for Children Philadelphia, Pennsylvania  19134
Greenville Cancer Treatment Center Greenville, South Carolina  29605
Sanford USD Medical Center - Sioux Falls Sioux Falls, South Dakota  57117-5134
T C Thompson Children's Hospital Chattanooga, Tennessee  37403
Carilion Clinic Children's Hospital Roanoke, Virginia  24014
Providence Sacred Heart Medical Center and Children's Hospital Spokane, Washington  99204
Broward Health Medical Center Fort Lauderdale, Florida  33316
The Steven and Alexandra Cohen Children's Medical Center of New York New Hyde Park, New York  11040