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Treatment for Patients With Bilateral, Multicentric, or Bilaterally-Predisposed Unilateral Wilms Tumor


Phase 3
N/A
29 Years
Open (Enrolling)
Both
Diffuse Hyperplastic Perilobar Nephroblastomatosis, Rhabdoid Tumor of the Kidney, Stage I Wilms Tumor, Stage II Wilms Tumor, Stage III Wilms Tumor, Stage IV Wilms Tumor, Stage V Wilms Tumor

Thank you

Trial Information

Treatment for Patients With Bilateral, Multicentric, or Bilaterally-Predisposed Unilateral Wilms Tumor


OBJECTIVES:

I. To improve 4-year event-free survival (EFS) to 73% for young patients with bilateral
Wilms tumor (BWT).

II. To prevent complete removal of at least one kidney in 50% of patients with BWT by using
prenephrectomy 3-drug chemotherapy induction with vincristine (vincristine sulfate),
dactinomycin, and doxorubicin (doxorubicin hydrochloride).

III. To evaluate the efficacy of chemotherapy in preserving renal units in children with
diffuse hyperplastic perilobar nephroblastomatosis (DHPLN) and preventing Wilms tumor
development.

IV. To facilitate partial nephrectomy in lieu of nephrectomy in 25% of children with
unilateral tumors and aniridia, Beckwith-Wiedemann syndrome (BWS), hemihypertrophy or other
overgrowth syndromes, by using prenephrectomy 2-drug chemotherapy induction with vincristine
and dactinomycin.

V. To have 75% of patients with BWT undergo definitive surgical treatment by 12 weeks after
initiation of chemotherapy.

OUTLINE:

PREOPERATIVE CHEMOTHERAPY: Patients receive preoperative chemotherapy according to histology
and stage.

VAD REGIMEN (stage I-IV bilateral Wilms tumor [BWT] with biopsy revealing favorable
histology or no preoperative biopsy; stage I-III BWT with focal anaplasia; stage I BWT with
diffuse anaplasia; or high-risk, stage III-IV unilateral Wilms tumor [WT] with contralateral
nephrogenic rest [NR] or predisposition syndrome): Patients receive vincristine sulfate IV
on days 1, 8, 15, 22, 29, and 36 (weeks 1-6) and dactinomycin IV and doxorubicin
hydrochloride IV over 15-120 minutes on days 1 and 22 (weeks 1 and 4).

REVISED UH-1 REGIMEN (stage IV BWT with focal anaplasia; stage II-IV BWT with diffuse
anaplasia; or stage I-IV malignant rhabdoid tumor of the kidney): Patients receive
vincristine sulfate IV on days 1, 8, and 15 (weeks 1-3); doxorubicin hydrochloride IV over
15-120 minutes on day 1 (week 1); cyclophosphamide IV over 1 hour on day 1 and on days 22-25
(weeks 1 and 4); carboplatin IV over 1 hour on day 22 (week 4); and etoposide phosphate IV
over 1 hour on days 22-25 (week 4).

EE-4A REGIMEN (high-risk, stage I-II unilateral WT with contralateral NR or predisposition
syndrome or diffuse hyperplastic perilobar NRs [DHPLNR]): Patients receive vincristine
sulfate IV over 1 minute on days 1, 8, 15, 22, 29, and 36 (weeks 1-6) and dactinomycin IV
over 1-5 minutes on days 1 and 22 (weeks 1 and 4).

Patients are evaluated at week 6. If partial nephrectomy is feasible, patients proceed to
definitive surgery and lymph node sampling followed by postoperative therapy. If partial
nephrectomy is not feasible, patients receive additional chemotherapy (as above with the
same or a different set of regimen) followed by definitive surgery at week 12 and
postoperative therapy OR patients proceed to a different chemotherapy regimen.

POSTOPERATIVE THERAPY: Patients receive postoperative therapy according to histology after
preoperative chemotherapy and according to the highest assigned risk for either kidney.

EE-4A regimen (BWT with complete resection of all gross tumors at diagnosis with stage I-II
favorable histology; BWT with complete response [CR] by imaging after 6 weeks of
preoperative chemotherapy; completely necrotic stage I-II BWT; intermediate-risk stage I
BWT; unilateral WT stage I-II with CR by imaging after 6-12 weeks of preoperative
chemotherapy; completely necrotic stage I-II unilateral WT; or intermediate-risk stage I-II
unilateral WT): Patients receive vincristine sulfate IV over 1 minute on days 43, 50, 57,
64, 85, 106, and 127 (weeks 7-10, 13, 16, and 19) and dactinomycin IV over 1-5 minutes on
days 43, 64, 85, 106, and 127 (weeks 7, 10, 13, 16, and 19).

DD-4A REGIMEN (intermediate-risk, stage II BWT; stage I BWT with blastemal predominance; or
stage I unilateral WT with blastemal predominance): Patients receive vincristine sulfate IV
over 1 minute on days 1, 8, 15, 22, 29, and 36 (weeks 1-6); dactinomycin IV over 1-5 minutes
on day 1 (week 1); and doxorubicin hydrochloride IV over 15-120 minutes on day 22 (week 4).
Patients then receive vincristine sulfate IV over 1 minute on days 43, 50, 57, 64, 85, 106,
127, 148, and 169 (weeks 7-10, 13, 16, 19, 22, and 25); dactinomycin IV over 1-5 minutes on
days 43, 85, 127, and 169 (weeks 7, 13, 19, and 25); and doxorubicin hydrochloride over
15-120 minutes on days 63, 106, and 148 (weeks 10, 16, and 22). Some patients may also
undergo radiotherapy.

DD-4A REGIMEN AND RADIOTHERAPY (BWT with complete resection of all gross tumors at diagnosis
with stage III-IV favorable histology, completely necrotic stage III-IV BWT;
intermediate-risk, stage III-IV BWT; stage I BWT with diffuse anaplasia; stage I-III BWT
with focal anaplasia; stage I unilateral WT with diffuse anaplasia; stage I unilateral WT
with focal anaplasia; or intermediate-risk, stage III-IV unilateral WT): Patients receive
DD-4A regimen as above. Patients also undergo concurrent radiotherapy.

REGIMEN I (stage II BWT with blastemal predominance or stage II unilateral WT with blastemal
predominance): Patients receive vincristine sulfate IV over 1 minute on days 43, 50, 57, 71,
78, 85, 92, 127, and 169 (weeks 7-9, 11-14, 19, and 25); doxorubicin hydrochloride IV over
15-120 minutes on days 43, 85, 127, and 169 (weeks 7, 13, 19, and 25); cyclophosphamide IV
over 15-30 minutes on days 43, 64, 85, 106, 127, 148, and 169 (weeks 7, 10, 13, 16, 19, 22,
and 25); and etoposide phosphate IV over 1 hour on days 64, 106, and 148 (weeks 10, 16, and
22).

REGIMEN I AND RADIOTHERAPY (stage III-IV BWT with blastemal predominance or stage III-IV
unilateral WT with blastemal predominance): Patients receive regimen I as above. Patients
also undergo concurrent radiotherapy.

REVISED UH-1 REGIMEN AND RADIOTHERAPY (stage IV BWT with focal anaplasia; stage II-IV BWT
with diffuse anaplasia; stage IV unilateral WT with focal anaplasia; stage II-IV unilateral
WT with diffuse anaplasia; and stage I-IV malignant rhabdoid tumor of the kidney; or DHPLNR
with anaplasia): Patients receive vincristine sulfate IV over 1 minute on days 64, 71, 78,
85, 92, 99, 148, 155, 162, 190, 197, and 204 (weeks 10-15, 22-24, and 28-30); doxorubicin
hydrochloride IV over 15-120 minutes on days 64, 85, 148, and 190 (weeks 10, 13, 22, and
28); cyclophosphamide IV over 15-30 minutes on days 43-46, 64, 85, 106-109, 127-130, 148,
169-172, and 190 (weeks 7, 10, 13, 16, 19, 22, 25, and 28); carboplatin IV over 1 hour on
days 43, 106, 127, and 169 (weeks 7, 16, 19, and 25); and etoposide phosphate IV over 1 hour
on days 43-46, 106-109, 127-130, and 169-172 (weeks 7, 16, 19, and 25). Patients also
undergo radiotherapy.

VAD REGIMEN (DHPLNR with favorable histology WT with viable elements): Patients receive
vincristine sulfate IV over 1 minute on days 43, 50, 57, 64, 71, and 78 (weeks 7-12) and
dactinomycin IV over 1-5 minutes and doxorubicin hydrochloride IV over 15-120 minutes on
days 43 and 64 (weeks 7 and 10).

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


Inclusion Criteria:



- Diagnosis of 1 of the following:

- Synchronous bilateral Wilms tumors**; or

- Unilateral Wilms tumor and aniridia, Beckwith-Wiedemann Syndrome, idiopathic
hemihypertrophy, Simpson-Golabi-Behmel-Syndrome, Denys-Drash Syndrome or other
associated genitourinary anomalies associated with bilateral Wilms tumor, such
as hypospadias and undescended testis (to be eligible, these patients must not
undergo any nephrectomy at diagnosis; note-horseshoe kidney is not associated
with bilateral Wilms tumor and these patients should go on the appropriate
unilateral Wilms tumor study); or

- Multicentric Wilms tumor (any age) (to be eligible, these patients must not
undergo any nephrectomy at diagnosis); or

- Unilateral Wilms tumor with contralateral nephrogenic rest(s) (any size) in a
child under one year of age (to be eligible, these patients must not undergo any
nephrectomy at diagnosis); or

- Diffuse hyperplastic perilobar nephroblastomatosis (unilateral or bilateral)
defined by central radiological review; or

- Wilms tumor arising in a solitary kidney (patients with metachronous Wilms tumor
are not eligible)

- The AREN0534 study uses the guideline that Wilms tumor with a single lesion
1 cm or greater in the contralateral kidney or multiple lesions (of any
size) in the contralateral kidney should be treated on the synchronous
bilateral Wilms tumor stratum; patients with an isolated lesion less than 1
cm in the contralateral kidney should be treated on the appropriate study
for unilateral Wilms tumor OR on the unilateral Wilms tumor/contralateral
nephrogenic rest stratum of this study if they have not undergone
nephrectomy and are under one year of age

- Loss of heterozygosity (LOH) results—which are used in the unilateral Wilms
tumor studies—are not a requirement for enrollment on AREN0534; blood samples
can be submitted but will not be used to direct AREN0534 therapy

- Patients with BWT who underwent total or partial nephrectomy at diagnosis are
eligible

- Previously enrolled in 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)

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age

- AST or ALT < 2.5 times ULN for age

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

- (Cardiac function does not need to be assessed in patients who will not receive
doxorubicin as part of their initial therapy on this study [i.e., patients who
start on Regimen EE-4A])

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No prior systemic chemotherapy or radiotherapy prior to treatment on this study

- Patients with unilateral Wilms tumor and aniridia, Beckwith-Wiedemann Syndrome,
idiopathic hemihypertrophy, Simpson-Golabi-Behmel-Syndrome, Denys-Drash Syndrome or
other associated genitourinary anomalies; or multicentric or unilateral Wilms tumor
with contralateral nephrogenic rest(s) (any size) in a child under 1 year of age who
undergo a nephrectomy at diagnosis are not eligible for this study and should be
directed to a unilateral Wilms tumor study

- No concurrent aprepitant

- All patients and/or their parents or legal guardians must sign a written informed
consent

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Event-free survival

Outcome Time Frame:

4 years

Safety Issue:

No

Principal Investigator

Peter Ehrlich

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

AREN0534

NCT ID:

NCT00945009

Start Date:

July 2009

Completion Date:

Related Keywords:

  • Diffuse Hyperplastic Perilobar Nephroblastomatosis
  • Rhabdoid Tumor of the Kidney
  • Stage I Wilms Tumor
  • Stage II Wilms Tumor
  • Stage III Wilms Tumor
  • Stage IV Wilms Tumor
  • Stage V Wilms Tumor
  • Hyperplasia
  • Kidney Neoplasms
  • Wilms Tumor
  • Rhabdoid Tumor

Name

Location

Baylor College of MedicineHouston, Texas  77030
Cleveland Clinic FoundationCleveland, Ohio  44195
Roswell Park Cancer InstituteBuffalo, New York  14263
Mayo ClinicRochester, Minnesota  55905
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
University of Mississippi Medical CenterJackson, Mississippi  39216-4505
Washington University School of MedicineSaint Louis, Missouri  63110
Medical City Dallas HospitalDallas, Texas  75230
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
Midwest Children's Cancer CenterMilwaukee, Wisconsin  53226
Sinai Hospital of BaltimoreBaltimore, Maryland  21225
Bronson Methodist HospitalKalamazoo, Michigan  49007
Morristown Memorial HospitalMorristown, New Jersey  07962-1956
Marshfield ClinicMarshfield, Wisconsin  54449
Loma Linda University Medical CenterLoma Linda, California  92354
Baptist Hospital of MiamiMiami, Florida  33176-2197
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
Brooke Army Medical CenterFort Sam Houston, Texas  78234-6200
Madigan Army Medical CenterTacoma, Washington  98431-5048
Eastern Maine Medical CenterBangor, Maine  04401
Hackensack University Medical CenterHackensack, New Jersey  07601
Children's Hospital Los AngelesLos Angeles, California  90027-0700
Children's National Medical CenterWashington, District of Columbia  20010-2970
All Children's HospitalSt. Petersburg, Florida  33701
Saint Jude Midwest AffiliatePeoria, Illinois  61637
Maine Children's Cancer ProgramScarborough, Maine  04074-9308
Carolinas Medical CenterCharlotte, North Carolina  28232-2861
University of Oklahoma Health Sciences CenterOklahoma City, Oklahoma  73104
Legacy Emanuel Hospital and Health CenterPortland, Oregon  97227
St. Jude Children's Research HospitalMemphis, Tennessee  38105-2794
Driscoll Children's HospitalCorpus Christi, Texas  78466
Southern California Permanente Medical GroupDowney, California  90242
Children's Hospital Central CaliforniaMadera, California  93638-8762
Kosair Children's HospitalLouisville, Kentucky  40202-3830
Children's Hospital Medical Center of AkronAkron, Ohio  44308
Covenant Children's HospitalLubbock, Texas  79410
Overlook HospitalSummit, New Jersey  07902-0220
Mount Sinai Medical CenterNew York, New York  10029
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Methodist Children's Hospital of South TexasSan Antonio, Texas  78229-3993
Primary Children's Medical CenterSalt Lake City, Utah  84113-1100
Montefiore Medical CenterBronx, New York  10467-2490
Saint Peter's University HospitalNew Brunswick, New Jersey  08901-1780
Rady Children's Hospital - San DiegoSan Diego, California  92123-4282
Children's Hospitals and Clinics of Minnesota - MinneapolisMinneapolis, Minnesota  55404
Nationwide Children's HospitalColumbus, Ohio  43205-2696
Children's Hospital of Pittsburgh of UPMCPittsburgh, Pennsylvania  15213
Children's Hospital and Research Center at OaklandOakland, California  94609-1809
Mary Bridge Children's Hospital and Health CenterTacoma, Washington  98415-0299
Lehigh Valley Hospital - MuhlenbergBethlehem, Pennsylvania  18017
Presbyterian HospitalCharlotte, North Carolina  28233-3549
Lee Memorial Health SystemFort Myers, Florida  33902
University of VirginiaCharlottesville, Virginia  22908
University of Alabama at BirminghamBirmingham, Alabama  35294-3300
Children's Hospital of AlabamaBirmingham, Alabama  35233
Connecticut Children's Medical CenterHartford, Connecticut  06106
University of North CarolinaChapel Hill, North Carolina  27599
Duke University Medical CenterDurham, North Carolina  27710
Nemours Children's Clinic - PensacolaPensacola, Florida  32504
Helen DeVos Children's Hospital at Spectrum HealthGrand Rapids, Michigan  49503
Wayne State UniversityDetroit, Michigan  48202
Mercy Children's HospitalToledo, Ohio  43608
Legacy Emanuel Children's HospitalPortland, Oregon  97227
BI-LO Charities Children's Cancer CenterGreenville, South Carolina  29605
University of Arizona Health Sciences CenterTucson, Arizona  85724
Dartmouth Hitchcock Medical CenterLebanon, New Hampshire  03756
University Of VermontBurlington,, Vermont  05403
University of Texas Southwestern Medical CenterDallas, Texas  
University of KentuckyLexington, Kentucky  40536-0098
University of New MexicoAlbuquerque, New Mexico  87131
Tulane University Health Sciences CenterNew Orleans, Louisiana  70112
Virginia Commonwealth UniversityRichmond, Virginia  
Florida HospitalOrlando, Florida  32803
Memorial Health University Medical CenterSavannah, Georgia  31404
Seattle Children's HospitalSeattle, Washington  98105
Wake Forest University Health SciencesWinston-Salem, North Carolina  27157
Childrens Memorial HospitalChicago, Illinois  60614
Lombardi Comprehensive Cancer Center at Georgetown UniversityWashington, District of Columbia  20057
M D Anderson Cancer Center- OrlandoOrlando, Florida  32806
Saint Luke's Mountain States Tumor InstituteBoise, Idaho  83712
Michigan State University - Breslin Cancer CenterEast Lansing, Michigan  48824-1313
Kalamazoo Center for Medical StudiesKalamazoo, Michigan  49008
Saint John's Mercy Medical CenterSaint Louis, Missouri  63141
Nevada Cancer Research Foundation CCOPLas Vegas, Nevada  89106
Columbia University Medical CenterNew York, New York  10032
State University of New York Upstate Medical UniversitySyracuse, New York  13210
Mission Hospitals IncAsheville, North Carolina  28801
Saint Vincent HospitalGreen Bay, Wisconsin  54301
University of Maryland Greenebaum Cancer CenterBaltimore, Maryland  21201
Cook Children's Medical CenterFort Worth, Texas  76104
Memorial Healthcare System - Joe DiMaggio Children's HospitalHollywood, Florida  33021
West Virginia University CharlestonCharleston, West Virginia  25304
The Children's Medical Center of DaytonDayton, Ohio  45404
C S Mott Children's HospitalAnn Arbor, Michigan  48109
Riley Hospital for ChildrenIndianapolis, Indiana  46202
UMDNJ - Robert Wood Johnson University HospitalNew Brunswick, New Jersey  08903
Miller Children's HospitalLong Beach, California  90806
Childrens Hospital of Orange CountyOrange, California  92868-3874
Alfred I duPont Hospital for ChildrenWilmington, Delaware  19803
Nemours Children's Clinic - JacksonvilleJacksonville, Florida  32207-8426
Nemours Childrens Clinic - OrlandoOrlando, Florida  32806
Saint Joseph Children's Hospital of TampaTampa, Florida  33607
Children's Healthcare of Atlanta - EglestonAtlanta, Georgia  30322
The Childrens Mercy HospitalKansas City, Missouri  64108
Rainbow Babies and Childrens HospitalCleveland, Ohio  44106
Penn State Hershey Children's HospitalHershey, Pennsylvania  17033
Palmetto Health RichlandColumbia, South Carolina  29203
East Tennessee Childrens HospitalKnoxville, Tennessee  37916
Saint Mary's HospitalWest Palm Beach, Florida  33407
Texas Tech University Health Science Center-AmarilloAmarillo, Texas  79106
Childrens Hospital-King's DaughtersNorfolk, Virginia  23507
Sanford Medical Center-FargoFargo, North Dakota  58122
Children's Hospital ColoradoAurora, Colorado  80045
Floating Hospital for Children at Tufts Medical CenterBoston, Massachusetts  02111
Lucile Packard Children's Hospital Stanford UniversityPalo Alto, California  94304
University of California San Francisco Medical Center-ParnassusSan Francisco, California  94143
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical CenterDenver, Colorado  80218
Children's Hospital-Main CampusNew Orleans, Louisiana  70118
The Toledo Hospital/Toledo Children's HospitalToledo, Ohio  43606
Saint Christopher's Hospital for ChildrenPhiladelphia, Pennsylvania  19134
Greenville Cancer Treatment CenterGreenville, South Carolina  29605
Sanford USD Medical Center - Sioux FallsSioux Falls, South Dakota  57117-5134
Providence Sacred Heart Medical Center and Children's HospitalSpokane, Washington  99204
Broward Health Medical CenterFort Lauderdale, Florida  33316