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Treatment of High Risk Renal Tumors


Phase 2
N/A
29 Years
Open (Enrolling)
Both
Kidney Cancer

Thank you

Trial Information

Treatment of High Risk Renal Tumors


OBJECTIVES:

Primary

- Evaluate whether a treatment regimen containing cyclophosphamide, carboplatin, and
etoposide alternating with vincristine, doxorubicin hydrochloride, and cyclophosphamide
(revised regimen UH-1) improves the event-free and overall survival of patients with
diffuse anaplastic Wilms tumor (DAWT) as compared to historical controls.

- Evaluate, in a phase II "window" study, the antitumor activity of a combination of
vincristine and protracted-schedule irinotecan hydrochloride in patients with
metastatic DAWT.

- Evaluate whether revised regimen UH-1 improves the event-free and overall survival of
patients with malignant rhabdoid tumor (MRT) as compared to historical controls.

- Maintain the excellent event-free survival of patients with stage I clear cell sarcoma
of the kidney (CCSK) without the use of abdominal irradiation.

Secondary

- Describe the outcomes of patients with stage I DAWT or stages I-III focal anaplastic
Wilms tumor (FAWT) treated with vincristine, dactinomycin, doxorubicin hydrochloride,
and flank radiation.

- Describe the outcomes of patients with stage IV FAWT or stage IV CCSK treated with
revised regimen UH-1.

- Describe event-free and overall survival of children and adolescents with localized
renal cell carcinoma (RCC) (including patients with local lymph node involvement)
treated with surgical resection without adjuvant therapy.

- Describe response rate, event-free survival, and overall survival of patients with
unresectable or distantly metastatic RCC treated according to institutional preference.

- Correlate histologic and molecular cytogenetic findings with outcome in pediatric RCC.
(exploratory)

- Evaluate the frequency of germline and inherited INI1 mutations in renal and extrarenal
MRT and correlate the presence of detectable INI1 mutation with clinical outcome.
(exploratory)

- Determine the frequency of TP53 mutations in anaplastic Wilms tumor and correlate the
presence of detectable TP53 mutation with clinical outcome. (exploratory)

OUTLINE: This is a multicenter study. Patients are assigned to 1 of 6 treatment regimens
according to tumor histology, stage of disease, and response to treatment.

- Surgery (renal cell carcinoma [RCC]): Patients with completely resectable stage I-IV
RCC undergo surgical resection. Patients with incompletely resectable stage III-IV RCC
undergo treatment as per physician's choice.

- Patients with initially unresectable or incompletely resected tumors receive
chemotherapy and undergo imaging reevaluation after 4 cycles (approximately 12
weeks). If the tumor is deemed resectable at week 13, surgery is performed.

- Revised Regimen UH-1 (stage II-III or stage IV [with no measurable disease] diffuse
anaplastic Wilms tumor [DAWT], stage I-IV malignant rhabdoid tumor [MRT], stage IV
focal anaplastic Wilms tumor [FAWT], or stage IV clear cell sarcoma of the kidney
[CCSK]): Patients receive vincristine IV on day 1 in weeks 1-3, 10-12, 13-15, 22-24,
and 28-30; doxorubicin hydrochloride IV over 15 minutes on day 1 and cyclophosphamide
(CPM2) IV over 15-30 minutes on day 1 in weeks 1, 10, 13, 22, and 28; and
cyclophosphamide (at lower doses [CPM1]) IV over 1 hour and etoposide IV over 1 hour on
days 1-4 and carboplatin IV over 1 hour on day 1 in weeks 4, 7, 16, 19, and 25.
Patients whose primary tumors were initially resected undergo radiotherapy** once
daily, 5 days a week, for 4-5½ weeks beginning on day 1 in week 1. Patients with
delayed primary tumor resection undergo radiotherapy** beginning on day 1 in week 13.
If the primary tumor was not previously resected, patients undergo resection, if
feasible, in week 13. Patients with unresectable CCSK receive no further study therapy.

- Irinotecan/vincristine window therapy* (stage IV DAWT with measurable disease at
diagnosis): Patients receive vincristine IV on day 1 and irinotecan hydrochloride IV
over 60-90 minutes on days 1-5 in weeks 1 and 2. Patients with progressive disease (PD)
are treated with revised regimen UH-1. Patients with stable disease (SD), partial
response (PR), or complete response (CR) receive another course of irinotecan
hydrochloride/vincristine window therapy beginning on day 22. After the second course,
patients with SD or PD are treated with revised regimen UH-1 and patients with PR or CR
are treated with revised regimen UH-2.

NOTE: *Patients who are eligible for but who are unwilling to receive window therapy,
receive therapy on revised regimen UH-1.

- Some patients will have received pre-operative chemotherapy on AREN0532 or AREN0533 for
what was presumed to be favorable histology Wilms tumor. Patients designated to receive
revised regimen UH-1 receive this regimen in its entirety starting from week 1, except
that the week-28 doxorubicin dose is withheld to maintain a cumulative doxorubicin dose
≤ 225 mg/m^2.

- Revised Regimen UH-2 (DAWT with CR/PR to irinotecan hydrochloride/vincristine
window therapy): Patients receive vincristine on day 1 in weeks 1-3, 10, 11,
16-21, 25, 26, 28-30, and 34-36 and doxorubicin hydrochloride and CPM2 as in
revised regimen UH-1 in weeks 1, 16, 19, 28, and 34. Patients also receive CPM1,
etoposide, and carboplatin as in revised regimen UH-1 in weeks 4, 7, 13, 22, and
31 and irinotecan hydrochloride IV over 60-90 minutes on days 1-5 in weeks 10, 11,
25, and 26. Patients whose primary tumors were initially resected undergo
radiotherapy** as in revised regimen UH-1 beginning on day 1 in week 1. Patients
with delayed primary tumor resection undergo radiotherapy** as in revised regimen
UH-1 beginning on day 1 in week 7. If the primary tumor was not previously
resected, patients undergo resection, if feasible, in week 7.

- Regimen I (stage I-III CCSK): Patients receive vincristine IV on day 1 in weeks
1-3, 5-9, 8-9, 11-14, 19, and 25; doxorubicin hydrochloride IV over 15 minutes on
day 1 and cyclophosphamide IV over 1 hour on days 1-3 in weeks 1, 7, 13, 19, and
25; and cyclophosphamide IV and etoposide IV on days 1-5 in weeks 4, 10, 16, and
22. Patients whose primary tumors were initially resected (except those with stage
I CCSK) undergo radiotherapy** as in revised regimen UH-1 beginning on day 1 in
week 1. Patients with delayed primary tumor resection undergo radiotherapy** as in
revised regimen UH-1 beginning on day 1 in week 13. If the primary tumor was not
previously resected, patients undergo resection, if feasible, in week 13.

- Regimen DD-4A (stage I DAWT or stages I-III FAWT): Patients receive dactinomycin
IV over 1-5 minutes on day 1 in weeks 1, 7, 13, 19, and 25; vincristine IV on day
1 in weeks 1-10, 13, 16, 19, 22, and 25; and doxorubicin hydrochloride IV over 15
minutes on day 1 in weeks 4, 10, 16, and 22. Patients whose primary tumors were
initially resected undergo radiotherapy** as in revised regimen UH-1 beginning on
day 1 in week 1. Patients with delayed primary tumor resection undergo
radiotherapy** as in revised regimen UH-1 beginning on day 1 in week 13. If the
primary tumor was not previously resected, patients undergo resection, if
feasible, in week 13.

- Patients designated to receive Regimen DD-4A may resume this regimen where they left
off on the AREN0532 or AREN0533 studies. For example, if a patient received 6 weeks of
DD-4A therapy on AREN0532 and then had a nephrectomy showing FAWT, they may transfer to
AREN0321 and resume therapy at week 7.

NOTE: **Radiation therapy should be delayed for patients less than 6 months of age.

Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up until the fifth anniversary of
the date the patient was enrolled on this study.

PROJECTED ACCRUAL: A total of 295 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Newly diagnosed disease of 1 of the following histologic types:

- Focal anaplastic Wilms' tumor

- Diffuse anaplastic Wilms' tumor

- Clear cell sarcoma of the kidney

- Malignant rhabdoid tumor (renal or extrarenal)

- Renal cell carcinoma

- Clear cell

- Papillary

- Renal medullary

- Oncocytoid

- Sarcomatoid

- Chromophobe

- Translocation

- Collecting duct

- Carcinoma associated with neuroblastoma

- Renal cell carcinoma unclassified

- High-risk disease

- Stage I-IV disease

- No stage V (bilateral) high-risk renal tumors

- Patients with stage IV diffuse anaplastic Wilms tumor are eligible for "window"
therapy if the following criteria are met:

- Measurable disease, defined as ≥ 1 lesion that can be measured in 3 dimensions
with the longest diameter (which may be in the cranio-caudal dimension) ≥ 1 cm
on CT scan or MRI

- No tumors that could potentially cause life-threatening complications with tumor
progression, such as tumors with intracranial or intraspinal extension

- No tumors that could compress the airway

- No CNS tumors

- Must be enrolled on COG-AREN03B2

PATIENT CHARACTERISTICS:

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

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

- No prior systemic chemotherapy or radiation therapy unless enrolled on COG-AREN0532
or COG-AREN0533 clinical trials and received prenephrectomy chemotherapy

- Patients with renal cell carcinoma who received prior chemotherapy for another
type of malignancy or non-malignant condition allowed

- Patients who received prior chemotherapy are not eligible for "window" therapy

- No more than 14 days since prior surgery or biopsy unless medically contraindicated
or pathological diagnosis requires special studies

- No concurrent aprepitant

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Event-free survival of patients with diffuse anaplastic Wilms' tumor (DAWT) treated with HU-1

Outcome Description:

An analysis plan based on the method of Woolson will be used to monitor outcome for these patients. O'Brien-Fleming boundary (truncated at 3 standard deviations) will be used.

Outcome Time Frame:

Up to 4 years

Safety Issue:

No

Principal Investigator

Jeffrey S. Dome, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Children's Research Institute

Authority:

United States: Food and Drug Administration

Study ID:

AREN0321

NCT ID:

NCT00335556

Start Date:

June 2006

Completion Date:

Related Keywords:

  • Kidney Cancer
  • stage I Wilms tumor
  • stage II Wilms tumor
  • stage III Wilms tumor
  • stage IV Wilms tumor
  • clear cell renal cell carcinoma
  • rhabdoid tumor of the kidney
  • stage I renal cell cancer
  • stage II renal cell cancer
  • stage III renal cell cancer
  • stage IV renal cell cancer
  • clear cell sarcoma of the kidney
  • childhood renal cell carcinoma
  • papillary renal cell carcinoma
  • Carcinoma, Renal Cell
  • Kidney Neoplasms

Name

Location

National Naval Medical CenterBethesda, Maryland  20889
Roswell Park Cancer InstituteBuffalo, New York  14263
Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
Mayo Clinic Cancer CenterRochester, Minnesota  55905
Cardinal Bernardin Cancer Center at Loyola University Medical CenterMaywood, Illinois  60153-5500
University of Chicago Cancer Research CenterChicago, Illinois  60637
Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201
Tripler Army Medical CenterHonolulu, Hawaii  96859-5000
Hurley Medical CenterFlint, Michigan  48503
Medical City Dallas HospitalDallas, Texas  75230
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
Presbyterian - St. Luke's Medical CenterDenver, Colorado  80218
Van Elslander Cancer Center at St. John Hospital and Medical CenterGrosse Pointe Woods, Michigan  48236
Bronson Methodist HospitalKalamazoo, Michigan  49007
Natalie Warren Bryant Cancer Center at St. Francis HospitalTulsa, Oklahoma  74136
Sanford Cancer Center at Sanford USD Medical CenterSioux Falls, South Dakota  57117-5039
Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838
University of Wisconsin Paul P. Carbone Comprehensive Cancer CenterMadison, Wisconsin  53792-6164
Marshfield Clinic - Marshfield CenterMarshfield, Wisconsin  54449
Newark Beth Israel Medical CenterNewark, New Jersey  07112
Holden Comprehensive Cancer Center at University of IowaIowa City, Iowa  52242-1002
UMASS Memorial Cancer Center - University CampusWorcester, Massachusetts  01605-2982
Ellis Fischel Cancer Center at University of Missouri - ColumbiaColumbia, Missouri  65203
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical CenterLebanon, New Hampshire  03756-0002
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570
CCOP - Scott and White HospitalTemple, Texas  76508
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410
Cancer Research Center of HawaiiHonolulu, Hawaii  96813
Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195
Children's Hospital of Orange CountyOrange, California  92668
Children's National Medical CenterWashington, District of Columbia  20010-2970
Children's Mercy HospitalKansas City, Missouri  64108
St. Joseph's Hospital and Medical CenterPaterson, New Jersey  07503
Children's Hospital and Regional Medical Center - SeattleSeattle, Washington  98105
Nemours Children's ClinicJacksonville, Florida  32207
All Children's HospitalSt. Petersburg, Florida  33701
Children's Memorial Hospital - ChicagoChicago, Illinois  60614
Saint Jude Midwest AffiliatePeoria, Illinois  61637
Children's Hospital of New OrleansNew Orleans, Louisiana  70118
Cardinal Glennon Children's HospitalSaint Louis, Missouri  63104
Schneider Children's HospitalNew Hyde Park, New York  11042
St. Christopher's Hospital for ChildrenPhiladelphia, Pennsylvania  19134-1095
St. Jude Children's Research HospitalMemphis, Tennessee  38105-2794
Driscoll Children's HospitalCorpus Christi, Texas  78466
Cook Children's Medical Center - Fort WorthFort Worth, Texas  76104
Inova Fairfax HospitalFalls Church, Virginia  22042-3300
Fletcher Allen Health Care - University Health Center CampusBurlington, Vermont  05401
Phoenix Children's HospitalPhoenix, Arizona  85016-7710
Southern California Permanente Medical GroupDowney, California  90242
Children's Hospital Central CaliforniaMadera, California  93638-8762
Kosair Children's HospitalLouisville, Kentucky  40202-3830
Brooklyn Hospital CenterBrooklyn, New York  11201
Palmetto Health South Carolina Cancer CenterColumbia, South Carolina  29203
East Tennessee Children's HospitalKnoxville, Tennessee  37901
Covenant Children's HospitalLubbock, Texas  79410
Children's Hospital of the King's DaughtersNorfolk, Virginia  23507
Midwest Children's Cancer Center at Children's Hospital of WisconsinMilwaukee, Wisconsin  53226
Arizona Cancer Center at University of Arizona Health Sciences CenterTucson, Arizona  85724
Arkansas Cancer Research Center at University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
Blumenthal Cancer Center at Carolinas Medical CenterCharlotte, North Carolina  28232-2861
Carol G. Simon Cancer Center at Morristown Memorial HospitalMorristown, New Jersey  07962
Loma Linda University Cancer Institute at Loma Linda University Medical CenterLoma Linda, California  92354
Jonathan Jaques Children's Cancer Center at Miller Children's HospitalLong Beach, California  90801
Kaiser Permanente Medical Center - OaklandSacramento, California  95825
Lee Cancer Care of Lee Memorial Health SystemFort Myers, Florida  33901
Broward General Medical Center Cancer CenterFt. Lauderdale, Florida  33316
Baptist-South Miami Regional Cancer ProgramMiami, Florida  33176
Nemours Children's Clinic - OrlandoOrlando, Florida  32806
Florida Hospital Cancer Institute at Florida Hospital OrlandoOrlando, Florida  32803-1273
St. Joseph's Cancer Institute at St. Joseph's HospitalTampa, Florida  33607
Kaplan Cancer Center at St. Mary's Medical CenterWest Palm Beach, Florida  33407
St. Vincent Indianapolis HospitalIndianapolis, Indiana  46260
Blank Children's HospitalDes Moines, Iowa  50309
Alvin and Lois Lapidus Cancer Institute at Sinai HospitalBaltimore, Maryland  21215
Breslin Cancer Center at Ingham Regional Medical CenterLansing, Michigan  48910
Hackensack University Medical Center Cancer CenterHackensack, New Jersey  07601
NYU Cancer Institute at New York University Medical CenterNew York, New York  10016
Stony Brook University Cancer CenterStony Brook, New York  11794-8174
SUNY Upstate Medical University HospitalSyracuse, New York  13210
Mission Hospitals - Memorial CampusAsheville, North Carolina  28801
Presbyterian Cancer Center at Presbyterian HospitalCharlotte, North Carolina  28233-3549
Wake Forest University Comprehensive Cancer CenterWinston-Salem, North Carolina  27157-1096
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Rainbow Babies and Children's HospitalCleveland, Ohio  44106-5000
Toledo HospitalToledo, Ohio  43606
Rhode Island Hospital Comprehensive Cancer CenterProvidence, Rhode Island  02903
Texas Tech University Health Sciences Center School of Medicine - AmarilloAmarillo, Texas  79106
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - DallasDallas, Texas  75390
Baylor University Medical Center - HoustonHouston, Texas  77030-2399
Methodist Children's Hospital of South TexasSan Antonio, Texas  78229-3993
Primary Children's Medical CenterSalt Lake City, Utah  84113-1100
Naval Medical Center - PortsmouthPortsmouth, Virginia  23708-2197
Providence Cancer Center at Sacred Heart Medical CenterSpokane, Washington  99220-2555
Edwards Comprehensive Cancer Center at Cabell Huntington HospitalHuntington, West Virginia  25701
James P. Wilmot Cancer Center at University of Rochester Medical CenterRochester, New York  14642
David C. Pratt Cancer Center at St. John's MercySt. Louis, Missouri  63141
UNMC Eppley Cancer Center at the University of Nebraska Medical CenterOmaha, Nebraska  68198-7680
Memorial Cancer Institute at Memorial Regional HospitalHollywood, Florida  33021
New York Weill Cornell Cancer Center at Cornell UniversityNew York, New York  10021
University of South Alabama Mitchell Cancer InstituteMobile, Alabama  36604
Childrens Hospital Los AngelesLos Angeles, California  90027
Children's Hospital and Research Center OaklandOakland, California  94609
Lucile Packard Children's Hospital at Stanford University Medical CenterPalo Alto, California  95798
Rady Children's Hospital - San DiegoSan Diego, California  92123-4282
UCSF Helen Diller Family Comprehensive Cancer CenterSan Francisco, California  94115
Alfred I. duPont Hospital for ChildrenWilmington, Delaware  19803
Lombardi Comprehensive Cancer Center at Georgetown University Medical CenterWashington, District of Columbia  20007
M.D. Anderson Cancer Center at OrlandoOrlando, Florida  32806
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston CampusAtlanta, Georgia  30322
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical CenterSavannah, Georgia  31403-3089
Mountain States Tumor Institute at St. Luke's Regional Medical CenterBoise, Idaho  83712-6297
University of Illinois Cancer CenterChicago, Illinois  60612-7243
Keyser Family Cancer Center at Advocate Hope Children's HospitalOak Lawn, Illinois  60453
Advocate Lutheran General Cancer Care CenterPark Ridge, Illinois  60068-1174
Simmons Cooper Cancer InstituteSpringfield, Illinois  62794-9677
Lucille P. Markey Cancer Center at University of KentuckyLexington, Kentucky  40536-0093
Tulane Cancer Center Office of Clinical ResearchAlexandria, Louisiana  71315-3198
CancerCare of Maine at Eastern Maine Medical CenterBangor, Maine  04401
Maine Children's Cancer Program at Barbara Bush Children's HospitalScarborough, Maine  04074-9308
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer InstituteBoston, Massachusetts  02115
C.S. Mott Children's Hospital at University of Michigan Medical CenterAnn Arbor, Michigan  48109-0286
Children's Hospitals and Clinics of Minnesota - MinneapolisMinneapolis, Minnesota  55404
University of Mississippi Cancer ClinicJackson, Mississippi  39216-4505
Siteman Cancer Center at Barnes-Jewish Hospital - Saint LouisSt. Louis, Missouri  63110
Children's HospitalOmaha, Nebraska  68114-4113
CCOP - Nevada Cancer Research FoundationLas Vegas, Nevada  89109-2306
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical SchoolNew Brunswick, New Jersey  08903
University of New Mexico Cancer CenterAlbuquerque, New Mexico  87131-5636
Herbert Irving Comprehensive Cancer Center at Columbia University Medical CenterNew York, New York  10032
Akron Children's HospitalAkron, Ohio  44308-1062
Nationwide Children's HospitalColumbus, Ohio  43205-2696
Dayton Children's - DaytonDayton, Ohio  45404-1815
Tod Children's HospitalYoungstown, Ohio  44501
Oklahoma University Cancer InstituteOklahoma City, Oklahoma  73104
Geisinger Cancer Institute at Geisinger HealthDanville, Pennsylvania  17822-0001
Penn State Children's HospitalHershey, Pennsylvania  17033-0850
Children's Hospital of Pittsburgh of UPMCPittsburgh, Pennsylvania  15213
Dell Children's Medical Center of Central TexasAustin, Texas  78723
Virginia Commonwealth University Massey Cancer CenterRichmond, Virginia  23298-0037
Carilion Medical Center for Children at Roanoke Community HospitalRoanoke, Virginia  24014
Madigan Army Medical Center - TacomaTacoma, Washington  98431
Mary Bridge Children's Hospital and Health Center - TacomaTacoma, Washington  98405
West Virginia University Health Sciences Center - CharlestonCharleston, West Virginia  25302
Riley's Children Cancer Center at Riley Hospital for ChildrenIndianapolis, Indiana  46202-5225
Massachusetts General HospitalBoston, Massachusetts  02114-2617
University of Miami Sylvester Comprehensive Cancer Center - MiamiMiami, Florida  33136
Leo W. Jenkins Cancer Center at ECU Medical SchoolGreenville, North Carolina  27834
Lehigh Valley Hospital - MuhlenbergBethlehem, Pennsylvania  18017
Duke Cancer InstituteDurham, North Carolina  27710
T.C. Thompson Children's HospitalChattanooga, Tennessee  37403
Connecticut Children's Medical CenterHartford, Connecticut  06106
Children's Hospital Colorado Center for Cancer and Blood DisordersAurora, Colorado  80045
Nemours Children's Clinic - PensacolaPensacola, Florida  32504
Helen DeVos Children's Hospital at Spectrum HealthGrand Rapids, Michigan  49503
Mercy Children's HospitalToledo, Ohio  43608
Legacy Emanuel Children's HospitalPortland, Oregon  97227
BI-LO Charities Children's Cancer CenterGreenville, South Carolina  29605
Children's Hospital of Alabama at University of Alabama at BirminghamBirmingham, Alabama  35233