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.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Event-free survival of patients with diffuse anaplastic Wilms' tumor (DAWT) treated with HU-1
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.
Up to 4 years
No
Jeffrey S. Dome, MD
Study Chair
Children's Research Institute
United States: Food and Drug Administration
AREN0321
NCT00335556
June 2006
Name | Location |
---|---|
National Naval Medical Center | Bethesda, Maryland 20889 |
Roswell Park Cancer Institute | Buffalo, New York 14263 |
Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
Children's Hospital of Philadelphia | Philadelphia, Pennsylvania 19104 |
Mayo Clinic Cancer Center | Rochester, Minnesota 55905 |
Cardinal Bernardin Cancer Center at Loyola University Medical Center | Maywood, Illinois 60153-5500 |
University of Chicago Cancer Research Center | Chicago, Illinois 60637 |
Barbara Ann Karmanos Cancer Institute | Detroit, Michigan 48201 |
Tripler Army Medical Center | Honolulu, Hawaii 96859-5000 |
Hurley Medical Center | Flint, Michigan 48503 |
Medical City Dallas Hospital | Dallas, Texas 75230 |
University of Texas Health Science Center at San Antonio | San Antonio, Texas 78284-7811 |
Presbyterian - St. Luke's Medical Center | Denver, Colorado 80218 |
Van Elslander Cancer Center at St. John Hospital and Medical Center | Grosse Pointe Woods, Michigan 48236 |
Bronson Methodist Hospital | Kalamazoo, Michigan 49007 |
Natalie Warren Bryant Cancer Center at St. Francis Hospital | Tulsa, Oklahoma 74136 |
Sanford Cancer Center at Sanford USD Medical Center | Sioux Falls, South Dakota 57117-5039 |
Vanderbilt-Ingram Cancer Center | Nashville, Tennessee 37232-6838 |
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center | Madison, Wisconsin 53792-6164 |
Marshfield Clinic - Marshfield Center | Marshfield, Wisconsin 54449 |
Newark Beth Israel Medical Center | Newark, New Jersey 07112 |
Holden Comprehensive Cancer Center at University of Iowa | Iowa City, Iowa 52242-1002 |
UMASS Memorial Cancer Center - University Campus | Worcester, Massachusetts 01605-2982 |
Ellis Fischel Cancer Center at University of Missouri - Columbia | Columbia, Missouri 65203 |
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center | Lebanon, New Hampshire 03756-0002 |
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill | Chapel Hill, North Carolina 27599-7570 |
CCOP - Scott and White Hospital | Temple, Texas 76508 |
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |
Cancer Research Center of Hawaii | Honolulu, Hawaii 96813 |
Cleveland Clinic Taussig Cancer Center | Cleveland, Ohio 44195 |
Children's Hospital of Orange County | Orange, California 92668 |
Children's National Medical Center | Washington, District of Columbia 20010-2970 |
Children's Mercy Hospital | Kansas City, Missouri 64108 |
St. Joseph's Hospital and Medical Center | Paterson, New Jersey 07503 |
Children's Hospital and Regional Medical Center - Seattle | Seattle, Washington 98105 |
Nemours Children's Clinic | Jacksonville, Florida 32207 |
All Children's Hospital | St. Petersburg, Florida 33701 |
Children's Memorial Hospital - Chicago | Chicago, Illinois 60614 |
Saint Jude Midwest Affiliate | Peoria, Illinois 61637 |
Children's Hospital of New Orleans | New Orleans, Louisiana 70118 |
Cardinal Glennon Children's Hospital | Saint Louis, Missouri 63104 |
Schneider Children's Hospital | New Hyde Park, New York 11042 |
St. Christopher's Hospital for Children | Philadelphia, Pennsylvania 19134-1095 |
St. Jude Children's Research Hospital | Memphis, Tennessee 38105-2794 |
Driscoll Children's Hospital | Corpus Christi, Texas 78466 |
Cook Children's Medical Center - Fort Worth | Fort Worth, Texas 76104 |
Inova Fairfax Hospital | Falls Church, Virginia 22042-3300 |
Fletcher Allen Health Care - University Health Center Campus | Burlington, Vermont 05401 |
Phoenix Children's Hospital | Phoenix, Arizona 85016-7710 |
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 |
Palmetto Health South Carolina Cancer Center | Columbia, South Carolina 29203 |
East Tennessee Children's Hospital | Knoxville, Tennessee 37901 |
Covenant Children's Hospital | Lubbock, Texas 79410 |
Children's Hospital of the King's Daughters | Norfolk, Virginia 23507 |
Midwest Children's Cancer Center at Children's Hospital of Wisconsin | Milwaukee, Wisconsin 53226 |
Arizona Cancer Center at University of Arizona Health Sciences Center | Tucson, Arizona 85724 |
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences | Little Rock, Arkansas 72205 |
Blumenthal Cancer Center at Carolinas Medical Center | Charlotte, North Carolina 28232-2861 |
Carol G. Simon Cancer Center at Morristown Memorial Hospital | Morristown, New Jersey 07962 |
Loma Linda University Cancer Institute at Loma Linda University Medical Center | Loma Linda, California 92354 |
Jonathan Jaques Children's Cancer Center at Miller Children's Hospital | Long Beach, California 90801 |
Kaiser Permanente Medical Center - Oakland | Sacramento, California 95825 |
Lee Cancer Care of Lee Memorial Health System | Fort Myers, Florida 33901 |
Broward General Medical Center Cancer Center | Ft. Lauderdale, Florida 33316 |
Baptist-South Miami Regional Cancer Program | Miami, Florida 33176 |
Nemours Children's Clinic - Orlando | Orlando, Florida 32806 |
Florida Hospital Cancer Institute at Florida Hospital Orlando | Orlando, Florida 32803-1273 |
St. Joseph's Cancer Institute at St. Joseph's Hospital | Tampa, Florida 33607 |
Kaplan Cancer Center at St. Mary's Medical Center | West Palm Beach, Florida 33407 |
St. Vincent Indianapolis Hospital | Indianapolis, Indiana 46260 |
Blank Children's Hospital | Des Moines, Iowa 50309 |
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital | Baltimore, Maryland 21215 |
Breslin Cancer Center at Ingham Regional Medical Center | Lansing, Michigan 48910 |
Hackensack University Medical Center Cancer Center | Hackensack, New Jersey 07601 |
NYU Cancer Institute at New York University Medical Center | New York, New York 10016 |
Stony Brook University Cancer Center | Stony Brook, New York 11794-8174 |
SUNY Upstate Medical University Hospital | Syracuse, New York 13210 |
Mission Hospitals - Memorial Campus | Asheville, North Carolina 28801 |
Presbyterian Cancer Center at Presbyterian Hospital | Charlotte, North Carolina 28233-3549 |
Wake Forest University Comprehensive Cancer Center | Winston-Salem, North Carolina 27157-1096 |
Cincinnati Children's Hospital Medical Center | Cincinnati, Ohio 45229-3039 |
Rainbow Babies and Children's Hospital | Cleveland, Ohio 44106-5000 |
Toledo Hospital | Toledo, Ohio 43606 |
Rhode Island Hospital Comprehensive Cancer Center | Providence, Rhode Island 02903 |
Texas Tech University Health Sciences Center School of Medicine - Amarillo | Amarillo, Texas 79106 |
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas | Dallas, Texas 75390 |
Baylor University Medical Center - Houston | Houston, Texas 77030-2399 |
Methodist Children's Hospital of South Texas | San Antonio, Texas 78229-3993 |
Primary Children's Medical Center | Salt Lake City, Utah 84113-1100 |
Naval Medical Center - Portsmouth | Portsmouth, Virginia 23708-2197 |
Providence Cancer Center at Sacred Heart Medical Center | Spokane, Washington 99220-2555 |
Edwards Comprehensive Cancer Center at Cabell Huntington Hospital | Huntington, West Virginia 25701 |
James P. Wilmot Cancer Center at University of Rochester Medical Center | Rochester, New York 14642 |
David C. Pratt Cancer Center at St. John's Mercy | St. Louis, Missouri 63141 |
UNMC Eppley Cancer Center at the University of Nebraska Medical Center | Omaha, Nebraska 68198-7680 |
Memorial Cancer Institute at Memorial Regional Hospital | Hollywood, Florida 33021 |
New York Weill Cornell Cancer Center at Cornell University | New York, New York 10021 |
University of South Alabama Mitchell Cancer Institute | Mobile, Alabama 36604 |
Childrens Hospital Los Angeles | Los Angeles, California 90027 |
Children's Hospital and Research Center Oakland | Oakland, California 94609 |
Lucile Packard Children's Hospital at Stanford University Medical Center | Palo Alto, California 95798 |
Rady Children's Hospital - San Diego | San Diego, California 92123-4282 |
UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco, California 94115 |
Alfred I. duPont Hospital for Children | Wilmington, Delaware 19803 |
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center | Washington, District of Columbia 20007 |
M.D. Anderson Cancer Center at Orlando | Orlando, Florida 32806 |
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus | Atlanta, Georgia 30322 |
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center | Savannah, Georgia 31403-3089 |
Mountain States Tumor Institute at St. Luke's Regional Medical Center | Boise, Idaho 83712-6297 |
University of Illinois Cancer Center | Chicago, Illinois 60612-7243 |
Keyser Family Cancer Center at Advocate Hope Children's Hospital | Oak Lawn, Illinois 60453 |
Advocate Lutheran General Cancer Care Center | Park Ridge, Illinois 60068-1174 |
Simmons Cooper Cancer Institute | Springfield, Illinois 62794-9677 |
Lucille P. Markey Cancer Center at University of Kentucky | Lexington, Kentucky 40536-0093 |
Tulane Cancer Center Office of Clinical Research | Alexandria, Louisiana 71315-3198 |
CancerCare of Maine at Eastern Maine Medical Center | Bangor, Maine 04401 |
Maine Children's Cancer Program at Barbara Bush Children's Hospital | Scarborough, Maine 04074-9308 |
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute | Boston, Massachusetts 02115 |
C.S. Mott Children's Hospital at University of Michigan Medical Center | Ann Arbor, Michigan 48109-0286 |
Children's Hospitals and Clinics of Minnesota - Minneapolis | Minneapolis, Minnesota 55404 |
University of Mississippi Cancer Clinic | Jackson, Mississippi 39216-4505 |
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis | St. Louis, Missouri 63110 |
Children's Hospital | Omaha, Nebraska 68114-4113 |
CCOP - Nevada Cancer Research Foundation | Las Vegas, Nevada 89109-2306 |
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School | New Brunswick, New Jersey 08903 |
University of New Mexico Cancer Center | Albuquerque, New Mexico 87131-5636 |
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center | New York, New York 10032 |
Akron Children's Hospital | Akron, Ohio 44308-1062 |
Nationwide Children's Hospital | Columbus, Ohio 43205-2696 |
Dayton Children's - Dayton | Dayton, Ohio 45404-1815 |
Tod Children's Hospital | Youngstown, Ohio 44501 |
Oklahoma University Cancer Institute | Oklahoma City, Oklahoma 73104 |
Geisinger Cancer Institute at Geisinger Health | Danville, Pennsylvania 17822-0001 |
Penn State Children's Hospital | Hershey, Pennsylvania 17033-0850 |
Children's Hospital of Pittsburgh of UPMC | Pittsburgh, Pennsylvania 15213 |
Dell Children's Medical Center of Central Texas | Austin, Texas 78723 |
Virginia Commonwealth University Massey Cancer Center | Richmond, Virginia 23298-0037 |
Carilion Medical Center for Children at Roanoke Community Hospital | Roanoke, Virginia 24014 |
Madigan Army Medical Center - Tacoma | Tacoma, Washington 98431 |
Mary Bridge Children's Hospital and Health Center - Tacoma | Tacoma, Washington 98405 |
West Virginia University Health Sciences Center - Charleston | Charleston, West Virginia 25302 |
Riley's Children Cancer Center at Riley Hospital for Children | Indianapolis, Indiana 46202-5225 |
Massachusetts General Hospital | Boston, Massachusetts 02114-2617 |
University of Miami Sylvester Comprehensive Cancer Center - Miami | Miami, Florida 33136 |
Leo W. Jenkins Cancer Center at ECU Medical School | Greenville, North Carolina 27834 |
Lehigh Valley Hospital - Muhlenberg | Bethlehem, Pennsylvania 18017 |
Duke Cancer Institute | Durham, North Carolina 27710 |
T.C. Thompson Children's Hospital | Chattanooga, Tennessee 37403 |
Connecticut Children's Medical Center | Hartford, Connecticut 06106 |
Children's Hospital Colorado Center for Cancer and Blood Disorders | Aurora, Colorado 80045 |
Nemours Children's Clinic - Pensacola | Pensacola, Florida 32504 |
Helen DeVos Children's Hospital at Spectrum Health | Grand Rapids, Michigan 49503 |
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 |
Children's Hospital of Alabama at University of Alabama at Birmingham | Birmingham, Alabama 35233 |