Intensive Multi-Agent Therapy, Including Dose-Compressed Cycles of Ifosfamide/Etoposide (IE) and Vincristine/Doxorubicin/Cyclophosphamide (VDC) for Patients With High-Risk Rhabdomyosarcoma
OBJECTIVES:
Primary
- Improve the early disease control interval for patients with newly diagnosed,
high-risk, metastatic rhabdomyosarcoma or ectomesenchymoma using intensive,
interval-compression therapy (comprising vincristine, irinotecan hydrochloride,
ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, and dactinomycin)
that permits maximal early exposure to known effective agents.
- Determine the feasibility of concurrent irinotecan hydrochloride and radiotherapy in
these patients.
- Assess immediate- and short-term side effects of concurrent irinotecan hydrochloride
and radiotherapy in these patients.
Secondary
- Expand the available data for response to irinotecan hydrochloride and vincristine in
previously untreated patients with high-risk rhabdomyosarcoma.
- Evaluate, prospectively, and validate gene expression values with the intent to define
the best diagnostic predictors and more powerful prognostic classifiers.
OUTLINE: This is a prospective, nonrandomized, multicenter study. Patients are stratified
according to prognostic factors predictive of outcome (e.g. histology, bone/bone marrow
involvement, and number of metastatic sites).
Patients receive high-dose chemotherapy comprising vincristine IV over 1 minute on day 1 of
weeks 1-5, 7, 8, 11, 12, 15, 16, 20-24, 28, 29, 32, 33, 35, 38, 41-44, 47, 48, 50, and 51;
irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 1, 4, 20, 23, 47, and 50; and
ifosfamide IV over 1 hour and etoposide IV over 30-60 minutes on days 1-5 of weeks 9, 13,
17, 26, and 30. Patients also receive doxorubicin hydrochloride IV continuously over 24
hours on days 1 and 2 of weeks 7*, 11, 15, 28, and 32; cyclophosphamide IV over 30-60
minutes on day 1 of weeks 7, 11, 15, 28, 32, 35, 38, 41, and 44; and dactinomycin IV over
1-5 minutes on day 1 of weeks 35, 38, 41, and 44 in the absence of disease progression or
unacceptable toxicity. Patients also receive filgrastim (G-CSF) subcutaneously in weeks 7-9,
11-13, 15-17, 22, 26, 28-30, 32, 33, 35, 38, and 41-44 beginning 24-36 hours after the last
chemotherapy dose and continuing until blood counts recover.
NOTE: *Patients undergoing early radiotherapy for intracranial extension do not receive
doxorubicin in week 7.
Beginning at week 20 (or week 1 for patients with parameningeal tumors with intracranial
extension [or spinal cord compression] requiring emergency radiotherapy), patients also
undergo radiotherapy once a day, 5 days a week, for approximately 5½ weeks. Some patients
may also undergo second-look surgery.
After completion of study treatment, patients are followed periodically for ≥ 10 years.
PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Early disease control
Improve the early disease control interval for patients with newly diagnosed, high-risk, metastatic rhabdomyosarcoma or ectomesenchymoma using intensive, interval-compression therapy (comprising vincristine, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, and dactinomycin) that permits maximal early exposure to known effective agents.
2 years
No
Brenda Weigel, MD
Study Chair
Masonic Cancer Center, University of Minnesota
United States: Food and Drug Administration
ARST0431
NCT00354744
July 2006
Name | Location |
---|---|
Roswell Park Cancer Institute | Buffalo, New York 14263 |
Children's Hospital of Philadelphia | Philadelphia, Pennsylvania 19104 |
Mayo Clinic Cancer Center | Rochester, Minnesota 55905 |
Walter Reed Army Medical Center | Washington, District of Columbia 20307-5000 |
University of Chicago Cancer Research Center | Chicago, Illinois 60637 |
Barbara Ann Karmanos Cancer Institute | Detroit, Michigan 48201 |
University of Minnesota Cancer Center | Minneapolis, Minnesota 55455 |
Duke Comprehensive Cancer Center | Durham, North Carolina 27710 |
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 |
Midwest Children's Cancer Center | Milwaukee, Wisconsin 53226 |
CCOP - Kalamazoo | Kalamazoo, Michigan 49007-3731 |
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center | Farmington, Connecticut 06360-2875 |
Penn State Cancer Institute at Milton S. Hershey Medical Center | Hershey, Pennsylvania 17033-0850 |
Sanford Cancer Center at Sanford USD Medical Center | Sioux Falls, South Dakota 57117-5039 |
Vanderbilt-Ingram Cancer Center | Nashville, Tennessee 37232-6838 |
Marshfield Clinic - Marshfield Center | Marshfield, Wisconsin 54449 |
Newark Beth Israel Medical Center | Newark, New Jersey 07112 |
New York Medical College | Valhalla, New York 10595 |
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 |
Sutter Cancer Center | Sacramento, California 95816 |
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 of Pittsburgh | Pittsburgh, Pennsylvania 15213 |
Children's Hospital and Regional Medical Center - Seattle | Seattle, Washington 98105 |
University of California Davis Cancer Center | Sacramento, California 95817 |
Nemours Children's Clinic | Jacksonville, Florida 32207 |
Miami Children's Hospital | Miami, Florida 33155-4069 |
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 |
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute | Boston, Massachusetts 02115 |
Schneider Children's Hospital | New Hyde Park, New York 11042 |
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 |
Sunrise Hospital and Medical Center | Las Vegas, Nevada 89109-2306 |
Children's Medical Center - Dayton | Dayton, Ohio 45404 |
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 |
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 |
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center | Kansas City, Kansas 66160-7353 |
Blumenthal Cancer Center at Carolinas Medical Center | Charlotte, North Carolina 28232-2861 |
Overlook Hospital | Summit, New Jersey 07902-0220 |
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 |
University of Florida Shands Cancer Center | Gainesville, Florida 32610-0232 |
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 |
Sacred Heart Cancer Center at Sacred Heart Hospital | Pensacola, Florida 32504 |
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 |
Winship Cancer Institute of Emory University | Atlanta, Georgia 30322 |
Advocate Christ Medical Center | Oak Lawn, Illinois 60453 |
St. Vincent Indianapolis Hospital | Indianapolis, Indiana 46260 |
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital | Baltimore, Maryland 21215 |
Floating Hospital for Children at Tufts - New England Medical Center | Boston, Massachusetts 02111 |
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 |
Medical University of Ohio Cancer Center | Toledo, Ohio 43614 |
Toledo Hospital | Toledo, Ohio 43606 |
Hollings Cancer Center at Medical University of South Carolina | Charleston, South Carolina 29425 |
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 |
Providence Cancer Center at Sacred Heart Medical Center | Spokane, Washington 99220-2555 |
James P. Wilmot Cancer Center at University of Rochester Medical Center | Rochester, New York 14642 |
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 |
Childrens Hospital Los Angeles | Los Angeles, California 90027 |
Children's Hospital and Research Center Oakland | Oakland, California 94609 |
Rady Children's Hospital - San Diego | San Diego, California 92123-4282 |
UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco, California 94115 |
Children's Hospital Center for Cancer and Blood Disorders | Aurora, Colorado 80045 |
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 |
MBCCOP - Medical College of Georgia Cancer Center | Augusta, Georgia 30912-3730 |
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center | Savannah, Georgia 31403-3089 |
University of Illinois Cancer Center | Chicago, Illinois 60612-7243 |
Advocate Lutheran General Cancer Care Center | Park Ridge, Illinois 60068-1174 |
Simmons Cooper Cancer Institute | Springfield, Illinois 62794-9677 |
Indiana University Melvin and Bren Simon Cancer Center | Indianapolis, Indiana 46202-5289 |
Lucille P. Markey Cancer Center at University of Kentucky | Lexington, Kentucky 40536-0093 |
Tulane Cancer Center Office of Clinical Research | Alexandria, Louisiana 71315-3198 |
C.S. Mott Children's Hospital at University of Michigan Medical Center | Ann Arbor, Michigan 48109-0286 |
Butterworth Hospital at Spectrum Health | Grand Rapids, Michigan 49503-2560 |
Children's Hospitals and Clinics of Minnesota - Minneapolis | Minneapolis, Minnesota 55404 |
University of Mississippi Cancer Clinic | Jackson, Mississippi 39216-4505 |
Children's Hospital | Omaha, Nebraska 68114-4113 |
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 |
Albany Medical Center Hospital | Albany, New York 12208-3419 |
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 |
Oklahoma University Cancer Institute | Oklahoma City, Oklahoma 73104 |
Geisinger Cancer Institute at Geisinger Health | Danville, Pennsylvania 17822-0001 |
Dell Children's Medical Center of Central Texas | Austin, Texas 78723 |
M. D. Anderson Cancer Center at University of Texas | Houston, Texas 77030-4009 |
Carilion Medical Center for Children at Roanoke Community Hospital | Roanoke, Virginia 24014 |
Mary Bridge Children's Hospital and Health Center - Tacoma | Tacoma, Washington 98405 |
West Virginia University Health Sciences Center - Charleston | Charleston, West Virginia 25302 |
Massachusetts General Hospital | Boston, Massachusetts 02114-2617 |
Stanford Cancer Center | Stanford, California 94305-5824 |
Lehigh Valley Hospital - Muhlenberg | Bethlehem, Pennsylvania 18017 |
Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham | Birmingham, Alabama 35294 |
Greenville Hospital Cancer Center | Greenville, South Carolina 29605 |
T.C. Thompson Children's Hospital | Chattanooga, Tennessee 37403 |
Siteman Cancer Center at Barnes-Jewish St. Peters Hospital - Saint Louis | St Louis, Missouri 63110 |
Oregon Health and Science University Cancer Institute | Portland, Oregon 97239-3098 |