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Intensive Multi-Agent Therapy, Including Dose-Compressed Cycles of Ifosfamide/Etoposide (IE) and Vincristine/Doxorubicin/Cyclophosphamide (VDC) for Patients With High-Risk Rhabdomyosarcoma

Phase 3
49 Years
Not Enrolling

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Trial Information

Intensive Multi-Agent Therapy, Including Dose-Compressed Cycles of Ifosfamide/Etoposide (IE) and Vincristine/Doxorubicin/Cyclophosphamide (VDC) for Patients With High-Risk Rhabdomyosarcoma



- 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.


- 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.

Inclusion Criteria


- Histologically confirmed high-risk rhabdomyosarcoma or ectomesenchymoma

- Prior enrollment on COG-D9902 to confirm local histological diagnosis required

- Tissue must be submitted for pathologic review within 2 days of patient
registration on COG-D9902

- Newly diagnosed disease

- Metastatic disease (stage IV, clinical group IV)

- Has undergone initial surgical procedure (including biopsy) that provided the
definitive diagnosis within the past 42 days

- Parameningeal and paraspinal tumors allowed

- Patients with parameningeal (without intracranial extension [ICE]) and
paraspinal tumors should begin study chemotherapy at week 1 and radiotherapy at
week 20

- Patients with evidence of ICE, as defined by contrast MRI showing that primary tumor
touches, displaces, invades, distorts, or otherwise causes a signal abnormality of
the dura in contiguity to the primary site in brain or spinal cord, are eligible

- ICE is presumed to exist if the cerebrospinal fluid cytopathology is positive
for tumor at diagnosis

- Patients requiring emergency radiotherapy are eligible

- Patients requiring emergency radiotherapy (for intracranial extension or spinal
cord impingement) should begin study chemotherapy at week 1 (irinotecan
hydrochloride and vincristine) concurrently with radiation therapy


- ECOG or Zubrod performance status (PS) 0-2 (Lansky PS 50-100% for patients < 10 years
of age and Karnofsky PS 50-100% for patients ≥ 10 years of age)

- Absolute neutrophil count ≥ 750/mm³*

- Platelet count ≥ 75,000/mm³*

- Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min (≥ 40
mL/min for infants < 1 year of age)

- Patients with urinary tract obstruction by tumor must meet the renal function
criteria listed above AND must have unimpeded urinary flow established via
decompression of the obstructed portion of the urinary tract

- SGPT < 2.5 times normal

- Bilirubin < 1.5 mg/dL

- Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by MUGA

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during study and for ≥ 1 month
after study completion

- No evidence of uncontrolled infection

- Able to undergo radiotherapy NOTE: *Abnormal blood counts allowed if there is bone
marrow biopsy or aspirate proven bone marrow involvement by rhabdomyosarcoma


- No prior chemotherapy except steroids

- No prior radiotherapy

- No concurrent aprepitant during ifosfamide or doxorubicin hydrochloride chemotherapy

- No concurrent dexrazoxane

- No concurrent sargramostim (GM-CSF) or pegfilgrastim

Type of Study:


Study Design:

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

Outcome Measure:

Early disease control

Outcome Description:

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.

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Brenda Weigel, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Masonic Cancer Center, University of Minnesota


United States: Food and Drug Administration

Study ID:




Start Date:

July 2006

Completion Date:

Related Keywords:

  • Sarcoma
  • adult rhabdomyosarcoma
  • previously untreated childhood rhabdomyosarcoma
  • adult malignant mesenchymoma
  • childhood malignant mesenchymoma
  • metastatic childhood soft tissue sarcoma
  • stage IV adult soft tissue sarcoma
  • Rhabdomyosarcoma
  • Sarcoma



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