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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
N/A
49 Years
Not Enrolling
Both
Sarcoma

Thank you

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


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.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- 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

PATIENT CHARACTERISTICS:

- 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

PRIOR CONCURRENT THERAPY:

- 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:

Interventional

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:

No

Principal Investigator

Brenda Weigel, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Masonic Cancer Center, University of Minnesota

Authority:

United States: Food and Drug Administration

Study ID:

ARST0431

NCT ID:

NCT00354744

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

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
Mayo Clinic Cancer CenterRochester, Minnesota  55905
Walter Reed Army Medical CenterWashington, District of Columbia  20307-5000
University of Chicago Cancer Research CenterChicago, Illinois  60637
Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201
University of Minnesota Cancer CenterMinneapolis, Minnesota  55455
Duke Comprehensive Cancer CenterDurham, North Carolina  27710
Hurley Medical CenterFlint, Michigan  48503
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
CCOP - KalamazooKalamazoo, Michigan  49007-3731
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health CenterFarmington, Connecticut  06360-2875
Penn State Cancer Institute at Milton S. Hershey Medical CenterHershey, Pennsylvania  17033-0850
Sanford Cancer Center at Sanford USD Medical CenterSioux Falls, South Dakota  57117-5039
Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838
Marshfield Clinic - Marshfield CenterMarshfield, Wisconsin  54449
Newark Beth Israel Medical CenterNewark, New Jersey  07112
New York Medical CollegeValhalla, New York  10595
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
Sutter Cancer CenterSacramento, California  95816
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 of PittsburghPittsburgh, Pennsylvania  15213
Children's Hospital and Regional Medical Center - SeattleSeattle, Washington  98105
University of California Davis Cancer CenterSacramento, California  95817
Nemours Children's ClinicJacksonville, Florida  32207
Miami Children's HospitalMiami, Florida  33155-4069
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
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer InstituteBoston, Massachusetts  02115
Schneider Children's HospitalNew Hyde Park, New York  11042
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
Sunrise Hospital and Medical CenterLas Vegas, Nevada  89109-2306
Children's Medical Center - DaytonDayton, Ohio  45404
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
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
Kansas Masonic Cancer Research Institute at the University of Kansas Medical CenterKansas City, Kansas  66160-7353
Blumenthal Cancer Center at Carolinas Medical CenterCharlotte, North Carolina  28232-2861
Overlook HospitalSummit, New Jersey  07902-0220
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
University of Florida Shands Cancer CenterGainesville, Florida  32610-0232
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
Sacred Heart Cancer Center at Sacred Heart HospitalPensacola, Florida  32504
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
Winship Cancer Institute of Emory UniversityAtlanta, Georgia  30322
Advocate Christ Medical CenterOak Lawn, Illinois  60453
St. Vincent Indianapolis HospitalIndianapolis, Indiana  46260
Alvin and Lois Lapidus Cancer Institute at Sinai HospitalBaltimore, Maryland  21215
Floating Hospital for Children at Tufts - New England Medical CenterBoston, Massachusetts  02111
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
Medical University of Ohio Cancer CenterToledo, Ohio  43614
Toledo HospitalToledo, Ohio  43606
Hollings Cancer Center at Medical University of South CarolinaCharleston, South Carolina  29425
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
Providence Cancer Center at Sacred Heart Medical CenterSpokane, Washington  99220-2555
James P. Wilmot Cancer Center at University of Rochester Medical CenterRochester, New York  14642
UNMC Eppley Cancer Center at the University of Nebraska Medical CenterOmaha, Nebraska  68198-7680
Memorial Cancer Institute at Memorial Regional HospitalHollywood, Florida  33021
Childrens Hospital Los AngelesLos Angeles, California  90027
Children's Hospital and Research Center OaklandOakland, California  94609
Rady Children's Hospital - San DiegoSan Diego, California  92123-4282
UCSF Helen Diller Family Comprehensive Cancer CenterSan Francisco, California  94115
Children's Hospital Center for Cancer and Blood DisordersAurora, Colorado  80045
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
MBCCOP - Medical College of Georgia Cancer CenterAugusta, Georgia  30912-3730
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical CenterSavannah, Georgia  31403-3089
University of Illinois Cancer CenterChicago, Illinois  60612-7243
Advocate Lutheran General Cancer Care CenterPark Ridge, Illinois  60068-1174
Simmons Cooper Cancer InstituteSpringfield, Illinois  62794-9677
Indiana University Melvin and Bren Simon Cancer CenterIndianapolis, Indiana  46202-5289
Lucille P. Markey Cancer Center at University of KentuckyLexington, Kentucky  40536-0093
Tulane Cancer Center Office of Clinical ResearchAlexandria, Louisiana  71315-3198
C.S. Mott Children's Hospital at University of Michigan Medical CenterAnn Arbor, Michigan  48109-0286
Butterworth Hospital at Spectrum HealthGrand Rapids, Michigan  49503-2560
Children's Hospitals and Clinics of Minnesota - MinneapolisMinneapolis, Minnesota  55404
University of Mississippi Cancer ClinicJackson, Mississippi  39216-4505
Children's HospitalOmaha, Nebraska  68114-4113
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
Albany Medical Center HospitalAlbany, New York  12208-3419
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
Oklahoma University Cancer InstituteOklahoma City, Oklahoma  73104
Geisinger Cancer Institute at Geisinger HealthDanville, Pennsylvania  17822-0001
Dell Children's Medical Center of Central TexasAustin, Texas  78723
M. D. Anderson Cancer Center at University of TexasHouston, Texas  77030-4009
Carilion Medical Center for Children at Roanoke Community HospitalRoanoke, Virginia  24014
Mary Bridge Children's Hospital and Health Center - TacomaTacoma, Washington  98405
West Virginia University Health Sciences Center - CharlestonCharleston, West Virginia  25302
Massachusetts General HospitalBoston, Massachusetts  02114-2617
Stanford Cancer CenterStanford, California  94305-5824
Lehigh Valley Hospital - MuhlenbergBethlehem, Pennsylvania  18017
Lurleen Wallace Comprehensive Cancer at University of Alabama - BirminghamBirmingham, Alabama  35294
Greenville Hospital Cancer CenterGreenville, South Carolina  29605
T.C. Thompson Children's HospitalChattanooga, Tennessee  37403
Siteman Cancer Center at Barnes-Jewish St. Peters Hospital - Saint LouisSt Louis, Missouri  63110
Oregon Health and Science University Cancer InstitutePortland, Oregon  97239-3098