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Randomized Study of Vincristine, Dactinomycin and Cyclophosphamide (VAC) Versus VAC Alternating With Vincristine and Irinotecan (VI) for Patients With Intermediate-Risk Rhabdomyosarcoma (RMS)


Phase 3
N/A
50 Years
Open (Enrolling)
Both
Adult Malignant Mesenchymoma, Adult Rhabdomyosarcoma, Alveolar Childhood Rhabdomyosarcoma, Childhood Malignant Mesenchymoma, Embryonal Childhood Rhabdomyosarcoma, Embryonal-botryoid Childhood Rhabdomyosarcoma, Nonmetastatic Childhood Soft Tissue Sarcoma, Previously Untreated Childhood Rhabdomyosarcoma, Stage I Adult Soft Tissue Sarcoma, Stage II Adult Soft Tissue Sarcoma, Stage III Adult Soft Tissue Sarcoma

Thank you

Trial Information

Randomized Study of Vincristine, Dactinomycin and Cyclophosphamide (VAC) Versus VAC Alternating With Vincristine and Irinotecan (VI) for Patients With Intermediate-Risk Rhabdomyosarcoma (RMS)


PRIMARY OBJECTIVES:

I. Compare the early response rates in patients with intermediate-risk rhabdomyosarcoma
(RMS) treated with vincristine, dactinomycin, and cyclophosphamide (VAC) vs VAC alternating
with vincristine and irinotecan hydrochloride (VI) in combination with radiotherapy.

II. Compare failure-free survival (FFS) and overall survival of patients treated with these
regimens.

SECONDARY OBJECTIVES:

I. Compare FFS, local control, and survival of patients with intermediate-risk RMS treated
with VAC and early (week 4) radiotherapy vs delayed (week 10) radiotherapy, using data from
IRS-IV for historic comparison.

II. Compare the acute and late effects of VAC vs VAC alternating with VI, including the
toxicity associated with concurrent VI and radiotherapy.

III. Compare the acute and late effects of VAC as delivered on this study to that
administered on COG-D9803.

IV. Correlate change in fludeoxyglucose F^18 positron emission tomography (FDG-PET) maximum
standard uptake value from week 1 to week 4 and 15 with FFS.

V. Correlate UGT1A1 genotype with VI toxicity in patients receiving VAC alternating with VI.

VI. Correlate CYP2B6, CYP2C9, and GSTA1 genotypes with VAC toxicity. VII. Prospectively
evaluate and validate gene expression values with the intent to define the best diagnostic
predictors and more powerful prognostic classifiers.

OUTLINE: This is a prospective, historic control, randomized, multicenter study. Patients
are stratified according to histology, disease stage, and clinical group (group III, stage 2
or 3 embryonal rhabdomyosarcoma [RMS] vs group I, stage 1 alveolar RMS vs group II or III,
stage 2 or 3 alveolar RMS). Patients are randomized to 1 of 2 treatment arms within 42 days
of initial surgery or biopsy.

ARM I (VAC): Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on
day 1 of weeks 1-13, 16, 19-25, 28, 31-37, and 40; dactinomycin IV over 1-5 minutes on day 1
of weeks 1, 4, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40; and cyclophosphamide IV over 1
hour on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40.

ARM II (VAC/VI): Patients receive VAC chemotherapy alternating with VI chemotherapy
comprising vincristine IV over 1 minute on day 1 of weeks 1-13,16, 17, 19, 20, 22-26, 28,
31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1,13, 22, 28, 34,
and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and
irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and
37.

In both arms, treatment continues in the absence of disease progression or unacceptable
toxicity. Patients* in both arms also undergo radiotherapy 5 days a week for 4-6 weeks
beginning in week 4 (except patients with alveolar RMS rendered group I by amputation OR
patients needing week 1 emergency radiotherapy for symptomatic spinal cord compression).

NOTE: *Individualized local control plan that deviates from protocol-mandated radiotherapy
allowed for patients ≤ 24 months of age.

After completion of study treatment, patients are followed periodically for ≥ 10 years.


Inclusion Criteria:



- Histologically or cytologically confirmed rhabdomyosarcoma (RMS)

- Must be concurrently enrolled on COG-D9902 to confirm local histologic diagnosis

- Intermediate-risk disease, defined by 1 of the following surgicopathological and
staging criteria:

- Group III, stage 2 or 3 embryonal, botryoid, or spindle cell RMS

- Group III, stage 2 or 3 ectomesenchymoma

- Group I-III, stage 1-3 alveolar RMS

- Newly diagnosed disease

- Staging ipsilateral retroperitoneal lymph node dissection (SIRLND) required for
patients ≥ 10 years of age with paratesticular tumors and for patients < 10 years
with clinically or radiographically involved lymph nodes

- Patients with extensive lymph node involvement, defined as ≥ 2 lymph nodes > 2
cm in dimension, identified by imaging studies, are not required to undergo
SIRLND

- Regional lymph node sampling or sentinel lymph node procedure is required for
histologic evaluation in patients with extremity tumors

- Has undergone initial surgery or biopsy within the past 42 days

- Must be able to undergo radiotherapy

- ECOG performance status (PS) 0-2 (Karnofsky PS 50-100% [≥ 16 years of age] or Lansky
PS 50-100% [< 16 years of age])

- Absolute neutrophil count ≥ 750/mm^3

- Platelet count ≥ 75,000/mm^3 (transfusion independent)

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- 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 have unimpeded urinary flow
established via decompression of the obstructed portion of the urinary tract

- Not pregnant or nursing

- Negative pregnancy test

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

- No evidence of uncontrolled infection

- No prior chemotherapy* (excluding steroids)

- No prior radiotherapy*

- No concurrent aprepitant during treatment with cyclophosphamide

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Comparison of failure-free survival (FFS) between the two treatment groups

Outcome Description:

A 1-sided alpha level was chosen as primary interest is in detecting an improvement in FFS under the more intensive therapy. The FFS distributions will be estimated using the Kaplan-Meier method and will be compared between the therapy groups using a log-rank test.

Outcome Time Frame:

Up to 7 years

Safety Issue:

No

Principal Investigator

Douglas Hawkins

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group

Authority:

United States: Institutional Review Board

Study ID:

ARST0531

NCT ID:

NCT00354835

Start Date:

December 2006

Completion Date:

Related Keywords:

  • Adult Malignant Mesenchymoma
  • Adult Rhabdomyosarcoma
  • Alveolar Childhood Rhabdomyosarcoma
  • Childhood Malignant Mesenchymoma
  • Embryonal Childhood Rhabdomyosarcoma
  • Embryonal-botryoid Childhood Rhabdomyosarcoma
  • Nonmetastatic Childhood Soft Tissue Sarcoma
  • Previously Untreated Childhood Rhabdomyosarcoma
  • Stage I Adult Soft Tissue Sarcoma
  • Stage II Adult Soft Tissue Sarcoma
  • Stage III Adult Soft Tissue Sarcoma
  • Mesenchymoma
  • Rhabdomyosarcoma
  • Rhabdomyosarcoma, Embryonal
  • Sarcoma
  • Liver Neoplasms

Name

Location

Baylor College of MedicineHouston, Texas  77030
Johns Hopkins UniversityBaltimore, Maryland  21205
Cleveland Clinic FoundationCleveland, Ohio  44195
Roswell Park Cancer InstituteBuffalo, New York  14263
Mayo ClinicRochester, Minnesota  55905
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
University of Mississippi Medical CenterJackson, Mississippi  39216-4505
Washington University School of MedicineSaint Louis, Missouri  63110
Medical University of South CarolinaCharleston, South Carolina  29425-0721
Hurley Medical CenterFlint, Michigan  48503
Rhode Island HospitalProvidence, Rhode Island  02903
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
Sinai Hospital of BaltimoreBaltimore, Maryland  21225
Bronson Methodist HospitalKalamazoo, Michigan  49007
Geisinger Medical CenterDanville, Pennsylvania  17822-0001
Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838
Loyola University Medical CenterMaywood, Illinois  60153
Massachusetts General Hospital Cancer CenterBoston, Massachusetts  02114
Morristown Memorial HospitalMorristown, New Jersey  07962-1956
Marshfield ClinicMarshfield, Wisconsin  54449
Loma Linda University Medical CenterLoma Linda, California  92354
Baptist Hospital of MiamiMiami, Florida  33176-2197
Newark Beth Israel Medical CenterNewark, New Jersey  07112
New York Medical CollegeValhalla, New York  10595
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
Cedars-Sinai Medical CenterLos Angeles, California  90048
University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
Madigan Army Medical CenterTacoma, Washington  98431-5048
Eastern Maine Medical CenterBangor, Maine  04401
William Beaumont HospitalRoyal Oak, Michigan  48073
University of Nebraska Medical CenterOmaha, Nebraska  68198-3330
Hackensack University Medical CenterHackensack, New Jersey  07601
Children's Hospital Los AngelesLos Angeles, California  90027-0700
Children's National Medical CenterWashington, District of Columbia  20010-2970
Miami Children's HospitalMiami, Florida  33155-4069
All Children's HospitalSt. Petersburg, Florida  33701
Advocate Hope Children's HospitalOak Lawn, Illinois  60453
Saint Jude Midwest AffiliatePeoria, Illinois  61637
Maine Children's Cancer ProgramScarborough, Maine  04074-9308
Carolinas Medical CenterCharlotte, North Carolina  28232-2861
University of Oklahoma Health Sciences CenterOklahoma City, Oklahoma  73104
Legacy Emanuel Hospital and Health CenterPortland, Oregon  97227
St. Jude Children's Research HospitalMemphis, Tennessee  38105-2794
Driscoll Children's HospitalCorpus Christi, Texas  78466
Scott and White Memorial HospitalTemple, Texas  76508
Inova Fairfax HospitalFalls Church, Virginia  22042-3300
Southern California Permanente Medical GroupDowney, California  90242
Children's Hospital Central CaliforniaMadera, California  93638-8762
Santa Barbara Cottage HospitalSanta Barbara, California  93102
Kosair Children's HospitalLouisville, Kentucky  40202-3830
Brooklyn Hospital CenterBrooklyn, New York  11201
Children's Hospital Medical Center of AkronAkron, Ohio  44308
Covenant Children's HospitalLubbock, Texas  79410
University of Wisconsin Hospital and ClinicsMadison, Wisconsin  53792-0001
Overlook HospitalSummit, New Jersey  07902-0220
Winthrop University HospitalMineola, New York  11501
Mount Sinai Medical CenterNew York, New York  10029
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Methodist Children's Hospital of South TexasSan Antonio, Texas  78229-3993
Primary Children's Medical CenterSalt Lake City, Utah  84113-1100
Montefiore Medical CenterBronx, New York  10467-2490
Saint Peter's University HospitalNew Brunswick, New Jersey  08901-1780
Rady Children's Hospital - San DiegoSan Diego, California  92123-4282
Children's Hospitals and Clinics of Minnesota - MinneapolisMinneapolis, Minnesota  55404
University of New Mexico Cancer CenterAlbuquerque, New Mexico  87131-5636
Nationwide Children's HospitalColumbus, Ohio  43205-2696
Children's Hospital of Pittsburgh of UPMCPittsburgh, Pennsylvania  15213
Dell Children's Medical Center of Central TexasAustin, Texas  78723
Children's Hospital and Research Center at OaklandOakland, California  94609-1809
Mary Bridge Children's Hospital and Health CenterTacoma, Washington  98415-0299
City of Hope Medical CenterDuarte, California  91010
Lehigh Valley Hospital - MuhlenbergBethlehem, Pennsylvania  18017
Presbyterian HospitalCharlotte, North Carolina  28233-3549
Lee Memorial Health SystemFort Myers, Florida  33902
University of VirginiaCharlottesville, Virginia  22908
University of Alabama at BirminghamBirmingham, Alabama  35294-3300
Children's Hospital of AlabamaBirmingham, Alabama  35233
Connecticut Children's Medical CenterHartford, Connecticut  06106
University of North CarolinaChapel Hill, North Carolina  27599
Duke University Medical CenterDurham, North Carolina  27710
University of FloridaGainesville, Florida  32610-0277
University of RochesterRochester, New York  14642
Nemours Children's Clinic - PensacolaPensacola, Florida  32504
Helen DeVos Children's Hospital at Spectrum HealthGrand Rapids, Michigan  49503
Yale UniversityNew Haven, Connecticut  06520
Wayne State UniversityDetroit, Michigan  48202
Mercy Children's HospitalToledo, Ohio  43608
Legacy Emanuel Children's HospitalPortland, Oregon  97227
BI-LO Charities Children's Cancer CenterGreenville, South Carolina  29605
University of Arizona Health Sciences CenterTucson, Arizona  85724
University of Massachusetts Medical SchoolWorcester, Massachusetts  01605
Dartmouth Hitchcock Medical CenterLebanon, New Hampshire  03756
University Of VermontBurlington,, Vermont  05403
Albany Medical CenterAlbany, New York  12208
University of Texas Southwestern Medical CenterDallas, Texas  
University of KentuckyLexington, Kentucky  40536-0098
UC Davis Comprehensive Cancer CenterSacramento, California  95817
Oregon Health and Science UniversityPortland, Oregon  97201
Tulane University Health Sciences CenterNew Orleans, Louisiana  70112
Virginia Commonwealth UniversityRichmond, Virginia  
David Geffen School of Medicine at UCLALos Angeles, California  90095
Florida HospitalOrlando, Florida  32803
Memorial Health University Medical CenterSavannah, Georgia  31404
University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470
M D Anderson Cancer CenterHouston, Texas  77030
Seattle Children's HospitalSeattle, Washington  98105
Wake Forest University Health SciencesWinston-Salem, North Carolina  27157
Childrens Memorial HospitalChicago, Illinois  60614
Kaiser Permanente-OaklandOakland, California  94611
Sutter General HospitalSacramento, California  95816
Lombardi Comprehensive Cancer Center at Georgetown UniversityWashington, District of Columbia  20057
M D Anderson Cancer Center- OrlandoOrlando, Florida  32806
University of HawaiiHonolulu, Hawaii  96813
Saint Luke's Mountain States Tumor InstituteBoise, Idaho  83712
Saint Vincent Hospital and Health ServicesIndianapolis, Indiana  46260
Saint John Hospital and Medical CenterDetroit, Michigan  48236
Michigan State University - Breslin Cancer CenterEast Lansing, Michigan  48824-1313
Kalamazoo Center for Medical StudiesKalamazoo, Michigan  49008
Saint John's Mercy Medical CenterSaint Louis, Missouri  63141
Nevada Cancer Research Foundation CCOPLas Vegas, Nevada  89106
New York University Langone Medical CenterNew York, New York  10016
Columbia University Medical CenterNew York, New York  10032
State University of New York Upstate Medical UniversitySyracuse, New York  13210
Mission Hospitals IncAsheville, North Carolina  28801
Natalie W Bryant Cancer CenterTulsa, Oklahoma  74136
Saint Vincent HospitalGreen Bay, Wisconsin  54301
University of Maryland Greenebaum Cancer CenterBaltimore, Maryland  21201
University of IllinoisChicago, Illinois  60612
Stony Brook University Medical CenterStony Brook, New York  11794
Cook Children's Medical CenterFort Worth, Texas  76104
Memorial Healthcare System - Joe DiMaggio Children's HospitalHollywood, Florida  33021
West Virginia University CharlestonCharleston, West Virginia  25304
The Children's Medical Center of DaytonDayton, Ohio  45404
Advocate Lutheran General HospitalPark Ridge, Illinois  60068
University of Miami Miller School of Medicine-Sylvester Cancer CenterMiami, Florida  33136
University of Minnesota Medical Center-FairviewMinneapolis, Minnesota  55455
Children's Oncology GroupArcadia, California  91006-3776
C S Mott Children's HospitalAnn Arbor, Michigan  48109
Southern Illinois UniversitySpringfield, Illinois  62702
University Of Missouri-ColumbiaColumbia, Missouri  65212
Walter Reed National Military Medical CenterBethesda, Maryland  20889
Riley Hospital for ChildrenIndianapolis, Indiana  46202
UMDNJ - Robert Wood Johnson University HospitalNew Brunswick, New Jersey  08903
Phoenix Childrens HospitalPhoenix, Arizona  85016
Miller Children's HospitalLong Beach, California  90806
Childrens Hospital of Orange CountyOrange, California  92868-3874
Alfred I duPont Hospital for ChildrenWilmington, Delaware  19803
Nemours Children's Clinic - JacksonvilleJacksonville, Florida  32207-8426
Nemours Childrens Clinic - OrlandoOrlando, Florida  32806
Saint Joseph Children's Hospital of TampaTampa, Florida  33607
Children's Healthcare of Atlanta - EglestonAtlanta, Georgia  30322
The Childrens Mercy HospitalKansas City, Missouri  64108
Rainbow Babies and Childrens HospitalCleveland, Ohio  44106
Penn State Hershey Children's HospitalHershey, Pennsylvania  17033
Palmetto Health RichlandColumbia, South Carolina  29203
East Tennessee Childrens HospitalKnoxville, Tennessee  37916
Saint Mary's HospitalWest Palm Beach, Florida  33407
Children's Hospital and Medical Center of OmahaOmaha, Nebraska  68114
Saint Joseph's Regional Medical CenterPaterson, New Jersey  07503
Texas Tech University Health Science Center-AmarilloAmarillo, Texas  79106
Childrens Hospital-King's DaughtersNorfolk, Virginia  23507
Sanford Medical Center-FargoFargo, North Dakota  58122
Children's Hospital ColoradoAurora, Colorado  80045
Lucile Packard Children's Hospital Stanford UniversityPalo Alto, California  94304
University of California San Francisco Medical Center-ParnassusSan Francisco, California  94143
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical CenterDenver, Colorado  80218
Raymond Blank Children's HospitalDes Moines, Iowa  50309
Children's Hospital-Main CampusNew Orleans, Louisiana  70118
The Toledo Hospital/Toledo Children's HospitalToledo, Ohio  43606
Greenville Cancer Treatment CenterGreenville, South Carolina  29605
Sanford USD Medical Center - Sioux FallsSioux Falls, South Dakota  57117-5134
T C Thompson Children's HospitalChattanooga, Tennessee  37403
Providence Sacred Heart Medical Center and Children's HospitalSpokane, Washington  99204
Broward Health Medical CenterFort Lauderdale, Florida  33316
The Steven and Alexandra Cohen Children's Medical Center of New YorkNew Hyde Park, New York  11040
Mattel Children's Hospital UCLALos Angeles, California  90095