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Combination Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Rhabdomyosarcoma

Sponsor
Children's Oncology Group (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT00354835
Collaborator
National Cancer Institute (NCI) (NIH)
481
Enrollment
212
Locations
2
Arms
2.3
Patients Per Site

Study Details

Study Description

Brief Summary

This randomized phase III trial is studying two different combination chemotherapy regimens to compare how well they work when given together with radiation therapy in treating patients with newly diagnosed rhabdomyosarcoma. Drugs used in chemotherapy, such as vincristine sulfate, dactinomycin, cyclophosphamide, and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with radiation therapy may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective when given together with radiation therapy in treating patients with rhabdomyosarcoma.

Condition or Disease Intervention/Treatment Phase
  • Drug: Irinotecan Hydrochloride
  • Biological: Dactinomycin
  • Drug: Cyclophosphamide
  • Drug: Vincristine Sulfate
  • Radiation: Radiation Therapy
  • Other: Laboratory Biomarker Analysis
  • Other: Questionnaire Administration
 Phase 3

Detailed Description

PRIMARY OBJECTIVES:
  1. To compare the early response rates, failure-free survival (FFS), and survival of patients with intermediate-risk rhabdomyosarcoma (RMS) treated with surgery, radiotherapy, and vincristine (vincristine sulfate), dactinomycin and cyclophosphamide (VAC) or VAC alternating with vincristine, irinotecan (irinotecan hydrochloride) (VI).
SECONDARY OBJECTIVES:

  1. To 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 Intergroup Rhabdomyosarcoma Study (IRS)-IV for historic comparison.

  2. To compare the acute and late effects of VAC to VAC alternating with VI, including the toxicity associated with concurrent VI and radiotherapy.

  3. To compare the acute and late effects of VAC as delivered on this study to D9803 VAC.

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

  5. For VI treated patients, to correlate patient UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) genotype with VI toxicity. VI. To correlate cytochrome P450, family 2, subfamily B, polypeptide 6 (CYP2B6), cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9), and glutathione S-transferase alpha 1 (GSTA1) genotypes with VAC toxicity.

  6. To prospectively evaluate and validate gene expression values with the intent to define the best diagnostic predictors and more powerful prognostic classifiers.

  7. To assess the frequency of bladder dysfunction in patients with bladder, prostate, and pelvic sites of RMS 3-6 years after study enrollment.

OUTLINE: 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 sulfate 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 sulfate 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 up every 2-4 months for 4 years and then annually for 5-10 years.

Study Design

Study Type:
Interventional
Actual Enrollment :
481 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Randomized Study of Vincristine, Dactinomycin and Cyclophosphamide (VAC) Versus VAC Alternating With Vincristine and Irinotecan (VI) for Patients With Intermediate-Risk Rhabdomyosarcoma (RMS)
Study Start Date :
Dec 1, 2006
Actual Primary Completion Date :
Dec 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: 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. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.

Biological: Dactinomycin
Given IV
Other Names:
  • Lyovac Cosmegen

    • Drug: Cyclophosphamide
    Given IV

    Drug: Vincristine Sulfate
    Given IV
    Other Names:
  • Kyocristine
  • Oncovin
  • VCR
  • Vincasar

    • Radiation: Radiation Therapy
    Undergo radiotherapy
    Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • Irradiation
  • RT

    • Other: Laboratory Biomarker Analysis
    Correlative studies

    Other: Questionnaire Administration
    Ancillary studies
    Experimental: VAC Alternating with 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 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.

    Drug: Irinotecan Hydrochloride
    Given IV

    Biological: Dactinomycin
    Given IV
    Other Names:
  • Lyovac Cosmegen

    • Drug: Cyclophosphamide
    Given IV

    Drug: Vincristine Sulfate
    Given IV
    Other Names:
  • Kyocristine
  • Oncovin
  • VCR
  • Vincasar

    • Radiation: Radiation Therapy
    Undergo radiotherapy
    Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • Irradiation
  • RT

    • Other: Laboratory Biomarker Analysis
    Correlative studies

    Other: Questionnaire Administration
    Ancillary studies

    Outcome Measures

    Primary Outcome Measures

    1. Event Free Survival (EFS) [4 years]

      Probability of no relapse, secondary malignancy, or death after 4 year in the study

    2. Response Rate (RR) [Reporting Period 1 (Weeks 1 - 15)]

      Proportion of patients with complete or partial response. Complete Response (CR): Complete disappearance of the tumor confirmed at > 4 weeks; Partial Response (PR): At least 64% decrease in volume compared to the baseline; Overall Response (OR) = CR + PR.

    3. Overall Survival (OS) [4 years]

      Probability of being alive after 4 years in the study.

    Secondary Outcome Measures

    1. Event Free Survival (EFS) Probability VAC and Early (Week 4) Radiotherapy Compared to Delayed (Week 10) Radiotherapy, Using IRSIV for Historic Comparison [4 years]

      Compare 4-year EFS using eligible participants only to the historical rate of 0.65 with IRSI-V. The 4-year EFS is probability of no relapse, secondary malignancy, or death after 4 years in the study. The Delayed (Week 10) Radiotherapy is from IRSI-V, and the number of participants of IRSI-V is unknown, but we have the rate of 0.65.

    2. Local Failure [2 years]

      Compare 2-year local failure rate to the historical rate of 0.13 with IRSI-V. The Delayed (Week 10) Radiotherapy is from IRSI-V, and the number of participants of IRSI-V is unknown, but we have the rate of 0.13.

    3. Overall Survival (OS) Probability VAC and Early (Week 4) Radiotherapy Compared to Delayed (Week 10) Radiotherapy, Using IRSIV for Historic Comparison [4 years]

      Compare 4-year OS using eligible participants only to the historical rate of 0.70 with IRSI-V. The 4-year OS is probability of being alive after 4 years in the study. The Delayed (Week 10) Radiotherapy is from IRSI-V, and the number of participants of IRSI-V is unknown, but we have the rate of 0.70.

    4. Incidence of Toxicity [Up to 15 weeks]

      Grade 3 or 4 nausea, diarrhea, dehydration, radiation dermatitis, mucositis due to radiation. Severe and undesirable adverse event is considered as grade 3; Life-threatening or disabling adverse event is grade 4. Grade 4 is worse than grade 3.

    5. Acute and Late Effects of VAC as Delivered on This Study to D9803 VAC [Up to 43 weeks]

      The toxicity rates will be estimated for each phase and course of treatment, and will be compared to the fixed rates under D9803 using one-sided lower confidence intervals for a single proportion without adjustment for multiple comparisons.

    6. Compare Event Free Survival (EFS) With Respect to the Level of % Change in FDG PET Maximum Standard Uptake Value (SUVmax) at Week 4 [4 years]

      4-year EFS (probability of no relapse, secondary malignancy, or death after 4 years in the study).

    7. Compare Event Free Survival (EFS) With Respect to the Level of % Change in FDG PET Maximum Standard Uptake Value (SUVmax) at Week 15 [4 years]

      4-year EFS (probability of no relapse, secondary malignancy, or death after 4 years in the study)

    8. Incidence of Toxicity Related to VI Treatment in Patients With UGT1A1 Genotype [Weeks 4-9 (the first exposure to VI)]

      Severe and undesirable adverse event is considered as grade 3; Life-threatening or disabling adverse event is grade 4. Grade 4 is worse than grade 3.

    9. Toxicity With CYP2B6 Genotypes [During the study]

      Incidence of toxicity related to VAC treatment in patients with CYP2B6 genotypes.

    10. Toxicity With GSTA1 and CYP2C9 Genotypes [During the study]

      Incidence of toxicity related to VAC treatment in patients with GSTA1 and CYP2C9 genotypes.

    11. Event Free Survival (EFS) by PAX Status [4 years]

    12. Incidence of Bladder Dysfunction [3-6 years after enrollment]

      Number of patients with a summary score greater than 8.5

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A to 49 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Patients with newly diagnosed embryonal RMS, botryoid or spindle cell variants of embryonal RMS, ectomesenchymoma, or alveolar RMS are eligible for this study

    • Enrollment on COG-D9902 to confirm local histologic diagnosis with central pathology review is required for all patients

    • Patients may be enrolled on ARST0531 and start protocol treatment prior to receipt of central pathology review results

    • Patient must have Intermediate-risk RMS defined as:

    • Embryonal, botryoid, or spindle cell RMS, or ectomesenchymoma: stage 2 or 3 and group III OR

    • Alveolar RMS: stage 1-3 and group I-III

    • Staging ipsilateral retroperitoneal lymph node dissection (SIRLND) is required for all patients >= 10 years of age with paratesticular tumors and for patients < 10 years with clinically or radiographically involved lymph nodes (except when extensive lymph node involvement, defined as two or more lymph nodes > 2 cm in dimension, is identified by imaging studies)

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

    • Clinically or radiographically enlarged nodes should be sampled for histologic evaluation

    • Detection of metastasis by optional FDG PET (not required for study enrollment); FDG PET may detect abnormalities suggestive of metastasis not identified by bone scan, computed tomography (CT), or bone marrow aspiration/biopsy; the prognostic significance of FDG PET-detected abnormalities is not clear; FDG PET-detected abnormalities MUST be confirmed to be metastases by an additional imaging modality (such as magnetic resonance imaging [MRI] or CT) OR pathologic confirmation; unless FDG PET abnormalities are confirmed by another imaging modality or biopsy, FDG PET abnormalities will NOT be considered evidence of metastasis

    • Patients must have a performance status of 0, 1, or 2; the Lansky performance score should be used for patients < 16 years and the Karnofsky performance score for patients >= 16 years

    • Patients who have received prior chemotherapy (excluding steroids) or radiation therapy, except for patients transferring from ARST0331 (low-risk study), are not eligible

    • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

    • 1 month to < 6 months: 0.4 mg/dL

    • 6 months to < 1 year: 0.5 mg/dL

    • 1 to < 2 years: 0.6 mg/dL

    • 2 to < 6 years: 0.8 mgt/dL

    • 6 to < 10 years: 1 mg/dL

    • 10 to < 13 years: 1.2 mg/dL

    • 13 to < 16 years: 1.5 mg/dL (males) or 1.4 mg/dL (females)

    • = 16 years: 1.7 mg/dL (males) or 1.4 mg/dL (females)

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

    • Total bilirubin =< 1.5 x upper limit of normal for age

    • Peripheral absolute neutrophil count (ANC) >= 750/uL

    • Platelet count >= 75,000/uL (transfusion independent)

    • No evidence of uncontrolled infection

    • Patients must be able to undergo radiation therapy, if necessary, as specified in the protocol

    • Female patients of childbearing potential must have a negative pregnancy test

    • Female patients who are breast feeding must agree to stop breast feeding

    • Sexually active patients of childbearing potential must be willing to use effective contraception during therapy and for at least 1 month after treatment is completed

    • All patients and/or their parents or legal guardians must sign a written informed consent

    • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Children's Hospital of Alabama Birmingham Alabama United States 35233
    2 University of Alabama at Birmingham Birmingham Alabama United States 35233
    3 Phoenix Childrens Hospital Phoenix Arizona United States 85016
    4 University of Arizona Health Sciences Center Tucson Arizona United States 85724
    5 Arkansas Children's Hospital Little Rock Arkansas United States 72202-3591
    6 University of Arkansas for Medical Sciences Little Rock Arkansas United States 72205
    7 Southern California Permanente Medical Group Downey California United States 90242
    8 City of Hope Medical Center Duarte California United States 91010
    9 Loma Linda University Medical Center Loma Linda California United States 92354
    10 Miller Children's Hospital Long Beach California United States 90806
    11 Children's Hospital Los Angeles Los Angeles California United States 90027
    12 Cedars-Sinai Medical Center Los Angeles California United States 90048
    13 David Geffen School of Medicine at UCLA Los Angeles California United States 90095
    14 Mattel Children's Hospital UCLA Los Angeles California United States 90095
    15 Children's Hospital Central California Madera California United States 93636-8762
    16 Children's Hospital and Research Center at Oakland Oakland California United States 94609-1809
    17 Kaiser Permanente-Oakland Oakland California United States 94611
    18 Childrens Hospital of Orange County Orange California United States 92868
    19 Lucile Packard Children's Hospital Stanford University Palo Alto California United States 94304
    20 Sutter General Hospital Sacramento California United States 95816
    21 University of California Davis Comprehensive Cancer Center Sacramento California United States 95817
    22 Rady Children's Hospital - San Diego San Diego California United States 92123
    23 University of California San Francisco Medical Center-Parnassus San Francisco California United States 94143
    24 Santa Barbara Cottage Hospital Santa Barbara California United States 93102
    25 Children's Hospital Colorado Aurora Colorado United States 80045
    26 Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center Denver Colorado United States 80218
    27 Connecticut Children's Medical Center Hartford Connecticut United States 06106
    28 Yale University New Haven Connecticut United States 06520
    29 Alfred I duPont Hospital for Children Wilmington Delaware United States 19803
    30 Children's National Medical Center Washington District of Columbia United States 20010
    31 Lombardi Comprehensive Cancer Center at Georgetown University Washington District of Columbia United States 20057
    32 Broward Health Medical Center Fort Lauderdale Florida United States 33316
    33 Lee Memorial Health System Fort Myers Florida United States 33901
    34 Golisano Children's Hospital of Southwest Florida Fort Myers Florida United States 33908
    35 University of Florida Gainesville Florida United States 32610
    36 Memorial Healthcare System - Joe DiMaggio Children's Hospital Hollywood Florida United States 33021
    37 Nemours Children's Clinic-Jacksonville South Jacksonville Florida United States 32207
    38 University of Miami Miller School of Medicine-Sylvester Cancer Center Miami Florida United States 33136
    39 Miami Children's Hospital Miami Florida United States 33155
    40 Baptist Hospital of Miami Miami Florida United States 33176
    41 Florida Hospital Orlando Orlando Florida United States 32803
    42 Nemours Children's Clinic - Orlando Orlando Florida United States 32806
    43 UF Cancer Center at Orlando Health Orlando Florida United States 32806
    44 Nemours Children's Hospital Orlando Florida United States 32827
    45 Nemours Children's Clinic - Pensacola Pensacola Florida United States 32504
    46 All Children's Hospital Saint Petersburg Florida United States 33701
    47 Saint Joseph Children's Hospital of Tampa Tampa Florida United States 33607
    48 Saint Mary's Hospital West Palm Beach Florida United States 33407
    49 Children's Healthcare of Atlanta - Egleston Atlanta Georgia United States 30322
    50 Memorial University Medical Center Savannah Georgia United States 31404
    51 University of Hawaii Cancer Center Honolulu Hawaii United States 96813
    52 Saint Luke's Mountain States Tumor Institute Boise Idaho United States 83712
    53 Lurie Children's Hospital-Chicago Chicago Illinois United States 60611
    54 University of Illinois Chicago Illinois United States 60612
    55 University of Chicago Comprehensive Cancer Center Chicago Illinois United States 60637
    56 Loyola University Medical Center Maywood Illinois United States 60153
    57 Advocate Children's Hospital-Oak Lawn Oak Lawn Illinois United States 60453
    58 Advocate Lutheran General Hospital. Park Ridge Illinois United States 60068
    59 Saint Jude Midwest Affiliate Peoria Illinois United States 61602
    60 Southern Illinois University Springfield Illinois United States 62702
    61 Indiana University/Melvin and Bren Simon Cancer Center Indianapolis Indiana United States 46202
    62 Riley Hospital for Children Indianapolis Indiana United States 46202
    63 Saint Vincent Hospital and Health Services Indianapolis Indiana United States 46260
    64 Blank Children's Hospital Des Moines Iowa United States 50309
    65 University of Iowa Hospitals and Clinics Iowa City Iowa United States 52242
    66 University of Kentucky/Markey Cancer Center Lexington Kentucky United States 40536
    67 Kosair Children's Hospital Louisville Kentucky United States 40202
    68 Tulane University Health Sciences Center New Orleans Louisiana United States 70112
    69 Children's Hospital New Orleans New Orleans Louisiana United States 70118
    70 Eastern Maine Medical Center Bangor Maine United States 04401
    71 Maine Children's Cancer Program Scarborough Maine United States 04074
    72 University of Maryland/Greenebaum Cancer Center Baltimore Maryland United States 21201
    73 Sinai Hospital of Baltimore Baltimore Maryland United States 21215
    74 Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center Baltimore Maryland United States 21287
    75 Walter Reed National Military Medical Center Bethesda Maryland United States 20889-5600
    76 Massachusetts General Hospital Cancer Center Boston Massachusetts United States 02114
    77 Dana-Farber Cancer Institute Boston Massachusetts United States 02115
    78 Baystate Medical Center Springfield Massachusetts United States 01199
    79 University of Massachusetts Medical School Worcester Massachusetts United States 01655
    80 C S Mott Children's Hospital Ann Arbor Michigan United States 48109
    81 Wayne State University/Karmanos Cancer Institute Detroit Michigan United States 48201
    82 Saint John Hospital and Medical Center Detroit Michigan United States 48236
    83 Michigan State University Clinical Center East Lansing Michigan United States 48824-7016
    84 Hurley Medical Center Flint Michigan United States 48502
    85 Helen DeVos Children's Hospital at Spectrum Health Grand Rapids Michigan United States 49503
    86 Bronson Methodist Hospital Kalamazoo Michigan United States 49007
    87 Kalamazoo Center for Medical Studies Kalamazoo Michigan United States 49008
    88 Beaumont Children's Hospital-Royal Oak Royal Oak Michigan United States 48073
    89 William Beaumont Hospital-Royal Oak Royal Oak Michigan United States 48073
    90 Children's Hospitals and Clinics of Minnesota - Minneapolis Minneapolis Minnesota United States 55404
    91 University of Minnesota Medical Center-Fairview Minneapolis Minnesota United States 55455
    92 Mayo Clinic Rochester Minnesota United States 55905
    93 University of Mississippi Medical Center Jackson Mississippi United States 39216
    94 University of Missouri - Ellis Fischel Columbia Missouri United States 65212
    95 The Childrens Mercy Hospital Kansas City Missouri United States 64108
    96 Washington University School of Medicine Saint Louis Missouri United States 63110
    97 Saint John's Mercy Medical Center Saint Louis Missouri United States 63141
    98 Children's Hospital and Medical Center of Omaha Omaha Nebraska United States 68114
    99 University of Nebraska Medical Center Omaha Nebraska United States 68198
    100 Nevada Cancer Research Foundation CCOP Las Vegas Nevada United States 89106
    101 Dartmouth Hitchcock Medical Center Lebanon New Hampshire United States 03756
    102 Hackensack University Medical Center Hackensack New Jersey United States 07601
    103 Morristown Memorial Hospital Morristown New Jersey United States 07962
    104 Saint Peter's University Hospital New Brunswick New Jersey United States 08901
    105 UMDNJ - Robert Wood Johnson University Hospital New Brunswick New Jersey United States 08903
    106 Newark Beth Israel Medical Center Newark New Jersey United States 07112
    107 Saint Joseph's Regional Medical Center Paterson New Jersey United States 07503
    108 Overlook Hospital Summit New Jersey United States 07902
    109 University of New Mexico Cancer Center Albuquerque New Mexico United States 87106
    110 University of New Mexico Albuquerque New Mexico United States 87106
    111 Albany Medical Center Albany New York United States 12208
    112 Montefiore Medical Center - Moses Campus Bronx New York United States 10467-2490
    113 Brooklyn Hospital Center Brooklyn New York United States 11201
    114 Roswell Park Cancer Institute Buffalo New York United States 14263
    115 Winthrop University Hospital Mineola New York United States 11501
    116 The Steven and Alexandra Cohen Children's Medical Center of New York New Hyde Park New York United States 11040
    117 New York University Langone Medical Center New York New York United States 10016
    118 Mount Sinai Medical Center New York New York United States 10029
    119 Columbia University Medical Center New York New York United States 10032
    120 University of Rochester Rochester New York United States 14642
    121 Stony Brook University Medical Center Stony Brook New York United States 11794
    122 State University of New York Upstate Medical University Syracuse New York United States 13210
    123 New York Medical College Valhalla New York United States 10595
    124 Mission Hospital-Memorial Campus Asheville North Carolina United States 28801
    125 University of North Carolina Chapel Hill North Carolina United States 27599
    126 Carolinas Medical Center Charlotte North Carolina United States 28203
    127 Novant Health Presbyterian Medical Center Charlotte North Carolina United States 28204
    128 Duke University Medical Center Durham North Carolina United States 27710
    129 Wake Forest University Health Sciences Winston-Salem North Carolina United States 27157
    130 Sanford Medical Center-Fargo Fargo North Dakota United States 58122
    131 Children's Hospital Medical Center of Akron Akron Ohio United States 44308
    132 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229
    133 Rainbow Babies and Childrens Hospital Cleveland Ohio United States 44106
    134 Cleveland Clinic Foundation Cleveland Ohio United States 44195
    135 Nationwide Children's Hospital Columbus Ohio United States 43205
    136 Dayton Children's Hospital Dayton Ohio United States 45404
    137 The Toledo Hospital/Toledo Children's Hospital Toledo Ohio United States 43606
    138 Mercy Children's Hospital Toledo Ohio United States 43608
    139 University of Oklahoma Health Sciences Center Oklahoma City Oklahoma United States 73104
    140 Natalie Warren Bryant Cancer Center at Saint Francis Tulsa Oklahoma United States 74136
    141 Legacy Emanuel Children's Hospital Portland Oregon United States 97227
    142 Legacy Emanuel Hospital and Health Center Portland Oregon United States 97227
    143 Oregon Health and Science University Portland Oregon United States 97239
    144 Lehigh Valley Hospital - Muhlenberg Bethlehem Pennsylvania United States 18017
    145 Geisinger Medical Center Danville Pennsylvania United States 17822
    146 Penn State Hershey Children's Hospital Hershey Pennsylvania United States 17033
    147 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    148 Children's Hospital of Pittsburgh of UPMC Pittsburgh Pennsylvania United States 15224
    149 Rhode Island Hospital Providence Rhode Island United States 02903
    150 Medical University of South Carolina Charleston South Carolina United States 29425
    151 Palmetto Health Richland Columbia South Carolina United States 29203
    152 BI-LO Charities Children's Cancer Center Greenville South Carolina United States 29605
    153 Greenville Cancer Treatment Center Greenville South Carolina United States 29605
    154 Sanford USD Medical Center - Sioux Falls Sioux Falls South Dakota United States 57117-5134
    155 T C Thompson Children's Hospital Chattanooga Tennessee United States 37403
    156 East Tennessee Childrens Hospital Knoxville Tennessee United States 37916
    157 St. Jude Children's Research Hospital Memphis Tennessee United States 38105
    158 Vanderbilt-Ingram Cancer Center Nashville Tennessee United States 37232
    159 Texas Tech University Health Science Center-Amarillo Amarillo Texas United States 79106
    160 Dell Children's Medical Center of Central Texas Austin Texas United States 78723
    161 Driscoll Children's Hospital Corpus Christi Texas United States 78411
    162 Medical City Dallas Hospital Dallas Texas United States 75230
    163 University of Texas Southwestern Medical Center Dallas Texas United States 75390
    164 Cook Children's Medical Center Fort Worth Texas United States 76104
    165 Baylor College of Medicine Houston Texas United States 77030
    166 M D Anderson Cancer Center Houston Texas United States 77030
    167 Covenant Children's Hospital Lubbock Texas United States 79410
    168 Methodist Children's Hospital of South Texas San Antonio Texas United States 78229
    169 University of Texas Health Science Center at San Antonio San Antonio Texas United States 78229
    170 Scott and White Memorial Hospital Temple Texas United States 76508
    171 Primary Children's Hospital Salt Lake City Utah United States 84113
    172 University of Vermont College of Medicine Burlington Vermont United States 05405
    173 University of Virginia Charlottesville Virginia United States 22908
    174 Inova Fairfax Hospital Falls Church Virginia United States 22042
    175 Childrens Hospital-King's Daughters Norfolk Virginia United States 23507
    176 Virginia Commonwealth University/Massey Cancer Center Richmond Virginia United States 23298
    177 Seattle Children's Hospital Seattle Washington United States 98105
    178 Providence Sacred Heart Medical Center and Children's Hospital Spokane Washington United States 99204
    179 Mary Bridge Children's Hospital and Health Center Tacoma Washington United States 98405
    180 Madigan Army Medical Center Tacoma Washington United States 98431
    181 West Virginia University Charleston Charleston West Virginia United States 25304
    182 Saint Vincent Hospital Green Bay Wisconsin United States 54301
    183 University of Wisconsin Hospital and Clinics Madison Wisconsin United States 53792
    184 Marshfield Clinic Marshfield Wisconsin United States 54449
    185 Midwest Children's Cancer Center Milwaukee Wisconsin United States 53226
    186 Sydney Children's Hospital Randwick New South Wales Australia 2031
    187 The Children's Hospital at Westmead Westmead New South Wales Australia 2145
    188 Royal Brisbane and Women's Hospital Herston Queensland Australia 4029
    189 Royal Children's Hospital-Brisbane Herston Queensland Australia 4029
    190 Women's and Children's Hospital-Adelaide North Adelaide South Australia Australia 5006
    191 Royal Children's Hospital Parkville Victoria Australia 3052
    192 Princess Margaret Hospital for Children Perth Western Australia Australia 6008
    193 Alberta Children's Hospital Calgary Alberta Canada T3B 6A8
    194 University of Alberta Hospital Edmonton Alberta Canada T6G 2B7
    195 British Columbia Children's Hospital Vancouver British Columbia Canada V6H 3V4
    196 CancerCare Manitoba Winnipeg Manitoba Canada R3E 0V9
    197 Janeway Child Health Centre Saint John's Newfoundland and Labrador Canada A1B 3V6
    198 IWK Health Centre Halifax Nova Scotia Canada B3J 3G9
    199 McMaster Children's Hospital at Hamilton Health Sciences Hamilton Ontario Canada L8N 3Z5
    200 Chedoke-McMaster Hospitals Hamilton Ontario Canada L8S 4L8
    201 Cancer Centre of Southeastern Ontario at Kingston General Hospital Kingston Ontario Canada K7L 5P9
    202 Children's Hospital London Ontario Canada N6A 5W9
    203 Hospital for Sick Children Toronto Ontario Canada M5G 1X8
    204 The Montreal Children's Hospital of the MUHC Montreal Quebec Canada H3H 1P3
    205 Centre Hospitalier Universitaire Sainte-Justine Montreal Quebec Canada H3T 1C5
    206 Centre Hospitalier Universitaire de Quebec Ste-Foy Quebec Canada G1V 4G2
    207 Allan Blair Cancer Centre Regina Saskatchewan Canada S4T 7T1
    208 Saskatoon Cancer Centre Saskatoon Saskatchewan Canada S7N 4H4
    209 Starship Children's Hospital Grafton Auckland New Zealand 1145
    210 San Jorge Children's Hospital San Juan Puerto Rico 00912
    211 Swiss Pediatric Oncology Group - Bern Bern Switzerland 3010
    212 Swiss Pediatric Oncology Group - Geneva Geneva Switzerland 1205

    Sponsors and Collaborators

    • Children's Oncology Group
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Douglas Hawkins, MD, Children's Oncology Group

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Children's Oncology Group
    ClinicalTrials.gov Identifier:
    NCT00354835
    Other Study ID Numbers:
    • ARST0531
    • NCI-2009-00427
    • COG-ARST0531
    • CDR0000487560
    • ARST0531
    • ARST0531
    • U10CA098543
    • U10CA180886
    First Posted:
    Jul 20, 2006
    Last Update Posted:
    Dec 13, 2021
    Last Verified:
    Dec 1, 2021
    Additional relevant MeSH terms:
    Sarcoma
    Rhabdomyosarcoma
    Mesenchymoma
    Rhabdomyosarcoma, Alveolar
    Rhabdomyosarcoma, Embryonal
    Dactinomycin
    Cyclophosphamide
    Irinotecan
    Vincristine

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 481 excludes 33 ineligible cases (declared by the Study Chair) .
    Arm/Group Title Vincristine, Dactinomycin, Cyclophosphamide (VAC) VAC Alternating With Vincristine, Irinotecan (VI)
    Arm/Group Description 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. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. Dactinomycin: Given IV Cyclophosphamide: Given IV Vincristine Sulfate: Given IV Radiation Therapy: Undergo radiotherapy Laboratory Biomarker Analysis: Correlative studies Questionnaire Administration: Ancillary studies 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 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
    Period Title: Overall Study
    STARTED 239 242
    COMPLETED 187 181
    NOT COMPLETED 52 61

    Baseline Characteristics

    Arm/Group Title Vincristine, Dactinomycin, Cyclophosphamide (VAC) VAC Alternating With Vincristine, Irinotecan (VI) Total
    Arm/Group Description 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. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. 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 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. Total of all reporting groups
    Overall Participants 239 242 481
    Age (months) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [months]
    89.85
    (73.39)
    97.86
    (82.66)
    93.88
    (78.21)
    Sex: Female, Male (Count of Participants)
    Female
    109
    45.6%
    113
    46.7%
    222
    46.2%
    Male
    130
    54.4%
    129
    53.3%
    259
    53.8%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    39
    16.3%
    28
    11.6%
    67
    13.9%
    Not Hispanic or Latino
    191
    79.9%
    204
    84.3%
    395
    82.1%
    Unknown or Not Reported
    9
    3.8%
    10
    4.1%
    19
    4%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    2
    0.8%
    2
    0.8%
    4
    0.8%
    Asian
    7
    2.9%
    7
    2.9%
    14
    2.9%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    37
    15.5%
    29
    12%
    66
    13.7%
    White
    165
    69%
    181
    74.8%
    346
    71.9%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    28
    11.7%
    23
    9.5%
    51
    10.6%

    Outcome Measures

    1. Primary Outcome
    Title Event Free Survival (EFS)
    Description Probability of no relapse, secondary malignancy, or death after 4 year in the study
    Time Frame 4 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Vincristine, Dactinomycin, Cyclophosphamide (VAC) VAC Alternating With Vincristine, Irinotecan (VI)
    Arm/Group Description 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. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. Dactinomycin: Given IV Cyclophosphamide: Given IV Vincristine Sulfate: Given IV Radiation Therapy: Undergo radiotherapy Laboratory Biomarker Analysis: Correlative studies Questionnaire Administration: Ancillary studies 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 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
    Measure Participants 222 226
    Number (95% Confidence Interval) [Probability]
    0.6255
    0.5874
    2. Primary Outcome
    Title Response Rate (RR)
    Description Proportion of patients with complete or partial response. Complete Response (CR): Complete disappearance of the tumor confirmed at > 4 weeks; Partial Response (PR): At least 64% decrease in volume compared to the baseline; Overall Response (OR) = CR + PR.
    Time Frame Reporting Period 1 (Weeks 1 - 15)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Vincristine, Dactinomycin, Cyclophosphamide (VAC) VAC Alternating With Vincristine, Irinotecan (VI)
    Arm/Group Description 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. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. 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 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
    Measure Participants 222 226
    Number (95% Confidence Interval) [Proportion]
    0.6667
    0.6726
    3. Primary Outcome
    Title Overall Survival (OS)
    Description Probability of being alive after 4 years in the study.
    Time Frame 4 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Vincristine, Dactinomycin, Cyclophosphamide (VAC) VAC Alternating With Vincristine, Irinotecan (VI)
    Arm/Group Description 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. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. 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 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
    Measure Participants 222 226
    Number (95% Confidence Interval) [Probability]
    0.7293
    0.7223
    4. Secondary Outcome
    Title Event Free Survival (EFS) Probability VAC and Early (Week 4) Radiotherapy Compared to Delayed (Week 10) Radiotherapy, Using IRSIV for Historic Comparison
    Description Compare 4-year EFS using eligible participants only to the historical rate of 0.65 with IRSI-V. The 4-year EFS is probability of no relapse, secondary malignancy, or death after 4 years in the study. The Delayed (Week 10) Radiotherapy is from IRSI-V, and the number of participants of IRSI-V is unknown, but we have the rate of 0.65.
    Time Frame 4 years

    Outcome Measure Data

    Analysis Population Description
    17 ineligible participants were excluded.
    Arm/Group Title Vincristine, Dactinomycin, Cyclophosphamide (VAC)
    Arm/Group Description 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. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
    Measure Participants 222
    Number (95% Confidence Interval) [Probability]
    0.6255
    5. Secondary Outcome
    Title Local Failure
    Description Compare 2-year local failure rate to the historical rate of 0.13 with IRSI-V. The Delayed (Week 10) Radiotherapy is from IRSI-V, and the number of participants of IRSI-V is unknown, but we have the rate of 0.13.
    Time Frame 2 years

    Outcome Measure Data

    Analysis Population Description
    17 ineligible participants were excluded.
    Arm/Group Title Vincristine, Dactinomycin, Cyclophosphamide (VAC)
    Arm/Group Description 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. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
    Measure Participants 222
    Number (95% Confidence Interval) [Proportion of participants]
    0.1757
    0.1%
    6. Secondary Outcome
    Title Overall Survival (OS) Probability VAC and Early (Week 4) Radiotherapy Compared to Delayed (Week 10) Radiotherapy, Using IRSIV for Historic Comparison
    Description Compare 4-year OS using eligible participants only to the historical rate of 0.70 with IRSI-V. The 4-year OS is probability of being alive after 4 years in the study. The Delayed (Week 10) Radiotherapy is from IRSI-V, and the number of participants of IRSI-V is unknown, but we have the rate of 0.70.
    Time Frame 4 years

    Outcome Measure Data

    Analysis Population Description
    17 ineligible participants were excluded.
    Arm/Group Title Vincristine, Dactinomycin, Cyclophosphamide (VAC)
    Arm/Group Description 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. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
    Measure Participants 222
    Number (95% Confidence Interval) [Probability]
    0.7293
    7. Secondary Outcome
    Title Incidence of Toxicity
    Description Grade 3 or 4 nausea, diarrhea, dehydration, radiation dermatitis, mucositis due to radiation. Severe and undesirable adverse event is considered as grade 3; Life-threatening or disabling adverse event is grade 4. Grade 4 is worse than grade 3.
    Time Frame Up to 15 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Vincristine, Dactinomycin, Cyclophosphamide (VAC) VAC Alternating With Vincristine, Irinotecan (VI)
    Arm/Group Description 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. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. 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 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
    Measure Participants 222 226
    Number (95% Confidence Interval) [Probability]
    0.2072
    0.3673
    8. Secondary Outcome
    Title Acute and Late Effects of VAC as Delivered on This Study to D9803 VAC
    Description The toxicity rates will be estimated for each phase and course of treatment, and will be compared to the fixed rates under D9803 using one-sided lower confidence intervals for a single proportion without adjustment for multiple comparisons.
    Time Frame Up to 43 weeks

    Outcome Measure Data

    Analysis Population Description
    Number of patients with specific adverse events.
    Arm/Group Title VAC (Weeks 1-15) VAC (Weeks 31 - 43)
    Arm/Group Description Reporting period 1 (acute) Reporting period 3 (late)
    Measure Participants 222 193
    Anemia
    58
    24.3%
    54
    22.3%
    Febrile Neutropenia
    30
    12.6%
    17
    7%
    Nausea or Hepatopathy
    6
    2.5%
    1
    0.4%
    Platelet Count Decreased
    27
    11.3%
    63
    26%
    Vomiting
    9
    3.8%
    2
    0.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Vincristine, Dactinomycin, Cyclophosphamide (VAC)
    Comments Compare incidence of Anemia to historical rate of 0.40 from D9803, which is Randomized Study of VCR, Actinomycin-D, and CPM (VAC) vs. VAC alternating with VCR, Topotecan, and CPM (VTC) for Patients with Intermediate Risk RMS. Comparing the incidence of anemia with VAC on ARST0531 to the historical rate of 0.40 with VAC on D9803. The 95% one-sided confidence interval for the incidence of anemia will be calculated and evaluated to see if the interval contains the null rate of 0.40.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter The incidence of anemia
    Estimated Value 0.2613
    Confidence Interval (1-Sided) 95%
    to 0.31
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Vincristine, Dactinomycin, Cyclophosphamide (VAC)
    Comments Compare incidence of Nausea or Hepatopathy to historical rate of 0.05 from D9803, which is Randomized Study of VCR, Actinomycin-D, and CPM (VAC) vs. VAC alternating with VCR, Topotecan, and CPM (VTC) for Patients with Intermediate Risk RMS. The 95% one-sided confidence interval for the incidence of nausea or hepatopathy will be calculated and evaluated to see if the interval contains the null rate of 0.05.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter The incidence of nausea or hepatopathy
    Estimated Value 0.0270
    Confidence Interval (1-Sided) 95%
    to 0.0449
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Vincristine, Dactinomycin, Cyclophosphamide (VAC)
    Comments Compare incidence of Febrile Neutropenia to historical rate of 0.50 from D9803, which is Randomized Study of VCR, Actinomycin-D, and CPM (VAC) vs. VAC alternating with VCR, Topotecan, and CPM (VTC) for Patients with Intermediate Risk RMS. The 95% one-sided confidence interval for the incidence of febrile neutropenia will be calculated and evaluated to see if the interval contains the null rate of 0.50.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter The incidence of febrile neutropenia
    Estimated Value 0.1351
    Confidence Interval (1-Sided) 95%
    to 0.1729
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Vincristine, Dactinomycin, Cyclophosphamide (VAC)
    Comments Compare incidence of Platelet Count Decreased to historical rate of 0.70 from D9803, which is Randomized Study of VCR, Actinomycin-D, and CPM (VAC) vs. VAC alternating with VCR, Topotecan, and CPM (VTC) for Patients with Intermediate Risk RMS. The 95% one-sided confidence interval for the incidence of platelet count decreased will be calculated and evaluated to see if the interval contains the null rate of 0.70.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter The incidence of platelet count decrease
    Estimated Value 0.1216
    Confidence Interval (1-Sided) 95%
    to 0.1577
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Vincristine, Dactinomycin, Cyclophosphamide (VAC)
    Comments Compare incidence of Vomiting to historical rate of 0.15 from D9803, which is Randomized Study of VCR, Actinomycin-D, and CPM (VAC) vs. VAC alternating with VCR, Topotecan, and CPM (VTC) for Patients with Intermediate Risk RMS. The 95% one-sided confidence interval for the incidence of vomiting will be calculated and evaluated to see if the interval contains the null rate of 0.15.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter The incidence of vomiting
    Estimated Value 0.0405
    Confidence Interval (1-Sided) 95%
    to 0.0623
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection VAC Alternating With Vincristine, Irinotecan (VI)
    Comments Compare incidence of Anemia to historical rate of 0.40 from D9803, which is Randomized Study of VCR, Actinomycin-D, and CPM (VAC) vs. VAC alternating with VCR, Topotecan, and CPM (VTC) for Patients with Intermediate Risk RMS. 95% one-sided confidence interval for the incidence of anemia will be calculated and evaluated to see if the interval contains the null rate of 0.40.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter The incidence of anemia
    Estimated Value 0.2798
    Confidence Interval (1-Sided) 95%
    to 0.3329
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection VAC Alternating With Vincristine, Irinotecan (VI)
    Comments Compare incidence of Nausea or Hepatopathy to historical rate of 0.05 from D9803, which is Randomized Study of VCR, Actinomycin-D, and CPM (VAC) vs. VAC alternating with VCR, Topotecan, and CPM (VTC) for Patients with Intermediate Risk RMS. The 95% one-sided confidence interval for the incidence of nausea or hepatopathy will be calculated and evaluated to see if the interval contains the null rate of 0.05.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter The incidence of nausea or hepatopathy
    Estimated Value 0.0052
    Confidence Interval (1-Sided) 95%
    to 0.0137
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection VAC Alternating With Vincristine, Irinotecan (VI)
    Comments Compare incidence of Febrile Neutropenia to historical rate of 0.50 from D9803, which is Randomized Study of VCR, Actinomycin-D, and CPM (VAC) vs. VAC alternating with VCR, Topotecan, and CPM (VTC) for Patients with Intermediate Risk RMS. The 95% one-sided confidence interval for the incidence of febrile neutropenia will be calculated and evaluated to see if the interval contains the null rate of 0.50.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter The incidence of febrile neutropenia
    Estimated Value 0.0881
    Confidence Interval (1-Sided) 95%
    to 0.1216
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection VAC Alternating With Vincristine, Irinotecan (VI)
    Comments Compare incidence of Platelet Count Decreased to historical rate of 0.70 from D9803, which is Randomized Study of VCR, Actinomycin-D, and CPM (VAC) vs. VAC alternating with VCR, Topotecan, and CPM (VTC) for Patients with Intermediate Risk RMS. The 95% one-sided confidence interval for the incidence of platelet count decreased will be calculated and evaluated to see if the interval contains the null rate of 0.70.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter The incidence of platelet count decrease
    Estimated Value 0.3264
    Confidence Interval (1-Sided) 95%
    to 0.3819
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection VAC Alternating With Vincristine, Irinotecan (VI)
    Comments Compare incidence of Vomiting to historical rate of 0.15 from D9803, which is Randomized Study of VCR, Actinomycin-D, and CPM (VAC) vs. VAC alternating with VCR, Topotecan, and CPM (VTC) for Patients with Intermediate Risk RMS. The 95% one-sided confidence interval for the incidence of vomiting will be calculated and evaluated to see if the interval contains the null rate of 0.15.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter The incidence of vomiting
    Estimated Value 0.0104
    Confidence Interval (1-Sided) 95%
    to 0.0224
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title Compare Event Free Survival (EFS) With Respect to the Level of % Change in FDG PET Maximum Standard Uptake Value (SUVmax) at Week 4
    Description 4-year EFS (probability of no relapse, secondary malignancy, or death after 4 years in the study).
    Time Frame 4 years

    Outcome Measure Data

    Analysis Population Description
    452 participants were excluded due to ineligibility or absence of SUVmax evaluation at baseline and week 4.
    Arm/Group Title % Change in SUVmax From Baseline to Week 4 < 40% % Change in SUVmax From Baseline to Week 4 >= 40%
    Arm/Group Description
    Measure Participants 7 22
    Number (95% Confidence Interval) [Probability]
    0.2857
    0.6364
    10. Secondary Outcome
    Title Compare Event Free Survival (EFS) With Respect to the Level of % Change in FDG PET Maximum Standard Uptake Value (SUVmax) at Week 15
    Description 4-year EFS (probability of no relapse, secondary malignancy, or death after 4 years in the study)
    Time Frame 4 years

    Outcome Measure Data

    Analysis Population Description
    421 participants were excluded due to ineligibility or absence of SUVmax evaluation at baseline and week 15.
    Arm/Group Title % Change in SUVmax From Baseline to Week 15 < 40% % Change in SUVmax From Baseline to Week 15 >= 40%
    Arm/Group Description
    Measure Participants 9 51
    Number (95% Confidence Interval) [Probability]
    0.6667
    0.5686
    11. Secondary Outcome
    Title Incidence of Toxicity Related to VI Treatment in Patients With UGT1A1 Genotype
    Description Severe and undesirable adverse event is considered as grade 3; Life-threatening or disabling adverse event is grade 4. Grade 4 is worse than grade 3.
    Time Frame Weeks 4-9 (the first exposure to VI)

    Outcome Measure Data

    Analysis Population Description
    Ineligible patients are excluded. Only patients tested for the UGT1A1 genotypes are reported and included in this analysis.
    Arm/Group Title UGT1A1 Genotype 6/6 UGT1A1 Genotype 6/7 UGT1A1 Genotype 7/7
    Arm/Group Description
    Measure Participants 49 65 12
    Neutropenia, with or without Fever
    16
    22
    4
    Diarrhea
    5
    14
    5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Vincristine, Dactinomycin, Cyclophosphamide (VAC), VAC Alternating With Vincristine, Irinotecan (VI), UGT1A1 Genotype 7/7
    Comments The incidences of grade 3 or higher neutropenia, with or without fever between UGT1A1 Genotypes (6/6, 6/7, 7/7) were compared by the Fisher's exact test.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.99
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Vincristine, Dactinomycin, Cyclophosphamide (VAC), VAC Alternating With Vincristine, Irinotecan (VI), UGT1A1 Genotype 7/7
    Comments The incidences of grade 3 or higher diarrhea between UGT1A1 Genotypes (6/6, 6/7, 7/7) were compared by Fisher's exact test.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.036
    Comments
    Method Fisher Exact
    Comments
    12. Secondary Outcome
    Title Toxicity With CYP2B6 Genotypes
    Description Incidence of toxicity related to VAC treatment in patients with CYP2B6 genotypes.
    Time Frame During the study

    Outcome Measure Data

    Analysis Population Description
    The analysis was abandoned due to low incidence of toxicity. Data were not collected.
    Arm/Group Title Vincristine, Dactinomycin, Cyclophosphamide (VAC)
    Arm/Group Description 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. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
    Measure Participants 0
    13. Secondary Outcome
    Title Toxicity With GSTA1 and CYP2C9 Genotypes
    Description Incidence of toxicity related to VAC treatment in patients with GSTA1 and CYP2C9 genotypes.
    Time Frame During the study

    Outcome Measure Data

    Analysis Population Description
    The analysis was abandoned due to low incidence of toxicity. Data were not collected.
    Arm/Group Title Vincristine, Dactinomycin, Cyclophosphamide (VAC)
    Arm/Group Description
    Measure Participants 0
    14. Secondary Outcome
    Title Event Free Survival (EFS) by PAX Status
    Description
    Time Frame 4 years

    Outcome Measure Data

    Analysis Population Description
    Only eligible patients who were tested for their fusion status and PAX partners.
    Arm/Group Title PAX3 PAX7
    Arm/Group Description Fusion positive with PAX3 partner Fusion positive with PAX7 partner
    Measure Participants 88 21
    Number (95% Confidence Interval) [Probability]
    0.51
    0.66
    15. Secondary Outcome
    Title Incidence of Bladder Dysfunction
    Description Number of patients with a summary score greater than 8.5
    Time Frame 3-6 years after enrollment

    Outcome Measure Data

    Analysis Population Description
    470 participants were excluded due to ineligibility or absence of the dysfunctional voiding and incontinence symptoms questionnaire.
    Arm/Group Title Vincristine, Dactinomycin, Cyclophosphamide (VAC) VAC Alternating With Vincristine, Irinotecan (VI)
    Arm/Group Description 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. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. 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 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
    Measure Participants 7 4
    Number [Participant]
    2
    1

    Adverse Events

    Time Frame
    Adverse Event Reporting Description All eligible patients were considered in the evaluation of adverse events.
    Arm/Group Title Vincristine, Dactinomycin, Cyclophosphamide (VAC) VAC Alternating With VI
    Arm/Group Description 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. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. Dactinomycin: Given IV Cyclophosphamide: Given IV Vincristine Sulfate: Given IV Radiation Therapy: Undergo radiotherapy Laboratory Biomarker Analysis: Correlative studies Questionnaire Administration: Ancillary studies 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 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. Irinotecan Hydrochloride: Given IV Dactinomycin: Given IV Cyclophosphamide: Given IV Vincristine Sulfate: Given IV Radiation Therapy: Undergo radiotherapy Laboratory Biomarker Analysis: Correlative studies Questionnaire Administration: Ancillary studies
    All Cause Mortality
    Vincristine, Dactinomycin, Cyclophosphamide (VAC) VAC Alternating With VI
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Vincristine, Dactinomycin, Cyclophosphamide (VAC) VAC Alternating With VI
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/222 (1.8%) 11/226 (4.9%)
    Blood and lymphatic system disorders
    Anemia 1/222 (0.5%) 1 0/226 (0%) 0
    Gastrointestinal disorders
    Ascites 1/222 (0.5%) 1 0/226 (0%) 0
    Esophagitis 0/222 (0%) 0 1/226 (0.4%) 1
    Gastritis 0/222 (0%) 0 1/226 (0.4%) 1
    Gastrointestinal disorders - Other, specify 0/222 (0%) 0 1/226 (0.4%) 1
    Mucositis oral 0/222 (0%) 0 2/226 (0.9%) 2
    Oral pain 0/222 (0%) 0 1/226 (0.4%) 1
    General disorders
    Death NOS 0/222 (0%) 0 2/226 (0.9%) 2
    Hepatobiliary disorders
    Hepatic pain 1/222 (0.5%) 1 0/226 (0%) 0
    Hepatobiliary disorders - Other, specify 1/222 (0.5%) 1 0/226 (0%) 0
    Infections and infestations
    Sepsis 0/222 (0%) 0 1/226 (0.4%) 1
    Injury, poisoning and procedural complications
    Radiation recall reaction (dermatologic) 0/222 (0%) 0 1/226 (0.4%) 1
    Tracheal obstruction 0/222 (0%) 0 1/226 (0.4%) 1
    Investigations
    Alanine aminotransferase increased 1/222 (0.5%) 1 0/226 (0%) 0
    Aspartate aminotransferase increased 1/222 (0.5%) 1 0/226 (0%) 0
    Blood bilirubin increased 1/222 (0.5%) 1 0/226 (0%) 0
    Lymphocyte count decreased 0/222 (0%) 0 1/226 (0.4%) 1
    Platelet count decreased 1/222 (0.5%) 1 0/226 (0%) 0
    Metabolism and nutrition disorders
    Hypokalemia 0/222 (0%) 0 1/226 (0.4%) 1
    Hyponatremia 1/222 (0.5%) 1 0/226 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify 0/222 (0%) 0 1/226 (0.4%) 1
    Treatment related secondary malignancy 0/222 (0%) 0 1/226 (0.4%) 1
    Nervous system disorders
    Encephalopathy 0/222 (0%) 0 1/226 (0.4%) 1
    Intracranial hemorrhage 0/222 (0%) 0 1/226 (0.4%) 1
    Nervous system disorders - Other, specify 3/222 (1.4%) 3 0/226 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Pharyngeal mucositis 0/222 (0%) 0 1/226 (0.4%) 1
    Pharyngolaryngeal pain 0/222 (0%) 0 1/226 (0.4%) 1
    Pneumothorax 0/222 (0%) 0 1/226 (0.4%) 1
    Other (Not Including Serious) Adverse Events
    Vincristine, Dactinomycin, Cyclophosphamide (VAC) VAC Alternating With VI
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 209/222 (94.1%) 213/226 (94.2%)
    Blood and lymphatic system disorders
    Anemia 102/222 (45.9%) 183 57/226 (25.2%) 89
    Febrile neutropenia 62/222 (27.9%) 86 46/226 (20.4%) 57
    Cardiac disorders
    Cardiac arrest 0/222 (0%) 0 1/226 (0.4%) 1
    Ventricular fibrillation 0/222 (0%) 0 1/226 (0.4%) 1
    Ear and labyrinth disorders
    External ear inflammation 1/222 (0.5%) 1 0/226 (0%) 0
    Hearing impaired 1/222 (0.5%) 2 0/226 (0%) 0
    Eye disorders
    Extraocular muscle paresis 1/222 (0.5%) 1 0/226 (0%) 0
    Eye disorders - Other, specify 0/222 (0%) 0 1/226 (0.4%) 1
    Eyelid function disorder 1/222 (0.5%) 1 0/226 (0%) 0
    Optic nerve disorder 0/222 (0%) 0 2/226 (0.9%) 4
    Watering eyes 0/222 (0%) 0 1/226 (0.4%) 1
    Gastrointestinal disorders
    Abdominal distension 0/222 (0%) 0 2/226 (0.9%) 2
    Abdominal pain 9/222 (4.1%) 11 12/226 (5.3%) 14
    Anal mucositis 0/222 (0%) 0 1/226 (0.4%) 1
    Anal pain 1/222 (0.5%) 1 0/226 (0%) 0
    Colitis 1/222 (0.5%) 1 4/226 (1.8%) 4
    Constipation 4/222 (1.8%) 5 6/226 (2.7%) 6
    Diarrhea 14/222 (6.3%) 17 51/226 (22.6%) 63
    Dry mouth 0/222 (0%) 0 2/226 (0.9%) 3
    Dysphagia 3/222 (1.4%) 3 6/226 (2.7%) 6
    Enterocolitis 0/222 (0%) 0 1/226 (0.4%) 1
    Esophagitis 0/222 (0%) 0 3/226 (1.3%) 4
    Gastritis 2/222 (0.9%) 2 1/226 (0.4%) 1
    Gastrointestinal disorders - Other, specify 1/222 (0.5%) 1 2/226 (0.9%) 2
    Ileus 1/222 (0.5%) 1 6/226 (2.7%) 6
    Mucositis oral 25/222 (11.3%) 31 46/226 (20.4%) 48
    Nausea 8/222 (3.6%) 10 26/226 (11.5%) 41
    Oral pain 3/222 (1.4%) 4 7/226 (3.1%) 7
    Rectal pain 1/222 (0.5%) 1 0/226 (0%) 0
    Stomach pain 0/222 (0%) 0 2/226 (0.9%) 2
    Typhlitis 1/222 (0.5%) 1 3/226 (1.3%) 3
    Vomiting 16/222 (7.2%) 17 28/226 (12.4%) 37
    General disorders
    Edema trunk 1/222 (0.5%) 1 1/226 (0.4%) 1
    Facial pain 1/222 (0.5%) 1 3/226 (1.3%) 3
    Fatigue 0/222 (0%) 0 5/226 (2.2%) 5
    Fever 9/222 (4.1%) 10 11/226 (4.9%) 11
    General disorders and administration site conditions - Other, specify 1/222 (0.5%) 1 0/226 (0%) 0
    Pain 4/222 (1.8%) 9 9/226 (4%) 12
    Hepatobiliary disorders
    Cholecystitis 1/222 (0.5%) 1 0/226 (0%) 0
    Hepatic pain 1/222 (0.5%) 1 0/226 (0%) 0
    Portal hypertension 2/222 (0.9%) 2 0/226 (0%) 0
    Immune system disorders
    Anaphylaxis 4/222 (1.8%) 4 1/226 (0.4%) 1
    Infections and infestations
    Abdominal infection 0/222 (0%) 0 2/226 (0.9%) 2
    Anorectal infection 0/222 (0%) 0 1/226 (0.4%) 2
    Appendicitis 1/222 (0.5%) 1 0/226 (0%) 0
    Bladder infection 2/222 (0.9%) 2 3/226 (1.3%) 3
    Bronchial infection 0/222 (0%) 0 1/226 (0.4%) 1
    Catheter related infection 6/222 (2.7%) 8 13/226 (5.8%) 15
    Conjunctivitis infective 0/222 (0%) 0 1/226 (0.4%) 1
    Device related infection 2/222 (0.9%) 2 4/226 (1.8%) 5
    Enterocolitis infectious 5/222 (2.3%) 6 10/226 (4.4%) 10
    Esophageal infection 0/222 (0%) 0 1/226 (0.4%) 1
    Eye infection 0/222 (0%) 0 3/226 (1.3%) 3
    Gum infection 2/222 (0.9%) 2 0/226 (0%) 0
    Infections and infestations - Other, specify 40/222 (18%) 60 37/226 (16.4%) 56
    Lung infection 0/222 (0%) 0 4/226 (1.8%) 4
    Otitis media 0/222 (0%) 0 1/226 (0.4%) 1
    Paronychia 0/222 (0%) 0 1/226 (0.4%) 1
    Pleural infection 1/222 (0.5%) 1 0/226 (0%) 0
    Sepsis 1/222 (0.5%) 1 1/226 (0.4%) 1
    Sinusitis 3/222 (1.4%) 3 1/226 (0.4%) 1
    Skin infection 5/222 (2.3%) 5 7/226 (3.1%) 7
    Small intestine infection 1/222 (0.5%) 1 0/226 (0%) 0
    Soft tissue infection 1/222 (0.5%) 1 0/226 (0%) 0
    Upper respiratory infection 3/222 (1.4%) 4 4/226 (1.8%) 4
    Urethral infection 1/222 (0.5%) 1 0/226 (0%) 0
    Urinary tract infection 10/222 (4.5%) 11 8/226 (3.5%) 13
    Vaginal infection 0/222 (0%) 0 1/226 (0.4%) 1
    Vulval infection 1/222 (0.5%) 1 0/226 (0%) 0
    Wound infection 3/222 (1.4%) 3 1/226 (0.4%) 1
    Injury, poisoning and procedural complications
    Dermatitis radiation 6/222 (2.7%) 6 2/226 (0.9%) 2
    Fracture 1/222 (0.5%) 1 0/226 (0%) 0
    Radiation recall reaction (dermatologic) 1/222 (0.5%) 1 3/226 (1.3%) 3
    Seroma 0/222 (0%) 0 1/226 (0.4%) 1
    Vascular access complication 1/222 (0.5%) 1 2/226 (0.9%) 2
    Wound complication 0/222 (0%) 0 1/226 (0.4%) 1
    Wound dehiscence 0/222 (0%) 0 2/226 (0.9%) 2
    Investigations
    Activated partial thromboplastin time prolonged 1/222 (0.5%) 1 0/226 (0%) 0
    Alanine aminotransferase increased 19/222 (8.6%) 21 16/226 (7.1%) 22
    Alkaline phosphatase increased 1/222 (0.5%) 1 0/226 (0%) 0
    Aspartate aminotransferase increased 11/222 (5%) 13 7/226 (3.1%) 8
    Blood bilirubin increased 3/222 (1.4%) 3 1/226 (0.4%) 1
    GGT increased 2/222 (0.9%) 2 1/226 (0.4%) 1
    Hemoglobin increased 1/222 (0.5%) 1 0/226 (0%) 0
    Investigations - Other, specify 1/222 (0.5%) 1 0/226 (0%) 0
    Lipase increased 1/222 (0.5%) 1 2/226 (0.9%) 2
    Lymphocyte count decreased 48/222 (21.6%) 144 57/226 (25.2%) 148
    Neutrophil count decreased 179/222 (80.6%) 484 177/226 (78.3%) 436
    Platelet count decreased 94/222 (42.3%) 164 37/226 (16.4%) 52
    Serum amylase increased 1/222 (0.5%) 1 0/226 (0%) 0
    Weight gain 0/222 (0%) 0 2/226 (0.9%) 3
    Weight loss 13/222 (5.9%) 14 23/226 (10.2%) 32
    White blood cell decreased 100/222 (45%) 235 96/226 (42.5%) 219
    Metabolism and nutrition disorders
    Anorexia 24/222 (10.8%) 30 35/226 (15.5%) 42
    Dehydration 10/222 (4.5%) 10 23/226 (10.2%) 26
    Hyperglycemia 4/222 (1.8%) 4 11/226 (4.9%) 14
    Hyperkalemia 1/222 (0.5%) 1 3/226 (1.3%) 3
    Hypermagnesemia 1/222 (0.5%) 1 0/226 (0%) 0
    Hypernatremia 0/222 (0%) 0 2/226 (0.9%) 2
    Hypoalbuminemia 1/222 (0.5%) 1 1/226 (0.4%) 1
    Hypocalcemia 3/222 (1.4%) 3 4/226 (1.8%) 5
    Hypoglycemia 1/222 (0.5%) 1 1/226 (0.4%) 1
    Hypokalemia 24/222 (10.8%) 25 34/226 (15%) 40
    Hyponatremia 14/222 (6.3%) 16 15/226 (6.6%) 15
    Hypophosphatemia 7/222 (3.2%) 8 3/226 (1.3%) 4
    Metabolism and nutrition disorders - Other, specify 0/222 (0%) 0 1/226 (0.4%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/222 (0%) 0 1/226 (0.4%) 1
    Back pain 4/222 (1.8%) 4 0/226 (0%) 0
    Bone pain 1/222 (0.5%) 1 0/226 (0%) 0
    Muscle weakness lower limb 2/222 (0.9%) 4 1/226 (0.4%) 1
    Muscle weakness upper limb 0/222 (0%) 0 1/226 (0.4%) 1
    Musculoskeletal and connective tissue disorder - Other, specify 1/222 (0.5%) 1 0/226 (0%) 0
    Neck pain 0/222 (0%) 0 1/226 (0.4%) 1
    Pain in extremity 3/222 (1.4%) 3 2/226 (0.9%) 2
    Trismus 0/222 (0%) 0 1/226 (0.4%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumor pain 1/222 (0.5%) 1 1/226 (0.4%) 1
    Nervous system disorders
    Abducens nerve disorder 0/222 (0%) 0 1/226 (0.4%) 1
    Aphonia 1/222 (0.5%) 1 0/226 (0%) 0
    Ataxia 0/222 (0%) 0 3/226 (1.3%) 3
    Cognitive disturbance 1/222 (0.5%) 1 0/226 (0%) 0
    Depressed level of consciousness 0/222 (0%) 0 1/226 (0.4%) 1
    Dizziness 0/222 (0%) 0 2/226 (0.9%) 2
    Dysesthesia 0/222 (0%) 0 1/226 (0.4%) 1
    Encephalopathy 0/222 (0%) 0 2/226 (0.9%) 2
    Facial nerve disorder 0/222 (0%) 0 1/226 (0.4%) 1
    Headache 4/222 (1.8%) 6 3/226 (1.3%) 3
    Hypoglossal nerve disorder 0/222 (0%) 0 1/226 (0.4%) 1
    Nervous system disorders - Other, specify 1/222 (0.5%) 1 0/226 (0%) 0
    Neuralgia 1/222 (0.5%) 1 2/226 (0.9%) 2
    Nystagmus 0/222 (0%) 0 1/226 (0.4%) 1
    Oculomotor nerve disorder 0/222 (0%) 0 2/226 (0.9%) 4
    Peripheral motor neuropathy 29/222 (13.1%) 38 26/226 (11.5%) 44
    Peripheral sensory neuropathy 16/222 (7.2%) 21 13/226 (5.8%) 19
    Recurrent laryngeal nerve palsy 1/222 (0.5%) 1 0/226 (0%) 0
    Sinus pain 0/222 (0%) 0 1/226 (0.4%) 1
    Syncope 2/222 (0.9%) 2 2/226 (0.9%) 3
    Vagus nerve disorder 0/222 (0%) 0 1/226 (0.4%) 1
    Vasovagal reaction 0/222 (0%) 0 1/226 (0.4%) 1
    Psychiatric disorders
    Confusion 0/222 (0%) 0 1/226 (0.4%) 1
    Depression 0/222 (0%) 0 3/226 (1.3%) 3
    Insomnia 0/222 (0%) 0 1/226 (0.4%) 1
    Psychiatric disorders - Other, specify 0/222 (0%) 0 1/226 (0.4%) 1
    Renal and urinary disorders
    Bladder spasm 1/222 (0.5%) 1 2/226 (0.9%) 4
    Cystitis noninfective 1/222 (0.5%) 1 0/226 (0%) 0
    Hematuria 3/222 (1.4%) 4 1/226 (0.4%) 1
    Renal and urinary disorders - Other, specify 0/222 (0%) 0 2/226 (0.9%) 2
    Urinary retention 0/222 (0%) 0 1/226 (0.4%) 1
    Urinary tract obstruction 1/222 (0.5%) 1 0/226 (0%) 0
    Reproductive system and breast disorders
    Penile pain 1/222 (0.5%) 1 0/226 (0%) 0
    Vaginal pain 0/222 (0%) 0 1/226 (0.4%) 1
    Respiratory, thoracic and mediastinal disorders
    Atelectasis 2/222 (0.9%) 2 0/226 (0%) 0
    Cough 1/222 (0.5%) 1 1/226 (0.4%) 1
    Dyspnea 1/222 (0.5%) 1 1/226 (0.4%) 1
    Epistaxis 1/222 (0.5%) 1 1/226 (0.4%) 1
    Hypoxia 1/222 (0.5%) 1 6/226 (2.7%) 7
    Laryngeal edema 1/222 (0.5%) 1 2/226 (0.9%) 2
    Laryngeal mucositis 1/222 (0.5%) 1 0/226 (0%) 0
    Pharyngeal mucositis 3/222 (1.4%) 3 4/226 (1.8%) 4
    Pharyngolaryngeal pain 2/222 (0.9%) 2 1/226 (0.4%) 1
    Pleural effusion 1/222 (0.5%) 1 1/226 (0.4%) 1
    Respiratory failure 1/222 (0.5%) 1 0/226 (0%) 0
    Respiratory, thoracic and mediastinal disorders - Other, specify 0/222 (0%) 0 1/226 (0.4%) 1
    Stridor 0/222 (0%) 0 1/226 (0.4%) 1
    Tracheal mucositis 0/222 (0%) 0 1/226 (0.4%) 1
    Voice alteration 1/222 (0.5%) 1 0/226 (0%) 0
    Wheezing 1/222 (0.5%) 1 1/226 (0.4%) 1
    Skin and subcutaneous tissue disorders
    Rash maculo-papular 1/222 (0.5%) 1 2/226 (0.9%) 2
    Skin and subcutaneous tissue disorders - Other, specify 0/222 (0%) 0 1/226 (0.4%) 1
    Urticaria 1/222 (0.5%) 1 0/226 (0%) 0
    Vascular disorders
    Hypertension 0/222 (0%) 0 3/226 (1.3%) 5
    Hypotension 0/222 (0%) 0 1/226 (0.4%) 1
    Thromboembolic event 1/222 (0.5%) 1 3/226 (1.3%) 3
    Vascular disorders - Other, specify 1/222 (0.5%) 1 0/226 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Must obtain prior Sponsor approval.

    Results Point of Contact

    Name/Title Results Reporting Coordinator
    Organization Children's Oncology Group
    Phone 626-447-0064
    Email resultsreportingcoordinator@childrensoncologygroup.org
    Responsible Party:
    Children's Oncology Group
    ClinicalTrials.gov Identifier:
    NCT00354835
    Other Study ID Numbers:
    • ARST0531
    • NCI-2009-00427
    • COG-ARST0531
    • CDR0000487560
    • ARST0531
    • ARST0531
    • U10CA098543
    • U10CA180886
    First Posted:
    Jul 20, 2006
    Last Update Posted:
    Dec 13, 2021
    Last Verified:
    Dec 1, 2021