Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed, Non-metastatic Desmoplastic Medulloblastoma

Sponsor
Children's Oncology Group (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02017964
Collaborator
National Cancer Institute (NCI) (NIH)
26
173
1
107.3
0.2
0

Study Details

Study Description

Brief Summary

This phase II trial studies how well combination chemotherapy works in treating younger patients with newly diagnosed, non-metastatic desmoplastic medulloblastoma. Drugs used in chemotherapy, such as vincristine sulfate, cyclophosphamide, methotrexate, etoposide, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. Estimate of the progression free survival (PFS) distribution for patients 0-<4 years of age with M0 desmoplastic medulloblastoma (nodular desmoplastic or medulloblastoma with extensive nodularity) treated with the modified HIT SKK regimen (excluding the use of intraventricular methotrexate).
OTHER PRE-SPECIFIED OBJECTIVES:
  1. Evaluate the feasibility of a rapid central pathology screening review for treatment allocation according to histology and assess agreement between institutional and central pathology review diagnoses as well as among central pathology review diagnoses.

  2. Prospectively evaluate the molecular profile of nodular desmoplastic (ND)/medulloblastoma with extensive nodularity (MBEN) medulloblastoma in young children.

  3. Monitor and describe the neurocognitive and adaptive functioning of young children with ND/MBEN medulloblastoma treated on this protocol using the ALTE07C1 protocol.

OUTLINE:

INDUCTION THERAPY: Patients receive vincristine sulfate intravenously (IV) over 1 minute or infused via minibag on days 1, 15, and 29; cyclophosphamide IV over 1 hour on days 1-3; methotrexate IV over 24 hours on days 15 and 29; etoposide IV over 60-120 minutes on days 43-45; and carboplatin IV over 1 hour on days 43-45. Treatment repeats every 63 days for 3 courses in the absence of disease progression or unacceptable toxicity.

CONTINUATION THERAPY: Patients receive vincristine sulfate IV over 1 minute or infused via minibag on day 1, cyclophosphamide IV over 1 hour on days 1-3, etoposide IV over 60-120 minutes on days 21-23, and carboplatin IV over 1 hour on days 21-23. Treatment repeats every 42 days for 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 3, 6, 9, 12, 16, 20, 24, 36, 48, 60, and 72 months.

Study Design

Study Type:
Interventional
Actual Enrollment :
26 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Study for the Treatment of Non-metastatic Nodular Desmoplastic Medulloblastoma in Children Less Than 4 Years of Age
Actual Study Start Date :
Apr 22, 2014
Actual Primary Completion Date :
Mar 31, 2018
Anticipated Study Completion Date :
Mar 31, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (combination chemotherapy)

INDUCTION THERAPY: Patients receive vincristine sulfate IV over 1 minute or infused via minibag on days 1, 15, and 29; cyclophosphamide IV over 1 hour on days 1-3; methotrexate IV over 24 hours on days 15 and 29; etoposide IV over 60-120 minutes on days 43-45; and carboplatin IV over 1 hour on days 43-45. Treatment repeats every 63 days for 3 courses in the absence of disease progression or unacceptable toxicity. CONTINUATION THERAPY: Patients receive vincristine sulfate IV over 1 minute or infused via minibag on day 1, cyclophosphamide IV over 1 hour on days 1-3, etoposide IV over 60-120 minutes on days 21-23, and carboplatin IV over 1 hour on days 21-23. Treatment repeats every 42 days for 2 courses in the absence of disease progression or unacceptable toxicity.

Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
  • Other: Cognitive Assessment
    Optional ancillary studies

    Drug: Cyclophosphamide
    Given IV
    Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
  • Drug: Etoposide
    Given IV
    Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16-213
  • VP-16
  • VP-16-213
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Drug: Methotrexate
    Given IV
    Other Names:
  • Abitrexate
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate
  • Mexate-AQ
  • MTX
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039
  • Drug: Vincristine Sulfate
    Given IV
    Other Names:
  • Kyocristine
  • Leurocristine sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate
  • Outcome Measures

    Primary Outcome Measures

    1. Progression-free Survival (PFS) [2 years from diagnosis]

      Progression-free survival (PFS) is defined as the time interval from diagnosis to the earliest of disease progression/recurrence or death from any cause, or to the date of last follow-up for patients without events. PFS was estimated using the method of Kaplan and Meier. 2-year estimates are reported with 95% CI's.

    2. Overall Survival (OS) [Assessed up to 72 months, reported at 2 years from diagnosis]

      Overall Survival (OS) is defined as the time from diagnosis to death from any cause, or to the date of last follow-up for survivors. OS was estimated using the method of Kaplan and Meier. 2-year estimates are reported with 95% CI's, as the data are not mature to 72 months.

    3. Event-free Survival (EFS) [2 years from diagnosis]

      Event-free survival (EFS) is defined as the time from diagnosis to the earliest of disease progression/recurrence, second malignancy or death from any cause, or to the date of last follow-up for patients without events. EFS was estimated using the method of Kaplan and Meier. 2-year estimates are reported with 95% CI's.

    4. Percentage of Patients With Responses at 189 Days [189 days from start of treatment]

      The percentage of patients with complete response (CR) at the end of induction (~189 days) was reported and presented with the associated exact 95% confidence interval.

    5. Percentage of Patients With Responses at 273 Days [273 days from start of treatment]

      The percentage of patients with complete response (CR) at the end of therapy (~273 days) was reported and presented with the associated exact 95% confidence interval.

    Other Outcome Measures

    1. Feasibility of Rapid Central Pathology Screening Review Defined as Success Rate of Timely Central Pathology Review Based on the Expectation That at Least 95% of the Cases Will be Reviewed Within 10 Days [Up to 10 days]

      At the end of the trial the feasibility of such a prescreening process will be assessed by reporting the percentage and the associated confidence interval of cases where the central review was obtained within 10 days from receipt of slides.

    2. Molecular Profile [Up to 2 years]

      Contingency table analysis will be used to examine the association of molecular profile with histology.

    3. Change in Neurocognitive and Adaptive Functioning Assessed Using Full Scale IQ Score (FSIQ) and General Adaptive Composite Score (GAC) [Baseline to up to 60 months]

      Changes will be described via paired tests and confidence intervals both for FSIQ and GAC in order to capture any deterioration over time.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A to 47 Months
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients must be newly diagnosed and have a confirmed histologic diagnosis of nodular desmoplastic (ND) medulloblastoma or medulloblastoma with extensive nodularity (MBEN) from rapid central pathology screening review; please note: patients with Gorlin syndrome are eligible

    • Patient must have negative lumbar cerebrospinal fluid (CSF) cytology (lumbar CSF must be obtained unless medically contraindicated); CSF cytology for staging should be performed preferably no sooner than 14 days post operatively to avoid false positive CSF, ideally, CSF should be obtained between day 14 and day 21 to allow for final staging status before enrollment onto the study; Note: patients with positive CSF cytology obtained prior to 14 days after surgery may have cytology repeated to determine eligibility and final CSF status

    • Patients must have:

    • Pre-operative cranial magnetic resonance imaging (MRI) (recommended with gadolinium) or pre-operative computed tomography (CT) (recommended with contrast)

    • Post-operative cranial MRI with and without gadolinium within 72 hours of surgery

    • Spinal MRI pre-op with and without gadolinium or post-op with and without gadolinium preferably within 72 hours of surgery

    • Patients must be enrolled on study within 31 days of definitive surgical resection at which time tissue is acquired to determine a diagnosis; patients must be enrolled before treatment begins; the date protocol therapy is projected to start must be no later than five (5) calendar days after the date of study enrollment; patients who are started on protocol therapy on a Phase II study prior to study enrollment will be considered ineligible

    • Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2; use Lansky for patients =< 16 years of age

    • Patients must have a life expectancy of >= 8 weeks

    • Patients who are receiving dexamethasone must be on a stable dose for at least 1 week prior to study entry

    • Peripheral absolute neutrophil count (ANC) >= 1000/uL

    • Platelet count >= 100,000/uL (transfusion independent)

    • Hemoglobin >= 10.0 g/dL (may receive red blood cell [RBC] transfusions)

    • 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 mg/dL

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

    • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x upper limit of normal (ULN) for age

    • Central nervous system function defined as:

    • Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled

    • Patients must not be in status, coma or assisted ventilation prior to study enrollment

    Exclusion Criteria:
    • Patients with metastatic disease by either MRI evaluation (brain and spine) or lumbar CSF cytology are not eligible

    • Patients must not have received any prior tumor-directed therapy other than surgical intervention and corticosteroids

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Children's Hospital of Alabama Birmingham Alabama United States 35233
    2 Phoenix Childrens Hospital Phoenix Arizona United States 85016
    3 The University of Arizona Medical Center-University Campus Tucson Arizona United States 85724
    4 Arkansas Children's Hospital Little Rock Arkansas United States 72202-3591
    5 Kaiser Permanente Downey Medical Center Downey California United States 90242
    6 City of Hope Comprehensive Cancer Center Duarte California United States 91010
    7 Loma Linda University Medical Center Loma Linda California United States 92354
    8 Miller Children's and Women's Hospital Long Beach Long Beach California United States 90806
    9 Children's Hospital Los Angeles Los Angeles California United States 90027
    10 Valley Children's Hospital Madera California United States 93636
    11 Children's Hospital and Research Center at Oakland Oakland California United States 94609-1809
    12 Kaiser Permanente-Oakland Oakland California United States 94611
    13 Children's Hospital of Orange County Orange California United States 92868
    14 Sutter Medical Center Sacramento Sacramento California United States 95816
    15 University of California Davis Comprehensive Cancer Center Sacramento California United States 95817
    16 Rady Children's Hospital - San Diego San Diego California United States 92123
    17 UCSF Medical Center-Parnassus San Francisco California United States 94143
    18 UCSF Medical Center-Mission Bay San Francisco California United States 94158
    19 Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center Torrance California United States 90502
    20 Children's Hospital Colorado Aurora Colorado United States 80045
    21 Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center Denver Colorado United States 80218
    22 Connecticut Children's Medical Center Hartford Connecticut United States 06106
    23 Yale University New Haven Connecticut United States 06520
    24 Alfred I duPont Hospital for Children Wilmington Delaware United States 19803
    25 MedStar Georgetown University Hospital Washington District of Columbia United States 20007
    26 Children's National Medical Center Washington District of Columbia United States 20010
    27 Golisano Children's Hospital of Southwest Florida Fort Myers Florida United States 33908
    28 University of Florida Health Science Center - Gainesville Gainesville Florida United States 32610
    29 Memorial Regional Hospital/Joe DiMaggio Children's Hospital Hollywood Florida United States 33021
    30 Nemours Children's Clinic-Jacksonville Jacksonville Florida United States 32207
    31 University of Miami Miller School of Medicine-Sylvester Cancer Center Miami Florida United States 33136
    32 Nicklaus Children's Hospital Miami Florida United States 33155
    33 Florida Hospital Orlando Orlando Florida United States 32803
    34 Arnold Palmer Hospital for Children Orlando Florida United States 32806
    35 UF Cancer Center at Orlando Health Orlando Florida United States 32806
    36 Nemours Children's Hospital Orlando Florida United States 32827
    37 Nemours Children's Clinic - Pensacola Pensacola Florida United States 32504
    38 Johns Hopkins All Children's Hospital Saint Petersburg Florida United States 33701
    39 Saint Joseph's Hospital/Children's Hospital-Tampa Tampa Florida United States 33607
    40 Saint Mary's Hospital West Palm Beach Florida United States 33407
    41 Children's Healthcare of Atlanta - Egleston Atlanta Georgia United States 30322
    42 Augusta University Medical Center Augusta Georgia United States 30912
    43 Memorial Health University Medical Center Savannah Georgia United States 31404
    44 Saint Luke's Mountain States Tumor Institute Boise Idaho United States 83712
    45 Lurie Children's Hospital-Chicago Chicago Illinois United States 60611
    46 University of Illinois Chicago Illinois United States 60612
    47 University of Chicago Comprehensive Cancer Center Chicago Illinois United States 60637
    48 Loyola University Medical Center Maywood Illinois United States 60153
    49 Advocate Children's Hospital-Oak Lawn Oak Lawn Illinois United States 60453
    50 Advocate Children's Hospital-Park Ridge Park Ridge Illinois United States 60068
    51 Saint Jude Midwest Affiliate Peoria Illinois United States 61637
    52 Southern Illinois University School of Medicine Springfield Illinois United States 62702
    53 Riley Hospital for Children Indianapolis Indiana United States 46202
    54 Saint Vincent Hospital and Health Care Center Indianapolis Indiana United States 46260
    55 Blank Children's Hospital Des Moines Iowa United States 50309
    56 University of Iowa/Holden Comprehensive Cancer Center Iowa City Iowa United States 52242
    57 University of Kentucky/Markey Cancer Center Lexington Kentucky United States 40536
    58 Norton Children's Hospital Louisville Kentucky United States 40202
    59 Children's Hospital New Orleans New Orleans Louisiana United States 70118
    60 Ochsner Medical Center Jefferson New Orleans Louisiana United States 70121
    61 Eastern Maine Medical Center Bangor Maine United States 04401
    62 Maine Children's Cancer Program Scarborough Maine United States 04074
    63 Sinai Hospital of Baltimore Baltimore Maryland United States 21215
    64 Johns Hopkins University/Sidney Kimmel Cancer Center Baltimore Maryland United States 21287
    65 Walter Reed National Military Medical Center Bethesda Maryland United States 20889-5600
    66 University of Massachusetts Medical School Worcester Massachusetts United States 01655
    67 C S Mott Children's Hospital Ann Arbor Michigan United States 48109
    68 Wayne State University/Karmanos Cancer Institute Detroit Michigan United States 48201
    69 Ascension Saint John Hospital Detroit Michigan United States 48236
    70 Michigan State University Clinical Center East Lansing Michigan United States 48824-7016
    71 Hurley Medical Center Flint Michigan United States 48503
    72 Helen DeVos Children's Hospital at Spectrum Health Grand Rapids Michigan United States 49503
    73 Bronson Methodist Hospital Kalamazoo Michigan United States 49007
    74 Beaumont Children's Hospital-Royal Oak Royal Oak Michigan United States 48073
    75 Children's Hospitals and Clinics of Minnesota - Minneapolis Minneapolis Minnesota United States 55404
    76 University of Minnesota/Masonic Cancer Center Minneapolis Minnesota United States 55455
    77 Mayo Clinic Rochester Minnesota United States 55905
    78 University of Mississippi Medical Center Jackson Mississippi United States 39216
    79 Columbia Regional Columbia Missouri United States 65201
    80 Children's Mercy Hospitals and Clinics Kansas City Missouri United States 64108
    81 Cardinal Glennon Children's Medical Center Saint Louis Missouri United States 63104
    82 Washington University School of Medicine Saint Louis Missouri United States 63110
    83 Mercy Hospital Saint Louis Saint Louis Missouri United States 63141
    84 Children's Hospital and Medical Center of Omaha Omaha Nebraska United States 68114
    85 University of Nebraska Medical Center Omaha Nebraska United States 68198
    86 Sunrise Hospital and Medical Center Las Vegas Nevada United States 89109
    87 Alliance for Childhood Diseases/Cure 4 the Kids Foundation Las Vegas Nevada United States 89135
    88 Dartmouth Hitchcock Medical Center Lebanon New Hampshire United States 03756
    89 Hackensack University Medical Center Hackensack New Jersey United States 07601
    90 Morristown Medical Center Morristown New Jersey United States 07960
    91 Saint Peter's University Hospital New Brunswick New Jersey United States 08901
    92 Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital New Brunswick New Jersey United States 08903
    93 Newark Beth Israel Medical Center Newark New Jersey United States 07112
    94 Saint Joseph's Regional Medical Center Paterson New Jersey United States 07503
    95 University of New Mexico Cancer Center Albuquerque New Mexico United States 87102
    96 Albany Medical Center Albany New York United States 12208
    97 Montefiore Medical Center - Moses Campus Bronx New York United States 10467
    98 Roswell Park Cancer Institute Buffalo New York United States 14263
    99 NYU Winthrop Hospital Mineola New York United States 11501
    100 The Steven and Alexandra Cohen Children's Medical Center of New York New Hyde Park New York United States 11040
    101 Laura and Isaac Perlmutter Cancer Center at NYU Langone New York New York United States 10016
    102 Mount Sinai Hospital New York New York United States 10029
    103 Columbia University/Herbert Irving Cancer Center New York New York United States 10032
    104 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    105 University of Rochester Rochester New York United States 14642
    106 State University of New York Upstate Medical University Syracuse New York United States 13210
    107 New York Medical College Valhalla New York United States 10595
    108 Mission Hospital Inc-Memorial Campus Asheville North Carolina United States 28801
    109 UNC Lineberger Comprehensive Cancer Center Chapel Hill North Carolina United States 27599
    110 Wake Forest University Health Sciences Winston-Salem North Carolina United States 27157
    111 Sanford Broadway Medical Center Fargo North Dakota United States 58122
    112 Children's Hospital Medical Center of Akron Akron Ohio United States 44308
    113 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229
    114 Rainbow Babies and Childrens Hospital Cleveland Ohio United States 44106
    115 Cleveland Clinic Foundation Cleveland Ohio United States 44195
    116 Nationwide Children's Hospital Columbus Ohio United States 43205
    117 Dayton Children's Hospital Dayton Ohio United States 45404
    118 The Toledo Hospital/Toledo Children's Hospital Toledo Ohio United States 43606
    119 University of Oklahoma Health Sciences Center Oklahoma City Oklahoma United States 73104
    120 Legacy Emanuel Children's Hospital Portland Oregon United States 97227
    121 Oregon Health and Science University Portland Oregon United States 97239
    122 Geisinger Medical Center Danville Pennsylvania United States 17822
    123 Penn State Children's Hospital Hershey Pennsylvania United States 17033
    124 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    125 Saint Christopher's Hospital for Children Philadelphia Pennsylvania United States 19134
    126 Children's Hospital of Pittsburgh of UPMC Pittsburgh Pennsylvania United States 15224
    127 Rhode Island Hospital Providence Rhode Island United States 02903
    128 Medical University of South Carolina Charleston South Carolina United States 29425
    129 Palmetto Health Richland Columbia South Carolina United States 29203
    130 BI-LO Charities Children's Cancer Center Greenville South Carolina United States 29605
    131 Sanford USD Medical Center - Sioux Falls Sioux Falls South Dakota United States 57117-5134
    132 T C Thompson Children's Hospital Chattanooga Tennessee United States 37403
    133 East Tennessee Childrens Hospital Knoxville Tennessee United States 37916
    134 St. Jude Children's Research Hospital Memphis Tennessee United States 38105
    135 Vanderbilt University/Ingram Cancer Center Nashville Tennessee United States 37232
    136 Dell Children's Medical Center of Central Texas Austin Texas United States 78723
    137 Driscoll Children's Hospital Corpus Christi Texas United States 78411
    138 Medical City Dallas Hospital Dallas Texas United States 75230
    139 UT Southwestern/Simmons Cancer Center-Dallas Dallas Texas United States 75390
    140 El Paso Children's Hospital El Paso Texas United States 79905
    141 Cook Children's Medical Center Fort Worth Texas United States 76104
    142 Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center Houston Texas United States 77030
    143 Children's Hospital of San Antonio San Antonio Texas United States 78207
    144 Methodist Children's Hospital of South Texas San Antonio Texas United States 78229
    145 University of Texas Health Science Center at San Antonio San Antonio Texas United States 78229
    146 Scott and White Memorial Hospital Temple Texas United States 76508
    147 Primary Children's Hospital Salt Lake City Utah United States 84113
    148 University of Vermont College of Medicine Burlington Vermont United States 05405
    149 Inova Fairfax Hospital Falls Church Virginia United States 22042
    150 Children's Hospital of The King's Daughters Norfolk Virginia United States 23507
    151 Virginia Commonwealth University/Massey Cancer Center Richmond Virginia United States 23298
    152 Carilion Clinic Children's Hospital Roanoke Virginia United States 24014
    153 Seattle Children's Hospital Seattle Washington United States 98105
    154 Providence Sacred Heart Medical Center and Children's Hospital Spokane Washington United States 99204
    155 Mary Bridge Children's Hospital and Health Center Tacoma Washington United States 98405
    156 West Virginia University Healthcare Morgantown West Virginia United States 26506
    157 Marshfield Medical Center-Marshfield Marshfield Wisconsin United States 54449
    158 Children's Hospital of Wisconsin Milwaukee Wisconsin United States 53226
    159 John Hunter Children's Hospital Hunter Regional Mail Centre New South Wales Australia 2310
    160 Women's and Children's Hospital-Adelaide North Adelaide South Australia Australia 5006
    161 Princess Margaret Hospital for Children Perth Western Australia Australia 6008
    162 Alberta Children's Hospital Calgary Alberta Canada T3B 6A8
    163 British Columbia Children's Hospital Vancouver British Columbia Canada V6H 3V4
    164 CancerCare Manitoba Winnipeg Manitoba Canada R3E 0V9
    165 Janeway Child Health Centre Saint John's Newfoundland and Labrador Canada A1B 3V6
    166 IWK Health Centre Halifax Nova Scotia Canada B3K 6R8
    167 McMaster Children's Hospital at Hamilton Health Sciences Hamilton Ontario Canada L8N 3Z5
    168 Hospital for Sick Children Toronto Ontario Canada M5G 1X8
    169 The Montreal Children's Hospital of the MUHC Montreal Quebec Canada H3H 1P3
    170 Centre Hospitalier Universitaire Sainte-Justine Montreal Quebec Canada H3T 1C5
    171 Centre Hospitalier Universitaire de Quebec Quebec Canada G1V 4G2
    172 San Jorge Children's Hospital San Juan Puerto Rico 00912
    173 University Pediatric Hospital San Juan Puerto Rico 00926

    Sponsors and Collaborators

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

    Investigators

    • Principal Investigator: Lucie E Lafay-Cousin, Children's Oncology Group

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Children's Oncology Group
    ClinicalTrials.gov Identifier:
    NCT02017964
    Other Study ID Numbers:
    • ACNS1221
    • NCI-2013-02379
    • ACNS1221
    • COG-ACNS1221
    • s15-00476
    • ACNS1221
    • ACNS1221
    • U10CA180886
    • U10CA098543
    First Posted:
    Dec 23, 2013
    Last Update Posted:
    Jan 13, 2022
    Last Verified:
    Jan 1, 2022

    Study Results

    Participant Flow

    Recruitment Details This study opened for entry on December 24, 2013, and the first patient was enrolled on April 22, 2014. The study enrolled 26 patients before being closed early due to inferior efficacy as of July 27, 2016. 25 of the 26 patients enrolled were deemed to be eligible
    Pre-assignment Detail
    Arm/Group Title All Patients (Combination Chemotherapy)
    Arm/Group Description All patients enrolled on the study. Patients received 3-5 cycles of therapy which included cyclophosphamide (800 mg/m2/day), vincristine (1.5 mg/m2/day), methotrexate (5,000 mg/m2), etoposide (150 mg/m2/dose) and carboplatin (200 mg/m2/day IV).
    Period Title: Overall Study
    STARTED 26
    COMPLETED 25
    NOT COMPLETED 1

    Baseline Characteristics

    Arm/Group Title All Eligible Patients (Combination Chemotherapy)
    Arm/Group Description All eligible patients enrolled on the study
    Overall Participants 26
    Age (Count of Participants)
    <=18 years
    26
    100%
    Between 18 and 65 years
    0
    0%
    >=65 years
    0
    0%
    Age (months (at time of dx)) [Median (Full Range) ]
    Median (Full Range) [months (at time of dx)]
    19.7
    Sex: Female, Male (Count of Participants)
    Female
    10
    38.5%
    Male
    16
    61.5%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    6
    23.1%
    Not Hispanic or Latino
    19
    73.1%
    Unknown or Not Reported
    1
    3.8%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    1
    3.8%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    2
    7.7%
    White
    20
    76.9%
    More than one race
    0
    0%
    Unknown or Not Reported
    3
    11.5%
    Region of Enrollment (participants) [Number]
    United States
    23
    88.5%
    Canada
    3
    11.5%

    Outcome Measures

    1. Primary Outcome
    Title Progression-free Survival (PFS)
    Description Progression-free survival (PFS) is defined as the time interval from diagnosis to the earliest of disease progression/recurrence or death from any cause, or to the date of last follow-up for patients without events. PFS was estimated using the method of Kaplan and Meier. 2-year estimates are reported with 95% CI's.
    Time Frame 2 years from diagnosis

    Outcome Measure Data

    Analysis Population Description
    26 patients were enrolled on the protocol, but 1 was deemed ineligible. The ineligible patient was excluded from all analyses.
    Arm/Group Title All Eligible Patients (Combination Chemotherapy)
    Arm/Group Description All eligible patients enrolled on the study
    Measure Participants 25
    Number (95% Confidence Interval) [percent probability]
    52.0
    2. Primary Outcome
    Title Overall Survival (OS)
    Description Overall Survival (OS) is defined as the time from diagnosis to death from any cause, or to the date of last follow-up for survivors. OS was estimated using the method of Kaplan and Meier. 2-year estimates are reported with 95% CI's, as the data are not mature to 72 months.
    Time Frame Assessed up to 72 months, reported at 2 years from diagnosis

    Outcome Measure Data

    Analysis Population Description
    26 patients were enrolled on the protocol, but 1 was deemed ineligible. The ineligible patient was excluded from all analyses.
    Arm/Group Title All Eligible Patients (Combination Chemotherapy)
    Arm/Group Description All eligible patients enrolled on the study
    Measure Participants 25
    Number (95% Confidence Interval) [percent probability]
    92.0
    3. Primary Outcome
    Title Event-free Survival (EFS)
    Description Event-free survival (EFS) is defined as the time from diagnosis to the earliest of disease progression/recurrence, second malignancy or death from any cause, or to the date of last follow-up for patients without events. EFS was estimated using the method of Kaplan and Meier. 2-year estimates are reported with 95% CI's.
    Time Frame 2 years from diagnosis

    Outcome Measure Data

    Analysis Population Description
    26 patients were enrolled on the protocol, but 1 was deemed ineligible. The ineligible patient is excluded from all analyses.
    Arm/Group Title All Eligible Patients (Combination Chemotherapy)
    Arm/Group Description All eligible patients enrolled on the study
    Measure Participants 25
    Number (95% Confidence Interval) [percent probability]
    52.0
    4. Primary Outcome
    Title Percentage of Patients With Responses at 189 Days
    Description The percentage of patients with complete response (CR) at the end of induction (~189 days) was reported and presented with the associated exact 95% confidence interval.
    Time Frame 189 days from start of treatment

    Outcome Measure Data

    Analysis Population Description
    26 patients were enrolled on the protocol, but 1 was deemed ineligible. The ineligible patient was excluded from all analyses.
    Arm/Group Title All Eligible Patients (Combination Chemotherapy)
    Arm/Group Description All eligible patients enrolled on the study
    Measure Participants 25
    Number (95% Confidence Interval) [Percentage of patients]
    92.0
    5. Primary Outcome
    Title Percentage of Patients With Responses at 273 Days
    Description The percentage of patients with complete response (CR) at the end of therapy (~273 days) was reported and presented with the associated exact 95% confidence interval.
    Time Frame 273 days from start of treatment

    Outcome Measure Data

    Analysis Population Description
    26 patients were enrolled on the protocol, but 1 was deemed ineligible. The ineligible patient is excluded from all analyses.
    Arm/Group Title All Eligible Patients (Combination Chemotherapy)
    Arm/Group Description All eligible patients enrolled on the study
    Measure Participants 25
    Number (95% Confidence Interval) [Percentage of patients]
    88.0
    6. Other Pre-specified Outcome
    Title Feasibility of Rapid Central Pathology Screening Review Defined as Success Rate of Timely Central Pathology Review Based on the Expectation That at Least 95% of the Cases Will be Reviewed Within 10 Days
    Description At the end of the trial the feasibility of such a prescreening process will be assessed by reporting the percentage and the associated confidence interval of cases where the central review was obtained within 10 days from receipt of slides.
    Time Frame Up to 10 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    7. Other Pre-specified Outcome
    Title Molecular Profile
    Description Contingency table analysis will be used to examine the association of molecular profile with histology.
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    8. Other Pre-specified Outcome
    Title Change in Neurocognitive and Adaptive Functioning Assessed Using Full Scale IQ Score (FSIQ) and General Adaptive Composite Score (GAC)
    Description Changes will be described via paired tests and confidence intervals both for FSIQ and GAC in order to capture any deterioration over time.
    Time Frame Baseline to up to 60 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time Frame 1 year
    Adverse Event Reporting Description Adverse event reporting is collected routinely using case report forms. SAE field contains NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients are excluded from reporting of adverse events.
    Arm/Group Title All Eligible Patients (Combination Chemotherapy)
    Arm/Group Description All eligible patients enrolled on the study
    All Cause Mortality
    All Eligible Patients (Combination Chemotherapy)
    Affected / at Risk (%) # Events
    Total 2/25 (8%)
    Serious Adverse Events
    All Eligible Patients (Combination Chemotherapy)
    Affected / at Risk (%) # Events
    Total 2/25 (8%)
    General disorders
    Death NOS 1/25 (4%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Other, Progression Of Medulloblastoma 1/25 (4%) 1
    Other (Not Including Serious) Adverse Events
    All Eligible Patients (Combination Chemotherapy)
    Affected / at Risk (%) # Events
    Total 17/25 (68%)
    Blood and lymphatic system disorders
    Febrile neutropenia 1/25 (4%) 1
    Leukocytosis 1/25 (4%) 4
    Ear and labyrinth disorders
    Hearing impaired 1/25 (4%) 1
    Infections and infestations
    Meningitis 1/25 (4%) 1
    Investigations
    Lymphocyte count decreased 7/25 (28%) 18
    Neutrophil count decreased 14/25 (56%) 36
    Platelet count decreased 7/25 (28%) 13
    White blood cell decreased 11/25 (44%) 24
    Metabolism and nutrition disorders
    Hypernatremia 1/25 (4%) 1
    Hypokalemia 1/25 (4%) 1

    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 626-446-0064
    Email resultsreportingcoordinator@childrensoncologygroup.org
    Responsible Party:
    Children's Oncology Group
    ClinicalTrials.gov Identifier:
    NCT02017964
    Other Study ID Numbers:
    • ACNS1221
    • NCI-2013-02379
    • ACNS1221
    • COG-ACNS1221
    • s15-00476
    • ACNS1221
    • ACNS1221
    • U10CA180886
    • U10CA098543
    First Posted:
    Dec 23, 2013
    Last Update Posted:
    Jan 13, 2022
    Last Verified:
    Jan 1, 2022