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Vorinostat and Radiation Therapy Followed by Maintenance Therapy With Vorinostat in Treating Younger Patients With Newly Diagnosed Diffuse Intrinsic Pontine Glioma

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT01189266
Collaborator
(none)
79
Enrollment
180
Locations
3
Arms
133.7
Actual Duration (Months)
0.4
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase I/II trial studies the side effects and best dose of vorinostat and to see how well it works when given together with radiation therapy followed by maintenance therapy with vorinostat in treating younger patients with newly diagnosed diffuse intrinsic pontine glioma (a brainstem tumor). Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving vorinostat together with radiation therapy may kill more tumor cells.

Condition or Disease Intervention/Treatment Phase
  • Radiation: 3-Dimensional Conformal Radiation Therapy
  • Radiation: Intensity-Modulated Radiation Therapy
  • Other: Laboratory Biomarker Analysis
  • Drug: Vorinostat
 Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. To estimate the maximum tolerated dose (MTD) or recommend a phase 2 dose of vorinostat given concurrently with radiation in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG).

  1. To define and describe the toxicities of vorinostat given concurrently with radiation in children with newly diagnosed DIPG.

  2. To determine, in the context of this phase I/II trial, the anti-tumor activity of combining vorinostat with radiation, followed by maintenance vorinostat for twelve courses, in children with newly diagnosed DIPG, as measured by 12-month event-free survival (EFS) and overall survival (OS).

  3. To determine the toxicities of vorinostat for 12 additional courses after completion of vorinostat and radiation.

SECONDARY OBJECTIVES:

  1. To measure non-homologous end-joining (NHEJ) activity in peripheral blood mononuclear cells (PBMCs) before treatment, at 2 weeks after starting vorinostat and radiation, and at the end of radiation.

  2. To measure histone deacetylase 2 (HDAC2) levels and assess histone acetylation in PBMCs before treatment, at 2 weeks after starting vorinostat and radiation, and at the end of radiation.

  3. To quantify deoxyribonucleic acid (DNA) repair proteins from the NHEJ and homologous recombination repair (HHR) pathways in tumors by either Western analysis or immunohistochemistry, if paraffin-embedded tumor is available.

OUTLINE: This is a phase I, dose-escalation study of vorinostat followed by a phase II study.

Patients receive vorinostat orally (PO) on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients undergo 3-dimensional (3D) conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. Patients then receive maintenance therapy comprising vorinostat PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months.

Study Design

Study Type:
Interventional
Actual Enrollment :
79 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2 Study of Suberoylanilide Hydroxamic Acid (SAHA, Vorinostat) and Local Irradiation, Followed by Maintenance SAHA in Children With Newly Diagnosed Diffuse Intrinsic Pontine Gliomas (DIPG)
Actual Study Start Date :
Aug 9, 2010
Actual Primary Completion Date :
Jun 30, 2017
Actual Study Completion Date :
Sep 30, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm 1 Phase I Vorinostat 180 mg/m^2

Patients in phase I received vorinostat at 180 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Radiation: 3-Dimensional Conformal Radiation Therapy
Undergo 3D conformal radiation therapy
Other Names:
  • 3-dimensional radiation therapy
  • 3D Conformal
  • 3D CONFORMAL RADIATION THERAPY
  • 3D CRT
  • 3D-CRT
  • Conformal Therapy
  • Radiation Conformal Therapy
  • Radiation, 3D Conformal

    • Radiation: Intensity-Modulated Radiation Therapy
    Undergo intensity-modulated radiation therapy
    Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy
  • Radiation, Intensity-Modulated Radiotherapy

    • Other: Laboratory Biomarker Analysis
    Correlative studies

    Drug: Vorinostat
    Given PO
    Other Names:
  • L-001079038
  • MSK-390
  • SAHA
  • Suberanilohydroxamic Acid
  • Suberoylanilide Hydroxamic Acid
  • Zolinza

    		•
    Experimental: Arm 2 Phase 1 Vorinostat 230 mg/m^2

    Patients received a higher dose of vorinostat at 230 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

    Radiation: 3-Dimensional Conformal Radiation Therapy
    Undergo 3D conformal radiation therapy
    Other Names:
  • 3-dimensional radiation therapy
  • 3D Conformal
  • 3D CONFORMAL RADIATION THERAPY
  • 3D CRT
  • 3D-CRT
  • Conformal Therapy
  • Radiation Conformal Therapy
  • Radiation, 3D Conformal

    • Radiation: Intensity-Modulated Radiation Therapy
    Undergo intensity-modulated radiation therapy
    Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy
  • Radiation, Intensity-Modulated Radiotherapy

    • Other: Laboratory Biomarker Analysis
    Correlative studies

    Drug: Vorinostat
    Given PO
    Other Names:
  • L-001079038
  • MSK-390
  • SAHA
  • Suberanilohydroxamic Acid
  • Suberoylanilide Hydroxamic Acid
  • Zolinza

    		•
    Experimental: Arm 3 Phase II Evaluation Vorinostat 230 mg/m^2

    Patients received a higher dose of vorinostat at 230 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/ day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

    Radiation: 3-Dimensional Conformal Radiation Therapy
    Undergo 3D conformal radiation therapy
    Other Names:
  • 3-dimensional radiation therapy
  • 3D Conformal
  • 3D CONFORMAL RADIATION THERAPY
  • 3D CRT
  • 3D-CRT
  • Conformal Therapy
  • Radiation Conformal Therapy
  • Radiation, 3D Conformal

    • Radiation: Intensity-Modulated Radiation Therapy
    Undergo intensity-modulated radiation therapy
    Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy
  • Radiation, Intensity-Modulated Radiotherapy

    • Other: Laboratory Biomarker Analysis
    Correlative studies

    Drug: Vorinostat
    Given PO
    Other Names:
  • L-001079038
  • MSK-390
  • SAHA
  • Suberanilohydroxamic Acid
  • Suberoylanilide Hydroxamic Acid
  • Zolinza

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Maximum Tolerated Dose (MTD) of Vorinostat [Planned 7 weeks during chemoradiotherapy]

      The dose of vorinostat in mg/sqm/day to be administered with combination chemotherapy and radiation therapy

    2. Event-Free Survival [2 years after study enrollment]

      Time from enrollment to disease progression, diagnosis of a second malignant neoplasm, death or last follow-up, whichever occurs first.

    3. Incidence of Toxicity During Chemoradiation Therapy [Planned 7 weeks during chemoradiotherapy]

      Proportion of patients who experience any grade 3 or higher CTC AE Version 4 adverse experience

    4. Incidence of Toxicity During Maintenance Therapy [Planned 12 months of maintenance with Vorinostat]

      Proportion of patients who experience any grade 3 or higher CTC AE Version 4 adverse experience

    Secondary Outcome Measures

    1. Overall Survival [2 years after study enrollment]

      Time from enrollment to death or last follow-up, whichever occurs first.

    2. Change in H3 and H4 Acetylation Levels in PBMCs [Baseline to up to 7 weeks]

      Degree of acetylation in peripheral blood monocytes will be divided into quartiles and coded as none, mild, moderation or marked.

    3. Change in NHEJ Activity in PBMCs [Baseline to up to 7 weeks]

      Descriptive statistics will be used to summarize the biological/laboratory measures and the changes in these measures across time-points.

    4. Levels of DNA Repair Proteins in Paraffin-embedded Blocks, Measured Via Immunohistochemistry or Western Analysis [Baseline]

      For immunohistochemistry from tumor blocks, the intensity will be graded from 1 to 3; for Western analysis, a percentage of the intensity relative to the tumor with the highest level will be measured.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    37 Months to 21 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Patients with newly diagnosed diffuse intrinsic pontine gliomas (DIPGs), defined as tumors with a pontine epicenter and diffuse involvement of at least 2/3 of the pons, are eligible without histologic confirmation; patients with brainstem tumors that do not meet these criteria or not considered to be typical intrinsic pontine gliomas will only be eligible if the tumors are biopsied and proven to be an anaplastic astrocytoma, glioblastoma multiforme, gliosarcoma, or anaplastic mixed glioma; patients with juvenile pilocytic astrocytoma, fibrillary astrocytoma, gangliogliomas, or other mixed gliomas without anaplasia are not eligible; patients with disseminated disease are not eligible, and magnetic resonance imaging (MRI) of spine must be performed if disseminated disease is suspected by the treating physician

    • Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score

    • Patients must not have received any prior treatment except dexamethasone and/or surgery

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

    • Platelet count >= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment)

    • Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions)

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

    • 0.8 mg/dL (3 to < 6 years of age)

    • 1 mg/dL (6 to < 10 years of age)

    • 1.2 mg/dL (10 to < 13 years of age)

    • 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)

    • 1.7 mg/dL (male) or 1.4 mg/dL (female) (>= 16 years of age)

    • Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age

    • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 U/L; for the purpose of this study, the ULN for SGPT (ALT) is 45 U/L

    • Serum albumin >= 2 g/dL

    • Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants (with the exception of valproic acid) and seizures are well controlled

    • Patients must be able to swallow capsules or liquids; patients dependent on nasogastric (NG) tube feeding are not permitted to receive protocol therapy

    • Enrollment must be no later than 28 days after the date of radiographic diagnosis or surgery, whichever is the later date

    Exclusion Criteria:

    • Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method

    • Growth factors that support platelet or white cell number or function must not have been administered within the 7 days prior to enrollment

    • Patients who are currently receiving another investigational drug are not eligible

    • Patients who are currently receiving other anti-cancer agents are not eligible

    • Patients must not currently be receiving enzyme inducing anticonvulsants

    • Patients on valproic acid must discontinue valproic acid for at least 2 weeks before starting protocol therapy

    • Patients receiving coumadin, heparin, low-molecular weight heparin, or any other anti-coagulants are not eligible for study entry

    • Patients receiving acetylsalicylic acid (ASA) (> 81 mg/day), non-steroidal anti-inflammatory drugs, clopidogrel (Plavix), dipyridamole (Persantine), or any other drug that inhibits platelet function are not eligible for study entry

    • Patients who have an uncontrolled infection are not eligible

    • Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

    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 Cancer Center Birmingham Alabama United States 35233
    3 Providence Hospital Mobile Alabama United States 36608
    4 Arkansas Children's Hospital Little Rock Arkansas United States 72202-3591
    5 University of Arkansas for Medical Sciences Little Rock Arkansas United States 72205
    6 Highlands Oncology Group Rogers Arkansas United States 72758
    7 Kaiser Permanente-Deer Valley Medical Center Antioch California United States 94531
    8 Kaiser Permanente Downey Medical Center Downey California United States 90242
    9 Kaiser Permanente-Fremont Fremont California United States 94538
    10 Kaiser Permanente-Fresno Fresno California United States 93720
    11 Miller Children's and Women's Hospital Long Beach Long Beach California United States 90806
    12 Cedars Sinai Medical Center Los Angeles California United States 90048
    13 Valley Children's Hospital Madera California United States 93636
    14 Contra Costa Regional Medical Center Martinez California United States 94553-3156
    15 El Camino Hospital Mountain View California United States 94040
    16 Highland General Hospital Oakland California United States 94602
    17 Alta Bates Summit Medical Center - Summit Campus Oakland California United States 94609
    18 Bay Area Tumor Institute Oakland California United States 94609
    19 UCSF Benioff Children's Hospital Oakland Oakland California United States 94609
    20 Kaiser Permanente-Oakland Oakland California United States 94611
    21 Children's Hospital of Orange County Orange California United States 92868
    22 Kaiser Permanente-Redwood City Redwood City California United States 94063
    23 Kaiser Permanente-Richmond Richmond California United States 94801
    24 Kaiser Permanente-Roseville Roseville California United States 95661
    25 Kaiser Permanente-South Sacramento Sacramento California United States 95823
    26 Kaiser Permanente - Sacramento Sacramento California United States 95825
    27 Rady Children's Hospital - San Diego San Diego California United States 92123
    28 Kaiser Permanente-San Francisco San Francisco California United States 94115
    29 UCSF Medical Center-Parnassus San Francisco California United States 94143
    30 UCSF Medical Center-Mission Bay San Francisco California United States 94158
    31 Kaiser Permanente-Santa Teresa-San Jose San Jose California United States 95119
    32 Kaiser Permanente San Leandro San Leandro California United States 94577
    33 Doctors Medical Center- JC Robinson Regional Cancer Center San Pablo California United States 94806
    34 Kaiser Permanente-San Rafael San Rafael California United States 94903
    35 Kaiser Permanente Medical Center - Santa Clara Santa Clara California United States 95051
    36 Kaiser Permanente-Santa Rosa Santa Rosa California United States 95403
    37 Kaiser Permanente-South San Francisco South San Francisco California United States 94080
    38 Kaiser Permanente-Stockton Stockton California United States 95210
    39 Kaiser Permanente Medical Center-Vacaville Vacaville California United States 95688
    40 Kaiser Permanente-Vallejo Vallejo California United States 94589
    41 Kaiser Permanente-Walnut Creek Walnut Creek California United States 94596
    42 Children's Hospital Colorado Aurora Colorado United States 80045
    43 Smilow Cancer Hospital Care Center at Saint Francis Hartford Connecticut United States 06105
    44 Alfred I duPont Hospital for Children Wilmington Delaware United States 19803
    45 Children's National Medical Center Washington District of Columbia United States 20010
    46 Lee Memorial Health System Fort Myers Florida United States 33901
    47 Golisano Children's Hospital of Southwest Florida Fort Myers Florida United States 33908
    48 Nemours Children's Clinic-Jacksonville Jacksonville Florida United States 32207
    49 AdventHealth Orlando Orlando Florida United States 32803
    50 Arnold Palmer Hospital for Children Orlando Florida United States 32806
    51 Nemours Children's Clinic - Orlando Orlando Florida United States 32806
    52 Orlando Health Cancer Institute Orlando Florida United States 32806
    53 Nemours Children's Hospital Orlando Florida United States 32827
    54 Nemours Children's Clinic - Pensacola Pensacola Florida United States 32504
    55 Johns Hopkins All Children's Hospital Saint Petersburg Florida United States 33701
    56 Children's Healthcare of Atlanta - Egleston Atlanta Georgia United States 30322
    57 Memorial Health University Medical Center Savannah Georgia United States 31404
    58 University of Hawaii Cancer Center Honolulu Hawaii United States 96813
    59 Kaiser Permanente Moanalua Medical Center Honolulu Hawaii United States 96819
    60 Saint Alphonsus Cancer Care Center-Boise Boise Idaho United States 83706
    61 Saint Anthony's Health Alton Illinois United States 62002
    62 Lurie Children's Hospital-Chicago Chicago Illinois United States 60611
    63 Decatur Memorial Hospital Decatur Illinois United States 62526
    64 Loyola University Medical Center Maywood Illinois United States 60153
    65 Good Samaritan Regional Health Center Mount Vernon Illinois United States 62864
    66 Edward Hospital/Cancer Center Naperville Illinois United States 60540
    67 Saint Jude Midwest Affiliate Peoria Illinois United States 61637
    68 Memorial Medical Center Springfield Illinois United States 62781
    69 Riley Hospital for Children Indianapolis Indiana United States 46202
    70 Blank Children's Hospital Des Moines Iowa United States 50309
    71 Baptist Health Lexington Lexington Kentucky United States 40503
    72 University of Kentucky/Markey Cancer Center Lexington Kentucky United States 40536
    73 Norton Children's Hospital Louisville Kentucky United States 40202
    74 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
    75 Michigan Cancer Research Consortium NCORP Ann Arbor Michigan United States 48106
    76 Saint Joseph Mercy Hospital Ann Arbor Michigan United States 48106
    77 C S Mott Children's Hospital Ann Arbor Michigan United States 48109
    78 Beaumont Hospital - Dearborn Dearborn Michigan United States 48124
    79 Ascension Saint John Hospital Detroit Michigan United States 48236
    80 Hurley Medical Center Flint Michigan United States 48503
    81 Genesys Regional Medical Center-West Flint Campus Flint Michigan United States 48532
    82 Helen DeVos Children's Hospital at Spectrum Health Grand Rapids Michigan United States 49503
    83 Allegiance Health Jackson Michigan United States 49201
    84 Sparrow Hospital Lansing Michigan United States 48912
    85 Saint Mary Mercy Hospital Livonia Michigan United States 48154
    86 Saint Joseph Mercy Oakland Pontiac Michigan United States 48341
    87 Lake Huron Medical Center Port Huron Michigan United States 48060
    88 Ascension Saint Mary's Hospital Saginaw Michigan United States 48601
    89 Saint John Macomb-Oakland Hospital Warren Michigan United States 48093
    90 University of Minnesota/Masonic Cancer Center Minneapolis Minnesota United States 55455
    91 University of Mississippi Medical Center Jackson Mississippi United States 39216
    92 Singing River Hospital Pascagoula Mississippi United States 39581
    93 Saint Francis Medical Center Cape Girardeau Missouri United States 63703
    94 Children's Mercy Hospitals and Clinics Kansas City Missouri United States 64108
    95 Cardinal Glennon Children's Medical Center Saint Louis Missouri United States 63104
    96 Saint Louis Cancer and Breast Institute-South City Saint Louis Missouri United States 63109
    97 Washington University School of Medicine Saint Louis Missouri United States 63110
    98 Saint Louis-Cape Girardeau CCOP Saint Louis Missouri United States 63141
    99 Cancer Research for the Ozarks NCORP Springfield Missouri United States 65804
    100 Mercy Hospital Springfield Springfield Missouri United States 65804
    101 CoxHealth South Hospital Springfield Missouri United States 65807
    102 Billings Clinic Cancer Center Billings Montana United States 59101
    103 Saint Vincent Healthcare Billings Montana United States 59101
    104 Montana Cancer Consortium NCORP Billings Montana United States 59102
    105 Saint Vincent Frontier Cancer Center Billings Montana United States 59102
    106 Bozeman Deaconess Hospital Bozeman Montana United States 59715
    107 Benefis Healthcare- Sletten Cancer Institute Great Falls Montana United States 59405
    108 Great Falls Clinic Great Falls Montana United States 59405
    109 Saint Peter's Community Hospital Helena Montana United States 59601
    110 Glacier Oncology PLLC Kalispell Montana United States 59901
    111 Kalispell Regional Medical Center Kalispell Montana United States 59901
    112 Saint Patrick Hospital - Community Hospital Missoula Montana United States 59802
    113 CHI Health Good Samaritan Kearney Nebraska United States 68847
    114 Morristown Medical Center Morristown New Jersey United States 07960
    115 Saint Peter's University Hospital New Brunswick New Jersey United States 08901
    116 Newark Beth Israel Medical Center Newark New Jersey United States 07112
    117 Overlook Hospital Summit New Jersey United States 07902
    118 University of New Mexico Cancer Center Albuquerque New Mexico United States 87102
    119 Montefiore Medical Center - Moses Campus Bronx New York United States 10467
    120 Roswell Park Cancer Institute Buffalo New York United States 14263
    121 Laura and Isaac Perlmutter Cancer Center at NYU Langone New York New York United States 10016
    122 NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center New York New York United States 10032
    123 Mission Hospital Asheville North Carolina United States 28801
    124 Carolinas Medical Center/Levine Cancer Institute Charlotte North Carolina United States 28203
    125 Wayne Memorial Hospital Goldsboro North Carolina United States 27534
    126 Margaret R Pardee Memorial Hospital Hendersonville North Carolina United States 28791
    127 Iredell Memorial Hospital Statesville North Carolina United States 28677
    128 Southeast Clinical Oncology Research Consortium NCORP Winston-Salem North Carolina United States 27104
    129 Wake Forest University Health Sciences Winston-Salem North Carolina United States 27157
    130 Cleveland Clinic Akron General Akron Ohio United States 44307
    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 Nationwide Children's Hospital Columbus Ohio United States 43205
    134 Saint Charles Health System Bend Oregon United States 97701
    135 Legacy Emanuel Children's Hospital Portland Oregon United States 97227
    136 Oregon Health and Science University Portland Oregon United States 97239
    137 Penn State Children's Hospital Hershey Pennsylvania United States 17033
    138 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    139 AnMed Health Hospital Anderson South Carolina United States 29621
    140 Prisma Health Richland Hospital Columbia South Carolina United States 29203
    141 Saint Francis Hospital Greenville South Carolina United States 29601
    142 BI-LO Charities Children's Cancer Center Greenville South Carolina United States 29605
    143 Greenville Cancer Treatment Center Greenville South Carolina United States 29605
    144 Carolina Blood and Cancer Care Associates PA-Lancaster Lancaster South Carolina United States 29720
    145 Spartanburg Medical Center Spartanburg South Carolina United States 29303
    146 Saint Jude Children's Research Hospital Memphis Tennessee United States 38105
    147 Vanderbilt University/Ingram Cancer Center Nashville Tennessee United States 37232
    148 Driscoll Children's Hospital Corpus Christi Texas United States 78411
    149 Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center Houston Texas United States 77030
    150 Methodist Children's Hospital of South Texas San Antonio Texas United States 78229
    151 Primary Children's Hospital Salt Lake City Utah United States 84113
    152 Children's Hospital of The King's Daughters Norfolk Virginia United States 23507
    153 Cancer Care Center at Island Hospital Anacortes Washington United States 98221
    154 PeaceHealth Saint Joseph Medical Center Bellingham Washington United States 98225
    155 Harrison HealthPartners Hematology and Oncology-Bremerton Bremerton Washington United States 98310
    156 Highline Medical Center-Main Campus Burien Washington United States 98166
    157 Kadlec Clinic Hematology and Oncology Kennewick Washington United States 99336
    158 Skagit Valley Hospital Mount Vernon Washington United States 98274
    159 Harrison HealthPartners Hematology and Oncology-Poulsbo Poulsbo Washington United States 98370
    160 Harborview Medical Center Seattle Washington United States 98104
    161 Minor and James Medical PLLC Seattle Washington United States 98104
    162 Seattle Children's Hospital Seattle Washington United States 98105
    163 Fred Hutchinson Cancer Research Center Seattle Washington United States 98109
    164 Kaiser Permanente Washington Seattle Washington United States 98112
    165 Swedish Medical Center-First Hill Seattle Washington United States 98122-4307
    166 University of Washington Medical Center - Montlake Seattle Washington United States 98195
    167 PeaceHealth United General Medical Center Sedro-Woolley Washington United States 98284
    168 Cancer Care Northwest - Spokane South Spokane Washington United States 99202
    169 Evergreen Hematology and Oncology PS Spokane Washington United States 99218
    170 Mary Bridge Children's Hospital and Health Center Tacoma Washington United States 98405
    171 Wenatchee Valley Hospital and Clinics Wenatchee Washington United States 98801
    172 North Star Lodge Cancer Center at Yakima Valley Memorial Hospital Yakima Washington United States 98902
    173 Children's Hospital of Wisconsin Milwaukee Wisconsin United States 53226
    174 Welch Cancer Center Sheridan Wyoming United States 82801
    175 Royal Children's Hospital-Brisbane Herston Queensland Australia 4029
    176 Queensland Children's Hospital South Brisbane Queensland Australia 4101
    177 Princess Margaret Hospital for Children Perth Western Australia Australia 6008
    178 Hospital for Sick Children Toronto Ontario Canada M5G 1X8
    179 The Montreal Children's Hospital of the MUHC Montreal Quebec Canada H3H 1P3
    180 Centre Hospitalier Universitaire Sainte-Justine Montreal Quebec Canada H3T 1C5

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Jack M Su, Children's Oncology Group

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01189266
    Other Study ID Numbers:
    • NCI-2011-02600
    • NCI-2011-02600
    • ACNS0927
    • S12-02793
    • COG-ACNS0927
    • CDR0000683459
    • ACNS0927
    • ACNS0927
    • U10CA180886
    • U10CA098543
    • UM1CA097452
    First Posted:
    Aug 26, 2010
    Last Update Posted:
    Oct 28, 2021
    Last Verified:
    Oct 1, 2021
    Additional relevant MeSH terms:
    Glioma
    Astrocytoma
    Gliosarcoma
    Diffuse Intrinsic Pontine Glioma
    Vorinostat

    Study Results

    Participant Flow

    Recruitment Details Phase I /II study. Phase I determined Maximum Tolerated Dose between the first 2 treatment arms; zero patients completed therapy. Study was closed, then reopened to accrual. Phase II enrolled an additional 67 patients. Overall, 79 patients were enrolled but only 2 patients completed all 12 cycles of maintenance chemotherapy.
    Pre-assignment Detail
    Arm/Group Title Arm 1, Phase I Vorinostat 180 mg/m^2 Arm 2, Phase I Vorinostat 230 mg/m^2 Arm 3, Phase II Evaluation Vorinostat 230 mg/m^2
    Arm/Group Description Patients in phase I received vorinostat at 180 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO Patients received a higher dose of vorinostat at 230 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO Patients received a higher dose of vorinostat at 230 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/ day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO
    Period Title: Overall Study
    STARTED 6 6 67
    COMPLETED 0 0 2
    NOT COMPLETED 6 6 65

    Baseline Characteristics

    Arm/Group Title Arm 1 Phase I Vorinostat 180 mg/m^2 Arm 2 Phase 1 Vorinostat 230 mg/m^2 Arm 3 Phase II Evaluation Vorinostat 230 mg/m^2 Total
    Arm/Group Description Patients in phase I received vorinostat at 180 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO Patients received a higher dose of vorinostat at 230 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO Patients received a higher dose of vorinostat at 230 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/ day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO Total of all reporting groups
    Overall Participants 6 6 67 79
    Age (Count of Participants)
    <=18 years
    6
    100%
    6
    100%
    66
    98.5%
    78
    98.7%
    Between 18 and 65 years
    0
    0%
    0
    0%
    1
    1.5%
    1
    1.3%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Age (years) [Mean (Full Range) ]
    Mean (Full Range) [years]
    6
    9
    6
    6
    Sex: Female, Male (Count of Participants)
    Female
    4
    66.7%
    4
    66.7%
    36
    53.7%
    44
    55.7%
    Male
    2
    33.3%
    2
    33.3%
    31
    46.3%
    35
    44.3%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    16.7%
    0
    0%
    15
    22.4%
    16
    20.3%
    Not Hispanic or Latino
    5
    83.3%
    5
    83.3%
    51
    76.1%
    61
    77.2%
    Unknown or Not Reported
    0
    0%
    1
    16.7%
    1
    1.5%
    2
    2.5%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    3
    4.5%
    3
    3.8%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    8
    11.9%
    8
    10.1%
    White
    6
    100%
    5
    83.3%
    47
    70.1%
    58
    73.4%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    1
    16.7%
    9
    13.4%
    10
    12.7%
    Region of Enrollment (participants) [Number]
    United States
    5
    83.3%
    5
    83.3%
    62
    92.5%
    62
    78.5%
    Australia
    0
    0%
    0
    0%
    3
    4.5%
    3
    3.8%
    Canada
    1
    16.7%
    1
    16.7%
    1
    1.5%
    3
    3.8%
    Puerto Rico
    0
    0%
    0
    0%
    1
    1.5%
    1
    1.3%

    Outcome Measures

    1. Primary Outcome
    Title Maximum Tolerated Dose (MTD) of Vorinostat
    Description The dose of vorinostat in mg/sqm/day to be administered with combination chemotherapy and radiation therapy
    Time Frame Planned 7 weeks during chemoradiotherapy

    Outcome Measure Data

    Analysis Population Description
    All patients enrolled on arm 1 and 2 who received at least 85% of the planned doses of radiation therapy and chemotherapy in the chemoradiotherapy portion of the study or who experienced DLT after after receiving at least one dose of chemoradio therapy and completing 7 weeks fo follow-up.
    Arm/Group Title All Phase 1 Study Participants
    Arm/Group Description Arm 1, Phase 1 participants received vorinostat at 180 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Arm 2, Phase 1 participants received a higher dose of vorinostat at 230 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks).
    Measure Participants 12
    Number [mg/m^2]
    230
    2. Primary Outcome
    Title Event-Free Survival
    Description Time from enrollment to disease progression, diagnosis of a second malignant neoplasm, death or last follow-up, whichever occurs first.
    Time Frame 2 years after study enrollment

    Outcome Measure Data

    Analysis Population Description
    One patient enrolled on Arm 3 was withdrawn from study prior to the start of treatment.
    Arm/Group Title Arm 1, Phase I Vorinostat 180 mg/m^2 Arm 2, Phase I Vorinostat 230 mg/m^2 Arm 3, Phase II Evaluation Vorinostat 230 mg/m^2
    Arm/Group Description Patients in phase I received vorinostat at 180 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO Patients received a higher dose of vorinostat at 230 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO Patients received a higher dose of vorinostat at 230 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/ day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO
    Measure Participants 6 6 66
    Number (95% Confidence Interval) [percent probability]
    0
    0
    3.1
    3. Primary Outcome
    Title Incidence of Toxicity During Chemoradiation Therapy
    Description Proportion of patients who experience any grade 3 or higher CTC AE Version 4 adverse experience
    Time Frame Planned 7 weeks during chemoradiotherapy

    Outcome Measure Data

    Analysis Population Description
    All patients enrolled on Arm 1 and 2 received at least one dose of chemoradiation therapy. Two patients enrolled on arm 3 did not receive protocol therapy prior to date of removal from protocol therapy.
    Arm/Group Title Arm 1, Phase I Vorinostat 180 mg/m^2 Arm 2, Phase I Vorinostat 230 mg/m^2 Arm 3, Phase II Evaluation Vorinostat 230 mg/m^2
    Arm/Group Description Patients in phase I received vorinostat at 180 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO Patients received a higher dose of vorinostat at 230 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO Patients received a higher dose of vorinostat at 230 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/ day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO
    Measure Participants 6 6 65
    Count of Participants [Participants]
    5
    83.3%
    2
    33.3%
    24
    35.8%
    4. Primary Outcome
    Title Incidence of Toxicity During Maintenance Therapy
    Description Proportion of patients who experience any grade 3 or higher CTC AE Version 4 adverse experience
    Time Frame Planned 12 months of maintenance with Vorinostat

    Outcome Measure Data

    Analysis Population Description
    All patients enrolled on arm 1 and 2 received at least one dose of maintenance therapy. Seven patients enrolled on arm 3 did not receive maintenance therapy prior to date of removal from protocol therapy.
    Arm/Group Title Arm 1, Phase I Vorinostat 180 mg/m^2 Arm 2, Phase I Vorinostat 230 mg/m^2 Arm 3, Phase II Evaluation Vorinostat 230 mg/m^2
    Arm/Group Description Patients in phase I received vorinostat at 180 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO Patients received a higher dose of vorinostat at 230 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO Patients received a higher dose of vorinostat at 230 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/ day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO
    Measure Participants 6 6 60
    Count of Participants [Participants]
    6
    100%
    4
    66.7%
    39
    58.2%
    5. Secondary Outcome
    Title Overall Survival
    Description Time from enrollment to death or last follow-up, whichever occurs first.
    Time Frame 2 years after study enrollment

    Outcome Measure Data

    Analysis Population Description
    One patient enrolled on Arm 3 was withdrawn from study prior to the start of treatment.
    Arm/Group Title Arm 1, Phase I Vorinostat 180 mg/m^2 Arm 2, Phase I Vorinostat 230 mg/m^2 Arm 3, Phase II Evaluation Vorinostat 230 mg/m^2
    Arm/Group Description Patients in phase I received vorinostat at 180 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO Patients received a higher dose of vorinostat at 230 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO Patients received a higher dose of vorinostat at 230 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/ day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO
    Measure Participants 6 6 66
    Number (95% Confidence Interval) [percent probability]
    22
    0
    3.1
    6. Secondary Outcome
    Title Change in H3 and H4 Acetylation Levels in PBMCs
    Description Degree of acetylation in peripheral blood monocytes will be divided into quartiles and coded as none, mild, moderation or marked.
    Time Frame Baseline to up to 7 weeks

    Outcome Measure Data

    Analysis Population Description
    Due to budgetary issues the planned laboratory testing was not performed and no data were collected
    Arm/Group Title Arm 1, Phase I Vorinostat 180 mg/m^2 Arm 2, Phase I Vorinostat 230 mg/m^2 Arm 3, Phase II Evaluation Vorinostat 230 mg/m^2
    Arm/Group Description Patients in phase I received vorinostat at 180 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO Patients received a higher dose of vorinostat at 230 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO Patients received a higher dose of vorinostat at 230 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/ day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO
    Measure Participants 0 0 0
    7. Secondary Outcome
    Title Change in NHEJ Activity in PBMCs
    Description Descriptive statistics will be used to summarize the biological/laboratory measures and the changes in these measures across time-points.
    Time Frame Baseline to up to 7 weeks

    Outcome Measure Data

    Analysis Population Description
    Due to budgetary issues the planned laboratory testing was not performed and no data were collected
    Arm/Group Title Arm 1, Phase I Vorinostat 180 mg/m^2 Arm 2, Phase I Vorinostat 230 mg/m^2 Arm 3, Phase II Evaluation Vorinostat 230 mg/m^2
    Arm/Group Description Patients in phase I received vorinostat at 180 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO Patients received a higher dose of vorinostat at 230 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO Patients received a higher dose of vorinostat at 230 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/ day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO
    Measure Participants 0 0 0
    8. Secondary Outcome
    Title Levels of DNA Repair Proteins in Paraffin-embedded Blocks, Measured Via Immunohistochemistry or Western Analysis
    Description For immunohistochemistry from tumor blocks, the intensity will be graded from 1 to 3; for Western analysis, a percentage of the intensity relative to the tumor with the highest level will be measured.
    Time Frame Baseline

    Outcome Measure Data

    Analysis Population Description
    Due to budgetary issues the planned laboratory testing was not performed and no data were collected
    Arm/Group Title Arm 1, Phase I Vorinostat 180 mg/m^2 Arm 2, Phase I Vorinostat 230 mg/m^2 Arm 3, Phase II Evaluation Vorinostat 230 mg/m^2
    Arm/Group Description Patients in phase I received vorinostat at 180 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO Patients received a higher dose of vorinostat at 230 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO Patients received a higher dose of vorinostat at 230 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/ day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO
    Measure Participants 0 0 0

    Adverse Events

    Time Frame Up to 2 years
    Adverse Event Reporting Description Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.
    Arm/Group Title Arm 1 Phase I Vorinostat 180 mg/m^2 Arm 2 Phase 1 Vorinostat 230 mg/m^2 Arm 3 Phase II Evaluation Vorinostat 230 mg/m^2
    Arm/Group Description Patients in phase I received vorinostat at 180 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO Patients received a higher dose of vorinostat at 230 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO Patients received a higher dose of vorinostat at 230 mg/m^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m^2/ day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy Intensity-Modulated Radiation Therapy: Undergo intensity-modulated radiation therapy Laboratory Biomarker Analysis: Correlative studies Vorinostat: Given PO
    All Cause Mortality
    Arm 1 Phase I Vorinostat 180 mg/m^2 Arm 2 Phase 1 Vorinostat 230 mg/m^2 Arm 3 Phase II Evaluation Vorinostat 230 mg/m^2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/6 (66.7%) 6/6 (100%) 62/65 (95.4%)
    Serious Adverse Events
    Arm 1 Phase I Vorinostat 180 mg/m^2 Arm 2 Phase 1 Vorinostat 230 mg/m^2 Arm 3 Phase II Evaluation Vorinostat 230 mg/m^2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/6 (100%) 5/6 (83.3%) 55/65 (84.6%)
    Blood and lymphatic system disorders
    Anemia 0/6 (0%) 0 0/6 (0%) 0 2/65 (3.1%) 2
    Blood and lymphatic system disorders - Other, specify 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Febrile neutropenia 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Gastrointestinal disorders
    Abdominal pain 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Dysphagia 0/6 (0%) 0 0/6 (0%) 0 2/65 (3.1%) 2
    Mucositis oral 0/6 (0%) 0 0/6 (0%) 0 2/65 (3.1%) 2
    Nausea 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Vomiting 0/6 (0%) 0 1/6 (16.7%) 1 1/65 (1.5%) 1
    General disorders
    Death NOS 3/6 (50%) 3 2/6 (33.3%) 2 34/65 (52.3%) 34
    Fatigue 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Infusion related reaction 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Infections and infestations
    Catheter related infection 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Infections and infestations - Other, specify 1/6 (16.7%) 1 0/6 (0%) 0 1/65 (1.5%) 1
    Lip infection 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Lung infection 1/6 (16.7%) 1 0/6 (0%) 0 1/65 (1.5%) 1
    Sinusitis 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Skin infection 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Upper respiratory infection 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Urinary tract infection 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Investigations
    Creatinine increased 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Lymphocyte count decreased 0/6 (0%) 0 0/6 (0%) 0 6/65 (9.2%) 7
    Neutrophil count decreased 0/6 (0%) 0 0/6 (0%) 0 9/65 (13.8%) 10
    Platelet count decreased 0/6 (0%) 0 0/6 (0%) 0 9/65 (13.8%) 10
    Weight loss 0/6 (0%) 0 0/6 (0%) 0 4/65 (6.2%) 4
    White blood cell decreased 0/6 (0%) 0 0/6 (0%) 0 5/65 (7.7%) 5
    Metabolism and nutrition disorders
    Anorexia 0/6 (0%) 0 0/6 (0%) 0 3/65 (4.6%) 3
    Dehydration 0/6 (0%) 0 0/6 (0%) 0 2/65 (3.1%) 2
    Glucose intolerance 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Hyperglycemia 0/6 (0%) 0 0/6 (0%) 0 3/65 (4.6%) 4
    Hyperkalemia 0/6 (0%) 0 1/6 (16.7%) 1 0/65 (0%) 0
    Hypermagnesemia 0/6 (0%) 0 1/6 (16.7%) 1 3/65 (4.6%) 3
    Hypoalbuminemia 0/6 (0%) 0 0/6 (0%) 0 2/65 (3.1%) 2
    Hypokalemia 0/6 (0%) 0 0/6 (0%) 0 2/65 (3.1%) 2
    Hyponatremia 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Musculoskeletal and connective tissue disorders
    Muscle weakness right-sided 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify 0/6 (0%) 0 1/6 (16.7%) 1 11/65 (16.9%) 11
    Nervous system disorders
    Depressed level of consciousness 0/6 (0%) 0 0/6 (0%) 0 3/65 (4.6%) 3
    Dysarthria 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Headache 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Hydrocephalus 0/6 (0%) 0 1/6 (16.7%) 1 3/65 (4.6%) 3
    Intracranial hemorrhage 0/6 (0%) 0 0/6 (0%) 0 3/65 (4.6%) 3
    Reversible posterior leukoencephalopathy syndrome 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Seizure 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Somnolence 0/6 (0%) 0 0/6 (0%) 0 2/65 (3.1%) 2
    Spasticity 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Psychiatric disorders
    Agitation 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Confusion 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Renal and urinary disorders
    Hematuria 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Urinary retention 0/6 (0%) 0 1/6 (16.7%) 1 0/65 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Aspiration 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Dyspnea 0/6 (0%) 0 0/6 (0%) 0 3/65 (4.6%) 3
    Hypoxia 0/6 (0%) 0 0/6 (0%) 0 3/65 (4.6%) 3
    Skin and subcutaneous tissue disorders
    Rash maculo-papular 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Skin and subcutaneous tissue disorders - Other, specify 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Urticaria 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Vascular disorders
    Hypertension 0/6 (0%) 0 1/6 (16.7%) 1 3/65 (4.6%) 3
    Thromboembolic event 0/6 (0%) 0 0/6 (0%) 0 2/65 (3.1%) 2
    Other (Not Including Serious) Adverse Events
    Arm 1 Phase I Vorinostat 180 mg/m^2 Arm 2 Phase 1 Vorinostat 230 mg/m^2 Arm 3 Phase II Evaluation Vorinostat 230 mg/m^2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/6 (100%) 6/6 (100%) 51/65 (78.5%)
    Blood and lymphatic system disorders
    Anemia 6/6 (100%) 10 6/6 (100%) 8 3/65 (4.6%) 3
    Cardiac disorders
    Chest pain - cardiac 0/6 (0%) 0 1/6 (16.7%) 1 0/65 (0%) 0
    Mobitz type I 0/6 (0%) 0 1/6 (16.7%) 1 0/65 (0%) 0
    Palpitations 0/6 (0%) 0 1/6 (16.7%) 1 0/65 (0%) 0
    Sinus bradycardia 2/6 (33.3%) 2 0/6 (0%) 0 1/65 (1.5%) 1
    Sinus tachycardia 0/6 (0%) 0 1/6 (16.7%) 1 0/65 (0%) 0
    Ear and labyrinth disorders
    Ear pain 2/6 (33.3%) 2 1/6 (16.7%) 1 0/65 (0%) 0
    Tinnitus 0/6 (0%) 0 2/6 (33.3%) 2 0/65 (0%) 0
    Vertigo 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Endocrine disorders
    Adrenal insufficiency 0/6 (0%) 0 1/6 (16.7%) 1 0/65 (0%) 0
    Cushingoid 2/6 (33.3%) 2 0/6 (0%) 0 0/65 (0%) 0
    Eye disorders
    Blurred vision 1/6 (16.7%) 1 1/6 (16.7%) 1 2/65 (3.1%) 2
    Conjunctivitis 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Extraocular muscle paresis 2/6 (33.3%) 2 1/6 (16.7%) 1 1/65 (1.5%) 1
    Eye disorders - Other, specify 3/6 (50%) 3 4/6 (66.7%) 5 6/65 (9.2%) 6
    Eyelid function disorder 0/6 (0%) 0 1/6 (16.7%) 1 1/65 (1.5%) 1
    Photophobia 0/6 (0%) 0 1/6 (16.7%) 1 1/65 (1.5%) 1
    Gastrointestinal disorders
    Abdominal distension 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Abdominal pain 2/6 (33.3%) 2 2/6 (33.3%) 2 1/65 (1.5%) 1
    Anal pain 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Cheilitis 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Constipation 5/6 (83.3%) 5 5/6 (83.3%) 5 2/65 (3.1%) 2
    Diarrhea 3/6 (50%) 3 2/6 (33.3%) 2 0/65 (0%) 0
    Dry mouth 1/6 (16.7%) 1 1/6 (16.7%) 1 0/65 (0%) 0
    Dyspepsia 1/6 (16.7%) 1 1/6 (16.7%) 1 0/65 (0%) 0
    Dysphagia 3/6 (50%) 3 4/6 (66.7%) 4 3/65 (4.6%) 3
    Esophageal pain 0/6 (0%) 0 2/6 (33.3%) 2 0/65 (0%) 0
    Fecal incontinence 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Flatulence 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Gastroesophageal reflux disease 0/6 (0%) 0 1/6 (16.7%) 1 0/65 (0%) 0
    Mucositis oral 3/6 (50%) 3 0/6 (0%) 0 1/65 (1.5%) 1
    Nausea 4/6 (66.7%) 4 5/6 (83.3%) 6 5/65 (7.7%) 5
    Oral hemorrhage 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Stomach pain 1/6 (16.7%) 1 1/6 (16.7%) 1 0/65 (0%) 0
    Vomiting 5/6 (83.3%) 8 5/6 (83.3%) 7 6/65 (9.2%) 6
    General disorders
    Chills 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Fatigue 5/6 (83.3%) 5 6/6 (100%) 8 9/65 (13.8%) 10
    Fever 3/6 (50%) 3 0/6 (0%) 0 2/65 (3.1%) 2
    Flu like symptoms 0/6 (0%) 0 1/6 (16.7%) 1 0/65 (0%) 0
    Gait disturbance 1/6 (16.7%) 1 3/6 (50%) 3 5/65 (7.7%) 5
    General disorders and administration site conditions - Other, specify 0/6 (0%) 0 0/6 (0%) 0 2/65 (3.1%) 2
    Irritability 2/6 (33.3%) 4 1/6 (16.7%) 1 3/65 (4.6%) 3
    Malaise 0/6 (0%) 0 1/6 (16.7%) 1 2/65 (3.1%) 2
    Pain 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Immune system disorders
    Allergic reaction 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Infections and infestations
    Bladder infection 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Bronchial infection 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Conjunctivitis infective 0/6 (0%) 0 1/6 (16.7%) 1 0/65 (0%) 0
    Infections and infestations - Other, specify 2/6 (33.3%) 2 1/6 (16.7%) 1 2/65 (3.1%) 2
    Lip infection 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Mucosal infection 1/6 (16.7%) 1 2/6 (33.3%) 3 2/65 (3.1%) 2
    Otitis media 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Sinusitis 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Skin infection 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Upper respiratory infection 0/6 (0%) 0 1/6 (16.7%) 1 0/65 (0%) 0
    Wound infection 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Injury, poisoning and procedural complications
    Bruising 1/6 (16.7%) 1 1/6 (16.7%) 1 0/65 (0%) 0
    Dermatitis radiation 2/6 (33.3%) 2 0/6 (0%) 0 0/65 (0%) 0
    Injury, poisoning and procedural complications - Other, specify 0/6 (0%) 0 1/6 (16.7%) 1 0/65 (0%) 0
    Investigations
    Alanine aminotransferase increased 6/6 (100%) 7 4/6 (66.7%) 4 3/65 (4.6%) 3
    Alkaline phosphatase increased 2/6 (33.3%) 2 0/6 (0%) 0 1/65 (1.5%) 1
    Aspartate aminotransferase increased 3/6 (50%) 3 1/6 (16.7%) 1 1/65 (1.5%) 1
    Blood bilirubin increased 3/6 (50%) 5 2/6 (33.3%) 2 0/65 (0%) 0
    Cholesterol high 1/6 (16.7%) 1 1/6 (16.7%) 1 2/65 (3.1%) 2
    Creatinine increased 5/6 (83.3%) 5 2/6 (33.3%) 2 3/65 (4.6%) 3
    GGT increased 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Investigations - Other, specify 0/6 (0%) 0 1/6 (16.7%) 1 0/65 (0%) 0
    Lipase increased 0/6 (0%) 0 1/6 (16.7%) 1 0/65 (0%) 0
    Lymphocyte count decreased 6/6 (100%) 15 5/6 (83.3%) 9 9/65 (13.8%) 9
    Lymphocyte count increased 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Neutrophil count decreased 5/6 (83.3%) 8 4/6 (66.7%) 6 8/65 (12.3%) 9
    Platelet count decreased 5/6 (83.3%) 10 5/6 (83.3%) 6 7/65 (10.8%) 7
    Serum amylase increased 1/6 (16.7%) 2 0/6 (0%) 0 0/65 (0%) 0
    Weight gain 2/6 (33.3%) 2 0/6 (0%) 0 1/65 (1.5%) 1
    Weight loss 0/6 (0%) 0 2/6 (33.3%) 2 2/65 (3.1%) 2
    White blood cell decreased 6/6 (100%) 12 4/6 (66.7%) 7 8/65 (12.3%) 9
    Metabolism and nutrition disorders
    Anorexia 4/6 (66.7%) 4 4/6 (66.7%) 5 2/65 (3.1%) 2
    Dehydration 0/6 (0%) 0 0/6 (0%) 0 2/65 (3.1%) 2
    Hypercalcemia 1/6 (16.7%) 1 1/6 (16.7%) 1 0/65 (0%) 0
    Hyperglycemia 4/6 (66.7%) 5 4/6 (66.7%) 6 6/65 (9.2%) 6
    Hyperkalemia 0/6 (0%) 0 1/6 (16.7%) 1 1/65 (1.5%) 1
    Hypermagnesemia 4/6 (66.7%) 4 6/6 (100%) 6 3/65 (4.6%) 3
    Hypernatremia 1/6 (16.7%) 1 1/6 (16.7%) 1 0/65 (0%) 0
    Hypertriglyceridemia 1/6 (16.7%) 2 0/6 (0%) 0 0/65 (0%) 0
    Hypoalbuminemia 3/6 (50%) 4 1/6 (16.7%) 1 0/65 (0%) 0
    Hypocalcemia 2/6 (33.3%) 2 2/6 (33.3%) 2 2/65 (3.1%) 2
    Hypoglycemia 2/6 (33.3%) 3 0/6 (0%) 0 1/65 (1.5%) 1
    Hypokalemia 5/6 (83.3%) 5 1/6 (16.7%) 1 4/65 (6.2%) 4
    Hyponatremia 2/6 (33.3%) 2 3/6 (50%) 3 4/65 (6.2%) 4
    Hypophosphatemia 3/6 (50%) 3 2/6 (33.3%) 2 1/65 (1.5%) 1
    Metabolism and nutrition disorders - Other, specify 1/6 (16.7%) 2 2/6 (33.3%) 2 0/65 (0%) 0
    Musculoskeletal and connective tissue disorders
    Back pain 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Generalized muscle weakness 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Muscle weakness left-sided 3/6 (50%) 5 0/6 (0%) 0 1/65 (1.5%) 1
    Muscle weakness lower limb 1/6 (16.7%) 1 1/6 (16.7%) 1 0/65 (0%) 0
    Muscle weakness right-sided 2/6 (33.3%) 2 2/6 (33.3%) 2 6/65 (9.2%) 6
    Muscle weakness upper limb 0/6 (0%) 0 1/6 (16.7%) 1 2/65 (3.1%) 2
    Pain in extremity 0/6 (0%) 0 2/6 (33.3%) 2 0/65 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify 1/6 (16.7%) 1 3/6 (50%) 3 13/65 (20%) 13
    Nervous system disorders
    Abducens nerve disorder 2/6 (33.3%) 2 2/6 (33.3%) 2 12/65 (18.5%) 12
    Accessory nerve disorder 0/6 (0%) 0 1/6 (16.7%) 1 0/65 (0%) 0
    Amnesia 0/6 (0%) 0 1/6 (16.7%) 1 0/65 (0%) 0
    Ataxia 6/6 (100%) 6 6/6 (100%) 6 19/65 (29.2%) 19
    Concentration impairment 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Dizziness 2/6 (33.3%) 2 0/6 (0%) 0 3/65 (4.6%) 3
    Dysarthria 5/6 (83.3%) 6 1/6 (16.7%) 1 12/65 (18.5%) 13
    Dysgeusia 1/6 (16.7%) 1 1/6 (16.7%) 1 0/65 (0%) 0
    Dysphasia 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Extrapyramidal disorder 0/6 (0%) 0 1/6 (16.7%) 1 0/65 (0%) 0
    Facial muscle weakness 0/6 (0%) 0 0/6 (0%) 0 5/65 (7.7%) 5
    Facial nerve disorder 3/6 (50%) 3 3/6 (50%) 3 12/65 (18.5%) 12
    Glossopharyngeal nerve disorder 1/6 (16.7%) 2 0/6 (0%) 0 3/65 (4.6%) 3
    Headache 4/6 (66.7%) 4 5/6 (83.3%) 6 9/65 (13.8%) 9
    Hydrocephalus 1/6 (16.7%) 1 0/6 (0%) 0 5/65 (7.7%) 6
    Hypoglossal nerve disorder 2/6 (33.3%) 2 0/6 (0%) 0 2/65 (3.1%) 2
    Intracranial hemorrhage 0/6 (0%) 0 1/6 (16.7%) 1 0/65 (0%) 0
    Lethargy 0/6 (0%) 0 1/6 (16.7%) 1 0/65 (0%) 0
    Nervous system disorders - Other, specify 1/6 (16.7%) 1 1/6 (16.7%) 2 5/65 (7.7%) 5
    Nystagmus 1/6 (16.7%) 1 2/6 (33.3%) 2 3/65 (4.6%) 3
    Paresthesia 1/6 (16.7%) 1 2/6 (33.3%) 2 0/65 (0%) 0
    Peripheral motor neuropathy 1/6 (16.7%) 1 1/6 (16.7%) 1 1/65 (1.5%) 1
    Peripheral sensory neuropathy 2/6 (33.3%) 2 0/6 (0%) 0 0/65 (0%) 0
    Pyramidal tract syndrome 0/6 (0%) 0 0/6 (0%) 0 2/65 (3.1%) 2
    Seizure 0/6 (0%) 0 0/6 (0%) 0 2/65 (3.1%) 2
    Spasticity 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Tremor 1/6 (16.7%) 1 1/6 (16.7%) 1 0/65 (0%) 0
    Trigeminal nerve disorder 0/6 (0%) 0 1/6 (16.7%) 1 0/65 (0%) 0
    Vagus nerve disorder 1/6 (16.7%) 1 1/6 (16.7%) 2 1/65 (1.5%) 1
    Psychiatric disorders
    Agitation 1/6 (16.7%) 1 1/6 (16.7%) 1 2/65 (3.1%) 3
    Anxiety 1/6 (16.7%) 1 1/6 (16.7%) 1 1/65 (1.5%) 1
    Confusion 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Depression 1/6 (16.7%) 1 2/6 (33.3%) 2 0/65 (0%) 0
    Insomnia 1/6 (16.7%) 1 2/6 (33.3%) 3 1/65 (1.5%) 1
    Personality change 0/6 (0%) 0 1/6 (16.7%) 1 1/65 (1.5%) 1
    Psychiatric disorders - Other, specify 0/6 (0%) 0 1/6 (16.7%) 1 0/65 (0%) 0
    Renal and urinary disorders
    Bladder spasm 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Hematuria 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Renal and urinary disorders - Other, specify 2/6 (33.3%) 2 1/6 (16.7%) 1 0/65 (0%) 0
    Urinary incontinence 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Urinary retention 1/6 (16.7%) 1 2/6 (33.3%) 2 1/65 (1.5%) 1
    Urinary tract pain 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Apnea 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Cough 4/6 (66.7%) 4 1/6 (16.7%) 1 0/65 (0%) 0
    Dyspnea 2/6 (33.3%) 2 1/6 (16.7%) 1 0/65 (0%) 0
    Epistaxis 2/6 (33.3%) 2 2/6 (33.3%) 2 0/65 (0%) 0
    Hiccups 0/6 (0%) 0 1/6 (16.7%) 1 0/65 (0%) 0
    Hypoxia 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Nasal congestion 2/6 (33.3%) 2 1/6 (16.7%) 1 0/65 (0%) 0
    Respiratory, thoracic and mediastinal disorders - Other, specify 0/6 (0%) 0 1/6 (16.7%) 1 1/65 (1.5%) 1
    Sneezing 0/6 (0%) 0 1/6 (16.7%) 1 0/65 (0%) 0
    Sore throat 2/6 (33.3%) 2 1/6 (16.7%) 1 0/65 (0%) 0
    Skin and subcutaneous tissue disorders
    Alopecia 2/6 (33.3%) 2 3/6 (50%) 3 0/65 (0%) 0
    Hyperhidrosis 0/6 (0%) 0 1/6 (16.7%) 1 0/65 (0%) 0
    Pruritus 2/6 (33.3%) 2 0/6 (0%) 0 0/65 (0%) 0
    Rash acneiform 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Rash maculo-papular 3/6 (50%) 3 2/6 (33.3%) 2 1/65 (1.5%) 1
    Skin and subcutaneous tissue disorders - Other, specify 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Skin hyperpigmentation 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Skin hypopigmentation 0/6 (0%) 0 1/6 (16.7%) 1 0/65 (0%) 0
    Surgical and medical procedures
    Surgical and medical procedures - Other, specify 0/6 (0%) 0 0/6 (0%) 0 1/65 (1.5%) 1
    Vascular disorders
    Hematoma 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Hot flashes 1/6 (16.7%) 1 0/6 (0%) 0 0/65 (0%) 0
    Hypertension 5/6 (83.3%) 7 2/6 (33.3%) 3 2/65 (3.1%) 2
    Hypotension 1/6 (16.7%) 1 0/6 (0%) 0 1/65 (1.5%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Results Reporting Coordinator
    Organization Children's Oncology Group
    Phone 626-447-0064
    Email resultsreportingcoordinator@childrensoncologygroup.org
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01189266
    Other Study ID Numbers:
    • NCI-2011-02600
    • NCI-2011-02600
    • ACNS0927
    • S12-02793
    • COG-ACNS0927
    • CDR0000683459
    • ACNS0927
    • ACNS0927
    • U10CA180886
    • U10CA098543
    • UM1CA097452
    First Posted:
    Aug 26, 2010
    Last Update Posted:
    Oct 28, 2021
    Last Verified:
    Oct 1, 2021