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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01189266
Other study ID # NCI-2011-02600
Secondary ID NCI-2011-02600AC
Status Completed
Phase Phase 1/Phase 2
First received
Last updated
Start date August 9, 2010
Est. completion date September 30, 2021

Study information

Verified date October 2021
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

PRIMARY OBJECTIVES: l. 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). II. To define and describe the toxicities of vorinostat given concurrently with radiation in children with newly diagnosed DIPG. III. 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). IV. To determine the toxicities of vorinostat for 12 additional courses after completion of vorinostat and radiation. SECONDARY OBJECTIVES: I. 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. II. 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. III. 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.


Recruitment information / eligibility

Status Completed
Enrollment 79
Est. completion date September 30, 2021
Est. primary completion date June 30, 2017
Accepts healthy volunteers No
Gender All
Age group 37 Months to 21 Years
Eligibility 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

Study Design


Intervention

Radiation:
3-Dimensional Conformal Radiation Therapy
Undergo 3D conformal radiation therapy
Intensity-Modulated Radiation Therapy
Undergo intensity-modulated radiation therapy
Other:
Laboratory Biomarker Analysis
Correlative studies
Drug:
Vorinostat
Given PO

Locations

Country Name City State
Australia Royal Children's Hospital-Brisbane Herston Queensland
Australia Princess Margaret Hospital for Children Perth Western Australia
Australia Queensland Children's Hospital South Brisbane Queensland
Canada Centre Hospitalier Universitaire Sainte-Justine Montreal Quebec
Canada The Montreal Children's Hospital of the MUHC Montreal Quebec
Canada Hospital for Sick Children Toronto Ontario
United States Children's Hospital Medical Center of Akron Akron Ohio
United States Cleveland Clinic Akron General Akron Ohio
United States University of New Mexico Cancer Center Albuquerque New Mexico
United States Saint Anthony's Health Alton Illinois
United States Cancer Care Center at Island Hospital Anacortes Washington
United States AnMed Health Hospital Anderson South Carolina
United States C S Mott Children's Hospital Ann Arbor Michigan
United States Michigan Cancer Research Consortium NCORP Ann Arbor Michigan
United States Saint Joseph Mercy Hospital Ann Arbor Michigan
United States Kaiser Permanente-Deer Valley Medical Center Antioch California
United States Mission Hospital Asheville North Carolina
United States Children's Healthcare of Atlanta - Egleston Atlanta Georgia
United States Children's Hospital Colorado Aurora Colorado
United States PeaceHealth Saint Joseph Medical Center Bellingham Washington
United States Saint Charles Health System Bend Oregon
United States Billings Clinic Cancer Center Billings Montana
United States Montana Cancer Consortium NCORP Billings Montana
United States Saint Vincent Frontier Cancer Center Billings Montana
United States Saint Vincent Healthcare Billings Montana
United States Children's Hospital of Alabama Birmingham Alabama
United States University of Alabama at Birmingham Cancer Center Birmingham Alabama
United States Saint Alphonsus Cancer Care Center-Boise Boise Idaho
United States Dana-Farber Cancer Institute Boston Massachusetts
United States Bozeman Deaconess Hospital Bozeman Montana
United States Harrison HealthPartners Hematology and Oncology-Bremerton Bremerton Washington
United States Montefiore Medical Center - Moses Campus Bronx New York
United States Roswell Park Cancer Institute Buffalo New York
United States Highline Medical Center-Main Campus Burien Washington
United States Saint Francis Medical Center Cape Girardeau Missouri
United States Carolinas Medical Center/Levine Cancer Institute Charlotte North Carolina
United States Lurie Children's Hospital-Chicago Chicago Illinois
United States Cincinnati Children's Hospital Medical Center Cincinnati Ohio
United States Prisma Health Richland Hospital Columbia South Carolina
United States Nationwide Children's Hospital Columbus Ohio
United States Driscoll Children's Hospital Corpus Christi Texas
United States Beaumont Hospital - Dearborn Dearborn Michigan
United States Decatur Memorial Hospital Decatur Illinois
United States Blank Children's Hospital Des Moines Iowa
United States Ascension Saint John Hospital Detroit Michigan
United States Kaiser Permanente Downey Medical Center Downey California
United States Genesys Regional Medical Center-West Flint Campus Flint Michigan
United States Hurley Medical Center Flint Michigan
United States Golisano Children's Hospital of Southwest Florida Fort Myers Florida
United States Lee Memorial Health System Fort Myers Florida
United States Kaiser Permanente-Fremont Fremont California
United States Kaiser Permanente-Fresno Fresno California
United States Wayne Memorial Hospital Goldsboro North Carolina
United States Helen DeVos Children's Hospital at Spectrum Health Grand Rapids Michigan
United States Benefis Healthcare- Sletten Cancer Institute Great Falls Montana
United States Great Falls Clinic Great Falls Montana
United States BI-LO Charities Children's Cancer Center Greenville South Carolina
United States Greenville Cancer Treatment Center Greenville South Carolina
United States Saint Francis Hospital Greenville South Carolina
United States Smilow Cancer Hospital Care Center at Saint Francis Hartford Connecticut
United States Saint Peter's Community Hospital Helena Montana
United States Margaret R Pardee Memorial Hospital Hendersonville North Carolina
United States Penn State Children's Hospital Hershey Pennsylvania
United States Kaiser Permanente Moanalua Medical Center Honolulu Hawaii
United States University of Hawaii Cancer Center Honolulu Hawaii
United States Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center Houston Texas
United States Riley Hospital for Children Indianapolis Indiana
United States Allegiance Health Jackson Michigan
United States University of Mississippi Medical Center Jackson Mississippi
United States Nemours Children's Clinic-Jacksonville Jacksonville Florida
United States Glacier Oncology PLLC Kalispell Montana
United States Kalispell Regional Medical Center Kalispell Montana
United States Children's Mercy Hospitals and Clinics Kansas City Missouri
United States CHI Health Good Samaritan Kearney Nebraska
United States Kadlec Clinic Hematology and Oncology Kennewick Washington
United States Carolina Blood and Cancer Care Associates PA-Lancaster Lancaster South Carolina
United States Sparrow Hospital Lansing Michigan
United States Baptist Health Lexington Lexington Kentucky
United States University of Kentucky/Markey Cancer Center Lexington Kentucky
United States Arkansas Children's Hospital Little Rock Arkansas
United States University of Arkansas for Medical Sciences Little Rock Arkansas
United States Saint Mary Mercy Hospital Livonia Michigan
United States Miller Children's and Women's Hospital Long Beach Long Beach California
United States Cedars Sinai Medical Center Los Angeles California
United States Norton Children's Hospital Louisville Kentucky
United States Valley Children's Hospital Madera California
United States Contra Costa Regional Medical Center Martinez California
United States Loyola University Medical Center Maywood Illinois
United States Saint Jude Children's Research Hospital Memphis Tennessee
United States Children's Hospital of Wisconsin Milwaukee Wisconsin
United States University of Minnesota/Masonic Cancer Center Minneapolis Minnesota
United States Saint Patrick Hospital - Community Hospital Missoula Montana
United States Providence Hospital Mobile Alabama
United States Morristown Medical Center Morristown New Jersey
United States Good Samaritan Regional Health Center Mount Vernon Illinois
United States Skagit Valley Hospital Mount Vernon Washington
United States El Camino Hospital Mountain View California
United States Edward Hospital/Cancer Center Naperville Illinois
United States Vanderbilt University/Ingram Cancer Center Nashville Tennessee
United States Saint Peter's University Hospital New Brunswick New Jersey
United States Laura and Isaac Perlmutter Cancer Center at NYU Langone New York New York
United States NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center New York New York
United States Newark Beth Israel Medical Center Newark New Jersey
United States Children's Hospital of The King's Daughters Norfolk Virginia
United States Alta Bates Summit Medical Center - Summit Campus Oakland California
United States Bay Area Tumor Institute Oakland California
United States Highland General Hospital Oakland California
United States Kaiser Permanente-Oakland Oakland California
United States UCSF Benioff Children's Hospital Oakland Oakland California
United States Children's Hospital of Orange County Orange California
United States AdventHealth Orlando Orlando Florida
United States Arnold Palmer Hospital for Children Orlando Florida
United States Nemours Children's Clinic - Orlando Orlando Florida
United States Nemours Children's Hospital Orlando Florida
United States Orlando Health Cancer Institute Orlando Florida
United States Singing River Hospital Pascagoula Mississippi
United States Nemours Children's Clinic - Pensacola Pensacola Florida
United States Saint Jude Midwest Affiliate Peoria Illinois
United States Children's Hospital of Philadelphia Philadelphia Pennsylvania
United States Saint Joseph Mercy Oakland Pontiac Michigan
United States Lake Huron Medical Center Port Huron Michigan
United States Legacy Emanuel Children's Hospital Portland Oregon
United States Oregon Health and Science University Portland Oregon
United States Harrison HealthPartners Hematology and Oncology-Poulsbo Poulsbo Washington
United States Kaiser Permanente-Redwood City Redwood City California
United States Kaiser Permanente-Richmond Richmond California
United States Highlands Oncology Group Rogers Arkansas
United States Kaiser Permanente-Roseville Roseville California
United States Kaiser Permanente - Sacramento Sacramento California
United States Kaiser Permanente-South Sacramento Sacramento California
United States Ascension Saint Mary's Hospital Saginaw Michigan
United States Cardinal Glennon Children's Medical Center Saint Louis Missouri
United States Saint Louis Cancer and Breast Institute-South City Saint Louis Missouri
United States Saint Louis-Cape Girardeau CCOP Saint Louis Missouri
United States Washington University School of Medicine Saint Louis Missouri
United States Johns Hopkins All Children's Hospital Saint Petersburg Florida
United States Primary Children's Hospital Salt Lake City Utah
United States Methodist Children's Hospital of South Texas San Antonio Texas
United States Rady Children's Hospital - San Diego San Diego California
United States Kaiser Permanente-San Francisco San Francisco California
United States UCSF Medical Center-Mission Bay San Francisco California
United States UCSF Medical Center-Parnassus San Francisco California
United States Kaiser Permanente-Santa Teresa-San Jose San Jose California
United States Kaiser Permanente San Leandro San Leandro California
United States Doctors Medical Center- JC Robinson Regional Cancer Center San Pablo California
United States Kaiser Permanente-San Rafael San Rafael California
United States Kaiser Permanente Medical Center - Santa Clara Santa Clara California
United States Kaiser Permanente-Santa Rosa Santa Rosa California
United States Memorial Health University Medical Center Savannah Georgia
United States Fred Hutchinson Cancer Research Center Seattle Washington
United States Harborview Medical Center Seattle Washington
United States Kaiser Permanente Washington Seattle Washington
United States Minor and James Medical PLLC Seattle Washington
United States Seattle Children's Hospital Seattle Washington
United States Swedish Medical Center-First Hill Seattle Washington
United States University of Washington Medical Center - Montlake Seattle Washington
United States PeaceHealth United General Medical Center Sedro-Woolley Washington
United States Welch Cancer Center Sheridan Wyoming
United States Kaiser Permanente-South San Francisco South San Francisco California
United States Spartanburg Medical Center Spartanburg South Carolina
United States Cancer Care Northwest - Spokane South Spokane Washington
United States Evergreen Hematology and Oncology PS Spokane Washington
United States Cancer Research for the Ozarks NCORP Springfield Missouri
United States CoxHealth South Hospital Springfield Missouri
United States Memorial Medical Center Springfield Illinois
United States Mercy Hospital Springfield Springfield Missouri
United States Iredell Memorial Hospital Statesville North Carolina
United States Kaiser Permanente-Stockton Stockton California
United States Overlook Hospital Summit New Jersey
United States Mary Bridge Children's Hospital and Health Center Tacoma Washington
United States Kaiser Permanente Medical Center-Vacaville Vacaville California
United States Kaiser Permanente-Vallejo Vallejo California
United States Kaiser Permanente-Walnut Creek Walnut Creek California
United States Saint John Macomb-Oakland Hospital Warren Michigan
United States Children's National Medical Center Washington District of Columbia
United States Wenatchee Valley Hospital and Clinics Wenatchee Washington
United States Alfred I duPont Hospital for Children Wilmington Delaware
United States Southeast Clinical Oncology Research Consortium NCORP Winston-Salem North Carolina
United States Wake Forest University Health Sciences Winston-Salem North Carolina
United States North Star Lodge Cancer Center at Yakima Valley Memorial Hospital Yakima Washington

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary Maximum Tolerated Dose (MTD) of Vorinostat The dose of vorinostat in mg/sqm/day to be administered with combination chemotherapy and radiation therapy Planned 7 weeks during chemoradiotherapy
Primary Event-Free Survival Time from enrollment to disease progression, diagnosis of a second malignant neoplasm, death or last follow-up, whichever occurs first. 2 years after study enrollment
Primary Incidence of Toxicity During Chemoradiation Therapy Proportion of patients who experience any grade 3 or higher CTC AE Version 4 adverse experience Planned 7 weeks during chemoradiotherapy
Primary Incidence of Toxicity During Maintenance Therapy Proportion of patients who experience any grade 3 or higher CTC AE Version 4 adverse experience Planned 12 months of maintenance with Vorinostat
Secondary Overall Survival Time from enrollment to death or last follow-up, whichever occurs first. 2 years after study enrollment
Secondary Change in H3 and H4 Acetylation Levels in PBMCs Degree of acetylation in peripheral blood monocytes will be divided into quartiles and coded as none, mild, moderation or marked. Baseline to up to 7 weeks
Secondary Change in NHEJ Activity in PBMCs Descriptive statistics will be used to summarize the biological/laboratory measures and the changes in these measures across time-points. Baseline to up to 7 weeks
Secondary Levels of DNA Repair Proteins in Paraffin-embedded Blocks, Measured Via Immunohistochemistry or Western Analysis 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. Baseline
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