Anaplastic AstrocytomaPhase 1/2NCT01189266
Vorinostat and Radiation Therapy Followed by Maintenance Therapy With Vorinostat in Treating Younger Patients With Newly Diagnosed Diffuse Intrinsic Pontine Glioma
A Phase 1/2 study testing 3-Dimensional Conformal Radiation Therapy, Intensity-Modulated Radiation Therapy and Laboratory Biomarker Analysis in people with Anaplastic Astrocytoma and Anaplastic Oligoastrocytoma, run by National Cancer Institute (NCI) at 180 sites in 3 countries.
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). Read more about this study
- Who is it for?
- Ages 37 months to 21 years
- Conditions the study is for
- Anaplastic Astrocytoma, Anaplastic Oligoastrocytoma, Diffuse Intrinsic Pontine Glioma
- What is being tested?
- 3-Dimensional Conformal Radiation Therapy, Intensity-Modulated Radiation Therapy and Laboratory Biomarker Analysis
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 79 participants
- Where
- 180 sitesin 3 countries
- Study dates
- 9 Aug 2010to 30 Sep 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 37 months to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
180 sites in 3 countries.
180 sites in 3 countries
United States174 sites
Cleveland Clinic Akron General
Akron, Ohio, 44307
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87102
Saint Anthony's Health
Alton, Illinois, 62002
Cancer Care Center at Island Hospital
Anacortes, Washington, 98221
AnMed Health Hospital
Anderson, South Carolina, 29621
Michigan Cancer Research Consortium NCORP
Ann Arbor, Michigan, 48106
Saint Joseph Mercy Hospital
Ann Arbor, Michigan, 48106
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109
Kaiser Permanente-Deer Valley Medical Center
Antioch, California, 94531
Mission Hospital
Asheville, North Carolina, 28801
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322
Children's Hospital Colorado
Aurora, Colorado, 80045
PeaceHealth Saint Joseph Medical Center
Bellingham, Washington, 98225
Saint Charles Health System
Bend, Oregon, 97701
Billings Clinic Cancer Center
Billings, Montana, 59101
Saint Vincent Healthcare
Billings, Montana, 59101
Montana Cancer Consortium NCORP
Billings, Montana, 59102
Saint Vincent Frontier Cancer Center
Billings, Montana, 59102
Children's Hospital of Alabama
Birmingham, Alabama, 35233
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Bozeman Deaconess Hospital
Bozeman, Montana, 59715
Harrison HealthPartners Hematology and Oncology-Bremerton
Bremerton, Washington, 98310
Roswell Park Cancer Institute
Buffalo, New York, 14263
Highline Medical Center-Main Campus
Burien, Washington, 98166
Saint Francis Medical Center
Cape Girardeau, Missouri, 63703
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Prisma Health Richland Hospital
Columbia, South Carolina, 29203
Nationwide Children's Hospital
Columbus, Ohio, 43205
Driscoll Children's Hospital
Corpus Christi, Texas, 78411
Beaumont Hospital - Dearborn
Dearborn, Michigan, 48124
Decatur Memorial Hospital
Decatur, Illinois, 62526
Blank Children's Hospital
Des Moines, Iowa, 50309
Ascension Saint John Hospital
Detroit, Michigan, 48236
Kaiser Permanente Downey Medical Center
Downey, California, 90242
Hurley Medical Center
Flint, Michigan, 48503
Genesys Regional Medical Center-West Flint Campus
Flint, Michigan, 48532
Lee Memorial Health System
Fort Myers, Florida, 33901
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908
Kaiser Permanente-Fremont
Fremont, California, 94538
Kaiser Permanente-Fresno
Fresno, California, 93720
Wayne Memorial Hospital
Goldsboro, North Carolina, 27534
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids, Michigan, 49503
Benefis Healthcare- Sletten Cancer Institute
Great Falls, Montana, 59405
Great Falls Clinic
Great Falls, Montana, 59405
Saint Francis Hospital
Greenville, South Carolina, 29601
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605
Greenville Cancer Treatment Center
Greenville, South Carolina, 29605
Smilow Cancer Hospital Care Center at Saint Francis
Hartford, Connecticut, 06105
Saint Peter's Community Hospital
Helena, Montana, 59601
Margaret R Pardee Memorial Hospital
Hendersonville, North Carolina, 28791
Penn State Children's Hospital
Hershey, Pennsylvania, 17033
University of Hawaii Cancer Center
Honolulu, Hawaii, 96813
Kaiser Permanente Moanalua Medical Center
Honolulu, Hawaii, 96819
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
Riley Hospital for Children
Indianapolis, Indiana, 46202
Allegiance Health
Jackson, Michigan, 49201
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207
Glacier Oncology PLLC
Kalispell, Montana, 59901
Kalispell Regional Medical Center
Kalispell, Montana, 59901
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
CHI Health Good Samaritan
Kearney, Nebraska, 68847
Kadlec Clinic Hematology and Oncology
Kennewick, Washington, 99336
Carolina Blood and Cancer Care Associates PA-Lancaster
Lancaster, South Carolina, 29720
Sparrow Hospital
Lansing, Michigan, 48912
Baptist Health Lexington
Lexington, Kentucky, 40503
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Saint Mary Mercy Hospital
Livonia, Michigan, 48154
Miller Children's and Women's Hospital Long Beach
Long Beach, California, 90806
Cedars Sinai Medical Center
Los Angeles, California, 90048
Norton Children's Hospital
Louisville, Kentucky, 40202
Valley Children's Hospital
Madera, California, 93636
Contra Costa Regional Medical Center
Martinez, California, 94553-3156
Loyola University Medical Center
Maywood, Illinois, 60153
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455
Saint Patrick Hospital - Community Hospital
Missoula, Montana, 59802
Providence Hospital
Mobile, Alabama, 36608
Morristown Medical Center
Morristown, New Jersey, 07960
Good Samaritan Regional Health Center
Mount Vernon, Illinois, 62864
Skagit Valley Hospital
Mount Vernon, Washington, 98274
El Camino Hospital
Mountain View, California, 94040
Edward Hospital/Cancer Center
Naperville, Illinois, 60540
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Saint Peter's University Hospital
New Brunswick, New Jersey, 08901
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Newark Beth Israel Medical Center
Newark, New Jersey, 07112
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507
Highland General Hospital
Oakland, California, 94602
Alta Bates Summit Medical Center - Summit Campus
Oakland, California, 94609
Bay Area Tumor Institute
Oakland, California, 94609
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609
Kaiser Permanente-Oakland
Oakland, California, 94611
Children's Hospital of Orange County
Orange, California, 92868
AdventHealth Orlando
Orlando, Florida, 32803
Arnold Palmer Hospital for Children
Orlando, Florida, 32806
Nemours Children's Clinic - Orlando
Orlando, Florida, 32806
Orlando Health Cancer Institute
Orlando, Florida, 32806
Nemours Children's Hospital
Orlando, Florida, 32827
Singing River Hospital
Pascagoula, Mississippi, 39581
Nemours Children's Clinic - Pensacola
Pensacola, Florida, 32504
Saint Jude Midwest Affiliate
Peoria, Illinois, 61637
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Saint Joseph Mercy Oakland
Pontiac, Michigan, 48341
Lake Huron Medical Center
Port Huron, Michigan, 48060
Legacy Emanuel Children's Hospital
Portland, Oregon, 97227
Oregon Health and Science University
Portland, Oregon, 97239
Harrison HealthPartners Hematology and Oncology-Poulsbo
Poulsbo, Washington, 98370
Kaiser Permanente-Redwood City
Redwood City, California, 94063
Kaiser Permanente-Richmond
Richmond, California, 94801
Highlands Oncology Group
Rogers, Arkansas, 72758
Kaiser Permanente-Roseville
Roseville, California, 95661
Kaiser Permanente-South Sacramento
Sacramento, California, 95823
Kaiser Permanente - Sacramento
Sacramento, California, 95825
Ascension Saint Mary's Hospital
Saginaw, Michigan, 48601
Primary Children's Hospital
Salt Lake City, Utah, 84113
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229
Rady Children's Hospital - San Diego
San Diego, California, 92123
Kaiser Permanente-San Francisco
San Francisco, California, 94115
UCSF Medical Center-Parnassus
San Francisco, California, 94143
UCSF Medical Center-Mission Bay
San Francisco, California, 94158
Kaiser Permanente-Santa Teresa-San Jose
San Jose, California, 95119
Kaiser Permanente San Leandro
San Leandro, California, 94577
Doctors Medical Center- JC Robinson Regional Cancer Center
San Pablo, California, 94806
Kaiser Permanente-San Rafael
San Rafael, California, 94903
Kaiser Permanente Medical Center - Santa Clara
Santa Clara, California, 95051
Kaiser Permanente-Santa Rosa
Santa Rosa, California, 95403
Memorial Health University Medical Center
Savannah, Georgia, 31404
Harborview Medical Center
Seattle, Washington, 98104
Minor and James Medical PLLC
Seattle, Washington, 98104
Seattle Children's Hospital
Seattle, Washington, 98105
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
Kaiser Permanente Washington
Seattle, Washington, 98112
Swedish Medical Center-First Hill
Seattle, Washington, 98122-4307
University of Washington Medical Center - Montlake
Seattle, Washington, 98195
PeaceHealth United General Medical Center
Sedro-Woolley, Washington, 98284
Welch Cancer Center
Sheridan, Wyoming, 82801
Kaiser Permanente-South San Francisco
South San Francisco, California, 94080
Spartanburg Medical Center
Spartanburg, South Carolina, 29303
Cancer Care Northwest - Spokane South
Spokane, Washington, 99202
Evergreen Hematology and Oncology PS
Spokane, Washington, 99218
Memorial Medical Center
Springfield, Illinois, 62781
Cancer Research for the Ozarks NCORP
Springfield, Missouri, 65804
Mercy Hospital Springfield
Springfield, Missouri, 65804
CoxHealth South Hospital
Springfield, Missouri, 65807
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104
Saint Louis Cancer and Breast Institute-South City
St Louis, Missouri, 63109
Washington University School of Medicine
St Louis, Missouri, 63110
Saint Louis-Cape Girardeau CCOP
St Louis, Missouri, 63141
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701
Iredell Memorial Hospital
Statesville, North Carolina, 28677
Kaiser Permanente-Stockton
Stockton, California, 95210
Overlook Hospital
Summit, New Jersey, 07902
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, 98405
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467
Kaiser Permanente Medical Center-Vacaville
Vacaville, California, 95688
Kaiser Permanente-Vallejo
Vallejo, California, 94589
Kaiser Permanente-Walnut Creek
Walnut Creek, California, 94596
Saint John Macomb-Oakland Hospital
Warren, Michigan, 48093
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Wenatchee Valley Hospital and Clinics
Wenatchee, Washington, 98801
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803
Southeast Clinical Oncology Research Consortium NCORP
Winston-Salem, North Carolina, 27104
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
Yakima, Washington, 98902
Australia3 sites
Royal Children's Hospital-Brisbane
Herston, Queensland, 4029
Princess Margaret Hospital for Children
Perth, Western Australia, 6008
Queensland Children's Hospital
South Brisbane, Queensland, 4101
Canada3 sites
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, H3H 1P3
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
About this study
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)
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- Conditions
- Anaplastic Astrocytoma, Anaplastic Oligoastrocytoma, Diffuse Intrinsic Pontine Glioma, Gliosarcoma
- Being tested
- 3-Dimensional Conformal Radiation Therapy, Intensity-Modulated Radiation Therapy, Laboratory Biomarker Analysis, Vorinostat
- Medical subject headings
- Astrocytoma, Diffuse Intrinsic Pontine Glioma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
3-Dimensional Conformal Radiation TherapyRadiation
Also called 3-dimensional radiation therapy, 3D Conformal, 3D CONFORMAL RADIATION THERAPY, 3D CRT
Undergo 3D conformal radiation therapy
Intensity-Modulated Radiation TherapyRadiation
Also called IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated Radiotherapy
Undergo intensity-modulated radiation therapy
Laboratory Biomarker AnalysisOther
Correlative studies
VorinostatDrug
Also called L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 Phase I Vorinostat 180 mg/m^2 | Experimental | 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. Receives: Radiation: 3-Dimensional Conformal Radiation Therapy; Radiation: Intensity-Modulated Radiation Therapy; Other: Laboratory Biomarker Analysis; Drug: Vorinostat |
| Arm 2 Phase 1 Vorinostat 230 mg/m^2 | Experimental | 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. Receives: Radiation: 3-Dimensional Conformal Radiation Therapy; Radiation: Intensity-Modulated Radiation Therapy; Other: Laboratory Biomarker Analysis; Drug: Vorinostat |
| Arm 3 Phase II Evaluation Vorinostat 230 mg/m^2 | Experimental | 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. Receives: Radiation: 3-Dimensional Conformal Radiation Therapy; Radiation: Intensity-Modulated Radiation Therapy; Other: Laboratory Biomarker Analysis; Drug: Vorinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Vorinostat
The dose of vorinostat in mg/sqm/day to be administered with combination chemotherapy and radiation therapy
Measured: Planned 7 weeks during chemoradiotherapy
Event-Free Survival
Time from enrollment to disease progression, diagnosis of a second malignant neoplasm, death or last follow-up, whichever occurs first.
Measured: 2 years after study enrollment
Incidence of Toxicity During Chemoradiation Therapy
Proportion of patients who experience any grade 3 or higher CTC AE Version 4 adverse experience
Measured: Planned 7 weeks during chemoradiotherapy
Incidence of Toxicity During Maintenance Therapy
Proportion of patients who experience any grade 3 or higher CTC AE Version 4 adverse experience
Measured: Planned 12 months of maintenance with Vorinostat
Secondary outcomes (4)
Overall Survival
Time from enrollment to death or last follow-up, whichever occurs first.
Measured: 2 years after study enrollment
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.
Measured: Baseline to up to 7 weeks
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.
Measured: Baseline to up to 7 weeks
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.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2010 (estimated)
- Study start9 Aug 2010
- Primary completion30 Jun 2017
- Study completion30 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Anaplastic AstrocytomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 79 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Jack M Su, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01189266
- Sponsor's protocol ID
- NCI-2011-02600
- Other IDs
- NCI-2011-02600, ACNS0927, S12-02793, COG-ACNS0927, CDR0000683459, ACNS0927, ACNS0927, U10CA180886
- Status last verified
- Oct 2021
- First submitted
- 25 Aug 2010
- Last updated
- 28 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01189266
- Acronym / sponsor ID
- NCI-2011-02600
- Conditions
- Anaplastic Astrocytoma, Anaplastic Oligoastrocytoma, Diffuse Intrinsic Pontine Glioma, Gliosarcoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 79 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 9 Aug 2010 (actual)
- Primary completion
- 30 Jun 2017 (actual)
- Study completion
- 30 Sep 2021 (actual)
- First posted
- 26 Aug 2010 (estimated)
- Results
- Posted 3 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 1 Phase I Vorinostat 180 mg/m^2 | Experimental | Radiation: 3-Dimensional Conformal Radiation Therapy, Radiation: Intensity-Modulated Radiation Therapy, Other: Laboratory Biomarker Analysis, Drug: VorinostatPatients 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. |
| Arm 2 Phase 1 Vorinostat 230 mg/m^2 | Experimental | Radiation: 3-Dimensional Conformal Radiation Therapy, Radiation: Intensity-Modulated Radiation Therapy, Other: Laboratory Biomarker Analysis, Drug: VorinostatPatients 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. |
| Arm 3 Phase II Evaluation Vorinostat 230 mg/m^2 | Experimental | Radiation: 3-Dimensional Conformal Radiation Therapy, Radiation: Intensity-Modulated Radiation Therapy, Other: Laboratory Biomarker Analysis, Drug: VorinostatPatients 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. |
Who may qualify
- Ages
- 37 months to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (18 listed)
- 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)
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 3-Dimensional Conformal Radiation TherapyAlso: 3-dimensional radiation therapy, 3D Conformal, 3D CONFORMAL RADIATION THERAPY, 3D CRTUndergo 3D conformal radiation therapy | Radiation | 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 |
| Intensity-Modulated Radiation TherapyAlso: IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated RadiotherapyUndergo intensity-modulated radiation therapy | Radiation | 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 |
| Laboratory Biomarker AnalysisCorrelative studies | Other | 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 |
| VorinostatAlso: L-001079038, MSK-390, SAHA, Suberanilohydroxamic AcidGiven PO | Drug | 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 |
Primary outcome
Maximum Tolerated Dose (MTD) of Vorinostat
Time frame: Planned 7 weeks during chemoradiotherapy
The dose of vorinostat in mg/sqm/day to be administered with combination chemotherapy and radiation therapy
Event-Free Survival
Time frame: 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.
Incidence of Toxicity During Chemoradiation Therapy
Time frame: Planned 7 weeks during chemoradiotherapy
Proportion of patients who experience any grade 3 or higher CTC AE Version 4 adverse experience
Incidence of Toxicity During Maintenance Therapy
Time frame: Planned 12 months of maintenance with Vorinostat
Proportion of patients who experience any grade 3 or higher CTC AE Version 4 adverse experience
4 secondary outcomes
Overall Survival
Time frame: 2 years after study enrollment
Change in H3 and H4 Acetylation Levels in PBMCs
Time frame: Baseline to up to 7 weeks
Change in NHEJ Activity in PBMCs
Time frame: Baseline to up to 7 weeks
Levels of DNA Repair Proteins in Paraffin-embedded Blocks, Measured Via Immunohistochemistry or Western Analysis
Time frame: Baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jack M Su principal investigator
Children's Oncology Group
180 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 3-Dimensional Conformal Radiation Therapy, Intensity-Modulated Radiation Therapy and Laboratory Biomarker Analysis in people with Anaplastic Astrocytoma and Anaplastic Oligoastrocytoma, run by National Cancer Institute (NCI) at 180 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 180 sites in United States, Australia, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) of Vorinostat (time frame: Planned 7 weeks during chemoradiotherapy). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2021.