Vorinostat and Radiation Therapy Followed by Maintenance... | NCT01189266

NCT01189266

ID	Type	Description	Link
NCI-2011-02600	Registry Identifier	CTRP (Clinical Trial Reporting Program)
ACNS0927
S12-02793
COG-ACNS0927
CDR0000683459
ACNS0927	Other Identifier	Children's Oncology Group
ACNS0927	Other Identifier	CTEP
U10CA180886	U.S. NIH Grant/Contract		View source
U10CA098543	U.S. NIH Grant/Contract		View source
UM1CA097452	U.S. NIH Grant/Contract		View source

Status Module

Description Module

Detailed 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.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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.	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.	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.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
3-Dimensional Conformal Radiation Therapy	Radiation	Undergo 3D conformal radiation therapy	Arm 1 Phase I Vorinostat 180 mg/m^2 Arm 2 Phase 1 Vorinostat 230 mg/m^2

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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
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
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
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 Outcomes

Measure	Description	Time Frame
Overall Survival	Time from enrollment to death or last follow-up, whichever occurs first.	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.

Eligibility Module

Eligibility Criteria

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

Name	Affiliation	Role
Jack M Su	Children's Oncology Group	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Children's Hospital of Alabama		Birmingham	Alabama	35233	United States
University of Alabama at Birmingham Cancer Center

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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. 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

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Aug 6, 2014

Arm/Group Information

ID	Title	Description
BG000	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. 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
BG001	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. 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
BG002	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. 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
BG003	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Maximum Tolerated Dose (MTD) of Vorinostat

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

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.

Posted

Number

mg/m^2

Planned 7 weeks during chemoradiotherapy

ID	Title	Description
OG000	All Phase 1 Study Participants	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).

Units	Counts
Participants	OG00012

Title

Denominators

Categories

Title	Measurements
	OG000230

Primary

Event-Free Survival

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

One patient enrolled on Arm 3 was withdrawn from study prior to the start of treatment.

Posted

Number

95% Confidence Interval

percent probability

2 years after study enrollment

ID	Title	Description
OG000	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. 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
OG001	Arm 2, Phase I 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. 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

Primary

Incidence of Toxicity During Chemoradiation Therapy

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

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.

Posted

Count of Participants

Participants

Planned 7 weeks during chemoradiotherapy

ID	Title	Description
OG000	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. 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
OG001	Arm 2, Phase I 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. 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

Primary

Incidence of Toxicity During Maintenance Therapy

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

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.

Posted

Count of Participants

Participants

Planned 12 months of maintenance with Vorinostat

ID	Title	Description
OG000	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. 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
OG001	Arm 2, Phase I 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. 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

Secondary

Overall Survival

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

One patient enrolled on Arm 3 was withdrawn from study prior to the start of treatment.

Posted

Number

95% Confidence Interval

percent probability

2 years after study enrollment

ID	Title	Description
OG000	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. 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
OG001	Arm 2, Phase I 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. 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

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.

Due to budgetary issues the planned laboratory testing was not performed and no data were collected

Posted

Baseline to up to 7 weeks

ID	Title	Description
OG000	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. 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
OG001	Arm 2, Phase I 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. 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

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.

Due to budgetary issues the planned laboratory testing was not performed and no data were collected

Posted

Baseline to up to 7 weeks

ID	Title	Description
OG000	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. 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
OG001	Arm 2, Phase I 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. 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

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.

Due to budgetary issues the planned laboratory testing was not performed and no data were collected

Posted

Baseline

ID	Title	Description
OG000	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. 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
OG001	Arm 2, Phase I 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. 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

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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. 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	4	6	6	6	6	6
EG001	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. 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	6	6	5	6	6	6
EG002	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. 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	62	65	55	65	51	65

Serious Adverse Events

Term	Organ System	Assessment Type	Notes	Statistical Information
Anemia	Blood and lymphatic system disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0022 events2 affected65 at risk
Blood and lymphatic system disorders - Other, specify	Blood and lymphatic system disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Febrile neutropenia	Blood and lymphatic system disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Abdominal pain	Gastrointestinal disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Dysphagia	Gastrointestinal disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0022 events2 affected65 at risk
Mucositis oral	Gastrointestinal disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0022 events2 affected65 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0021 events1 affected65 at risk
Death NOS	General disorders	Systematic Assessment		EG0003 events3 affected6 at risk EG0012 events2 affected6 at risk EG00234 events34 affected65 at risk
Fatigue	General disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Infusion related reaction	General disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Catheter related infection	Infections and infestations	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Infections and infestations - Other, specify	Infections and infestations	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Lip infection	Infections and infestations	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Lung infection	Infections and infestations	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Sinusitis	Infections and infestations	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Skin infection	Infections and infestations	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Upper respiratory infection	Infections and infestations	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Urinary tract infection	Infections and infestations	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Creatinine increased	Investigations	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Lymphocyte count decreased	Investigations	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0027 events6 affected65 at risk
Neutrophil count decreased	Investigations	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG00210 events9 affected65 at risk
Platelet count decreased	Investigations	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG00210 events9 affected65 at risk
Weight loss	Investigations	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0024 events4 affected65 at risk
White blood cell decreased	Investigations	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0025 events5 affected65 at risk
Anorexia	Metabolism and nutrition disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0023 events3 affected65 at risk
Dehydration	Metabolism and nutrition disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0022 events2 affected65 at risk
Glucose intolerance	Metabolism and nutrition disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Hyperglycemia	Metabolism and nutrition disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0024 events3 affected65 at risk
Hyperkalemia	Metabolism and nutrition disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Hypermagnesemia	Metabolism and nutrition disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0023 events3 affected65 at risk
Hypoalbuminemia	Metabolism and nutrition disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0022 events2 affected65 at risk
Hypokalemia	Metabolism and nutrition disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0022 events2 affected65 at risk
Hyponatremia	Metabolism and nutrition disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Muscle weakness right-sided	Musculoskeletal and connective tissue disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	Other, specific comments provided by the treating physician indicated all the reports were related to the patient's primary diffuse intrinsic pontine brain stem glioma.	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG00211 events11 affected65 at risk
Depressed level of consciousness	Nervous system disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0023 events3 affected65 at risk
Dysarthria	Nervous system disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Headache	Nervous system disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Hydrocephalus	Nervous system disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0023 events3 affected65 at risk
Intracranial hemorrhage	Nervous system disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0023 events3 affected65 at risk
Reversible posterior leukoencephalopathy syndrome	Nervous system disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Seizure	Nervous system disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Somnolence	Nervous system disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0022 events2 affected65 at risk
Spasticity	Nervous system disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Agitation	Psychiatric disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Confusion	Psychiatric disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Hematuria	Renal and urinary disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Urinary retention	Renal and urinary disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0023 events3 affected65 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0023 events3 affected65 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Skin and subcutaneous tissue disorders - Other, specify	Skin and subcutaneous tissue disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Urticaria	Skin and subcutaneous tissue disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Hypertension	Vascular disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0023 events3 affected65 at risk
Thromboembolic event	Vascular disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0022 events2 affected65 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Notes	Statistical Information
Anemia	Blood and lymphatic system disorders	Systematic Assessment		EG00010 events6 affected6 at risk EG0018 events6 affected6 at risk EG0023 events3 affected65 at risk
Chest pain - cardiac	Cardiac disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Mobitz type I	Cardiac disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Palpitations	Cardiac disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Sinus bradycardia	Cardiac disorders	Systematic Assessment		EG0002 events2 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Sinus tachycardia	Cardiac disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Ear pain	Ear and labyrinth disorders	Systematic Assessment		EG0002 events2 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Tinnitus	Ear and labyrinth disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0012 events2 affected6 at risk EG0020 events0 affected65 at risk
Vertigo	Ear and labyrinth disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Adrenal insufficiency	Endocrine disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Cushingoid	Endocrine disorders	Systematic Assessment		EG0002 events2 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Blurred vision	Eye disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0011 events1 affected6 at risk EG0022 events2 affected65 at risk
Conjunctivitis	Eye disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Extraocular muscle paresis	Eye disorders	Systematic Assessment		EG0002 events2 affected6 at risk EG0011 events1 affected6 at risk EG0021 events1 affected65 at risk
Eye disorders - Other, specify	Eye disorders	Systematic Assessment		EG0003 events3 affected6 at risk EG0015 events4 affected6 at risk EG0026 events6 affected65 at risk
Eyelid function disorder	Eye disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0021 events1 affected65 at risk
Photophobia	Eye disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0021 events1 affected65 at risk
Abdominal distension	Gastrointestinal disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Abdominal pain	Gastrointestinal disorders	Systematic Assessment		EG0002 events2 affected6 at risk EG0012 events2 affected6 at risk EG0021 events1 affected65 at risk
Anal pain	Gastrointestinal disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Cheilitis	Gastrointestinal disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Constipation	Gastrointestinal disorders	Systematic Assessment		EG0005 events5 affected6 at risk EG0015 events5 affected6 at risk EG0022 events2 affected65 at risk
Diarrhea	Gastrointestinal disorders	Systematic Assessment		EG0003 events3 affected6 at risk EG0012 events2 affected6 at risk EG0020 events0 affected65 at risk
Dry mouth	Gastrointestinal disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Dyspepsia	Gastrointestinal disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Dysphagia	Gastrointestinal disorders	Systematic Assessment		EG0003 events3 affected6 at risk EG0014 events4 affected6 at risk EG0023 events3 affected65 at risk
Esophageal pain	Gastrointestinal disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0012 events2 affected6 at risk EG0020 events0 affected65 at risk
Fecal incontinence	Gastrointestinal disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Flatulence	Gastrointestinal disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Gastroesophageal reflux disease	Gastrointestinal disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Mucositis oral	Gastrointestinal disorders	Systematic Assessment		EG0003 events3 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment		EG0004 events4 affected6 at risk EG0016 events5 affected6 at risk EG0025 events5 affected65 at risk
Oral hemorrhage	Gastrointestinal disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Stomach pain	Gastrointestinal disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment		EG0008 events5 affected6 at risk EG0017 events5 affected6 at risk EG0026 events6 affected65 at risk
Chills	General disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Fatigue	General disorders	Systematic Assessment		EG0005 events5 affected6 at risk EG0018 events6 affected6 at risk EG00210 events9 affected65 at risk
Fever	General disorders	Systematic Assessment		EG0003 events3 affected6 at risk EG0010 events0 affected6 at risk EG0022 events2 affected65 at risk
Flu like symptoms	General disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Gait disturbance	General disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0013 events3 affected6 at risk EG0025 events5 affected65 at risk
General disorders and administration site conditions - Other, specify	General disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0022 events2 affected65 at risk
Irritability	General disorders	Systematic Assessment		EG0004 events2 affected6 at risk EG0011 events1 affected6 at risk EG0023 events3 affected65 at risk
Malaise	General disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0022 events2 affected65 at risk
Pain	General disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Allergic reaction	Immune system disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Bladder infection	Infections and infestations	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Bronchial infection	Infections and infestations	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Conjunctivitis infective	Infections and infestations	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Infections and infestations - Other, specify	Infections and infestations	Systematic Assessment		EG0002 events2 affected6 at risk EG0011 events1 affected6 at risk EG0022 events2 affected65 at risk
Lip infection	Infections and infestations	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Mucosal infection	Infections and infestations	Systematic Assessment		EG0001 events1 affected6 at risk EG0013 events2 affected6 at risk EG0022 events2 affected65 at risk
Otitis media	Infections and infestations	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Sinusitis	Infections and infestations	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Skin infection	Infections and infestations	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Upper respiratory infection	Infections and infestations	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Wound infection	Infections and infestations	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Bruising	Injury, poisoning and procedural complications	Systematic Assessment		EG0001 events1 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Dermatitis radiation	Injury, poisoning and procedural complications	Systematic Assessment		EG0002 events2 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Injury, poisoning and procedural complications - Other, specify	Injury, poisoning and procedural complications	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Alanine aminotransferase increased	Investigations	Systematic Assessment		EG0007 events6 affected6 at risk EG0014 events4 affected6 at risk EG0023 events3 affected65 at risk
Alkaline phosphatase increased	Investigations	Systematic Assessment		EG0002 events2 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Aspartate aminotransferase increased	Investigations	Systematic Assessment		EG0003 events3 affected6 at risk EG0011 events1 affected6 at risk EG0021 events1 affected65 at risk
Blood bilirubin increased	Investigations	Systematic Assessment		EG0005 events3 affected6 at risk EG0012 events2 affected6 at risk EG0020 events0 affected65 at risk
Cholesterol high	Investigations	Systematic Assessment		EG0001 events1 affected6 at risk EG0011 events1 affected6 at risk EG0022 events2 affected65 at risk
Creatinine increased	Investigations	Systematic Assessment		EG0005 events5 affected6 at risk EG0012 events2 affected6 at risk EG0023 events3 affected65 at risk
GGT increased	Investigations	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Investigations - Other, specify	Investigations	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Lipase increased	Investigations	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Lymphocyte count decreased	Investigations	Systematic Assessment		EG00015 events6 affected6 at risk EG0019 events5 affected6 at risk EG0029 events9 affected65 at risk
Lymphocyte count increased	Investigations	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Neutrophil count decreased	Investigations	Systematic Assessment		EG0008 events5 affected6 at risk EG0016 events4 affected6 at risk EG0029 events8 affected65 at risk
Platelet count decreased	Investigations	Systematic Assessment		EG00010 events5 affected6 at risk EG0016 events5 affected6 at risk EG0027 events7 affected65 at risk
Serum amylase increased	Investigations	Systematic Assessment		EG0002 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Weight gain	Investigations	Systematic Assessment		EG0002 events2 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Weight loss	Investigations	Systematic Assessment		EG0000 events0 affected6 at risk EG0012 events2 affected6 at risk EG0022 events2 affected65 at risk
White blood cell decreased	Investigations	Systematic Assessment		EG00012 events6 affected6 at risk EG0017 events4 affected6 at risk EG0029 events8 affected65 at risk
Anorexia	Metabolism and nutrition disorders	Systematic Assessment		EG0004 events4 affected6 at risk EG0015 events4 affected6 at risk EG0022 events2 affected65 at risk
Dehydration	Metabolism and nutrition disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0022 events2 affected65 at risk
Hypercalcemia	Metabolism and nutrition disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Hyperglycemia	Metabolism and nutrition disorders	Systematic Assessment		EG0005 events4 affected6 at risk EG0016 events4 affected6 at risk EG0026 events6 affected65 at risk
Hyperkalemia	Metabolism and nutrition disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0021 events1 affected65 at risk
Hypermagnesemia	Metabolism and nutrition disorders	Systematic Assessment		EG0004 events4 affected6 at risk EG0016 events6 affected6 at risk EG0023 events3 affected65 at risk
Hypernatremia	Metabolism and nutrition disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Hypertriglyceridemia	Metabolism and nutrition disorders	Systematic Assessment		EG0002 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Hypoalbuminemia	Metabolism and nutrition disorders	Systematic Assessment		EG0004 events3 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Hypocalcemia	Metabolism and nutrition disorders	Systematic Assessment		EG0002 events2 affected6 at risk EG0012 events2 affected6 at risk EG0022 events2 affected65 at risk
Hypoglycemia	Metabolism and nutrition disorders	Systematic Assessment		EG0003 events2 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Hypokalemia	Metabolism and nutrition disorders	Systematic Assessment		EG0005 events5 affected6 at risk EG0011 events1 affected6 at risk EG0024 events4 affected65 at risk
Hyponatremia	Metabolism and nutrition disorders	Systematic Assessment		EG0002 events2 affected6 at risk EG0013 events3 affected6 at risk EG0024 events4 affected65 at risk
Hypophosphatemia	Metabolism and nutrition disorders	Systematic Assessment		EG0003 events3 affected6 at risk EG0012 events2 affected6 at risk EG0021 events1 affected65 at risk
Metabolism and nutrition disorders - Other, specify	Metabolism and nutrition disorders	Systematic Assessment		EG0002 events1 affected6 at risk EG0012 events2 affected6 at risk EG0020 events0 affected65 at risk
Back pain	Musculoskeletal and connective tissue disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Muscle weakness left-sided	Musculoskeletal and connective tissue disorders	Systematic Assessment		EG0005 events3 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Muscle weakness lower limb	Musculoskeletal and connective tissue disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Muscle weakness right-sided	Musculoskeletal and connective tissue disorders	Systematic Assessment		EG0002 events2 affected6 at risk EG0012 events2 affected6 at risk EG0026 events6 affected65 at risk
Muscle weakness upper limb	Musculoskeletal and connective tissue disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0022 events2 affected65 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0012 events2 affected6 at risk EG0020 events0 affected65 at risk
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	Other, specific comments provided by the treating physician indicated all the reports were related to the patient's primary diffuse intrinsic pontine brain stem glioma	EG0001 events1 affected6 at risk EG0013 events3 affected6 at risk EG00213 events13 affected65 at risk
Abducens nerve disorder	Nervous system disorders	Systematic Assessment		EG0002 events2 affected6 at risk EG0012 events2 affected6 at risk EG00212 events12 affected65 at risk
Accessory nerve disorder	Nervous system disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Amnesia	Nervous system disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Ataxia	Nervous system disorders	Systematic Assessment		EG0006 events6 affected6 at risk EG0016 events6 affected6 at risk EG00219 events19 affected65 at risk
Concentration impairment	Nervous system disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Dizziness	Nervous system disorders	Systematic Assessment		EG0002 events2 affected6 at risk EG0010 events0 affected6 at risk EG0023 events3 affected65 at risk
Dysarthria	Nervous system disorders	Systematic Assessment		EG0006 events5 affected6 at risk EG0011 events1 affected6 at risk EG00213 events12 affected65 at risk
Dysgeusia	Nervous system disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Dysphasia	Nervous system disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Extrapyramidal disorder	Nervous system disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Facial muscle weakness	Nervous system disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0025 events5 affected65 at risk
Facial nerve disorder	Nervous system disorders	Systematic Assessment		EG0003 events3 affected6 at risk EG0013 events3 affected6 at risk EG00212 events12 affected65 at risk
Glossopharyngeal nerve disorder	Nervous system disorders	Systematic Assessment		EG0002 events1 affected6 at risk EG0010 events0 affected6 at risk EG0023 events3 affected65 at risk
Headache	Nervous system disorders	Systematic Assessment		EG0004 events4 affected6 at risk EG0016 events5 affected6 at risk EG0029 events9 affected65 at risk
Hydrocephalus	Nervous system disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0026 events5 affected65 at risk
Hypoglossal nerve disorder	Nervous system disorders	Systematic Assessment		EG0002 events2 affected6 at risk EG0010 events0 affected6 at risk EG0022 events2 affected65 at risk
Intracranial hemorrhage	Nervous system disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Lethargy	Nervous system disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Nervous system disorders - Other, specify	Nervous system disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0012 events1 affected6 at risk EG0025 events5 affected65 at risk
Nystagmus	Nervous system disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0012 events2 affected6 at risk EG0023 events3 affected65 at risk
Paresthesia	Nervous system disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0012 events2 affected6 at risk EG0020 events0 affected65 at risk
Peripheral motor neuropathy	Nervous system disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0011 events1 affected6 at risk EG0021 events1 affected65 at risk
Peripheral sensory neuropathy	Nervous system disorders	Systematic Assessment		EG0002 events2 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Pyramidal tract syndrome	Nervous system disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0022 events2 affected65 at risk
Seizure	Nervous system disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0022 events2 affected65 at risk
Spasticity	Nervous system disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Tremor	Nervous system disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Trigeminal nerve disorder	Nervous system disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Vagus nerve disorder	Nervous system disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0012 events1 affected6 at risk EG0021 events1 affected65 at risk
Agitation	Psychiatric disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0011 events1 affected6 at risk EG0023 events2 affected65 at risk
Anxiety	Psychiatric disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0011 events1 affected6 at risk EG0021 events1 affected65 at risk
Confusion	Psychiatric disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Depression	Psychiatric disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0012 events2 affected6 at risk EG0020 events0 affected65 at risk
Insomnia	Psychiatric disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0013 events2 affected6 at risk EG0021 events1 affected65 at risk
Personality change	Psychiatric disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0021 events1 affected65 at risk
Psychiatric disorders - Other, specify	Psychiatric disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Bladder spasm	Renal and urinary disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Hematuria	Renal and urinary disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Renal and urinary disorders - Other, specify	Renal and urinary disorders	Systematic Assessment		EG0002 events2 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Urinary incontinence	Renal and urinary disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Urinary retention	Renal and urinary disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0012 events2 affected6 at risk EG0021 events1 affected65 at risk
Urinary tract pain	Renal and urinary disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Allergic rhinitis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Apnea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment		EG0004 events4 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment		EG0002 events2 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment		EG0002 events2 affected6 at risk EG0012 events2 affected6 at risk EG0020 events0 affected65 at risk
Hiccups	Respiratory, thoracic and mediastinal disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	Systematic Assessment		EG0002 events2 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Respiratory, thoracic and mediastinal disorders - Other, specify	Respiratory, thoracic and mediastinal disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0021 events1 affected65 at risk
Sneezing	Respiratory, thoracic and mediastinal disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Sore throat	Respiratory, thoracic and mediastinal disorders	Systematic Assessment		EG0002 events2 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Alopecia	Skin and subcutaneous tissue disorders	Systematic Assessment		EG0002 events2 affected6 at risk EG0013 events3 affected6 at risk EG0020 events0 affected65 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Pruritus	Skin and subcutaneous tissue disorders	Systematic Assessment		EG0002 events2 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Rash acneiform	Skin and subcutaneous tissue disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	Systematic Assessment		EG0003 events3 affected6 at risk EG0012 events2 affected6 at risk EG0021 events1 affected65 at risk
Skin and subcutaneous tissue disorders - Other, specify	Skin and subcutaneous tissue disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Skin hypopigmentation	Skin and subcutaneous tissue disorders	Systematic Assessment		EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected65 at risk
Surgical and medical procedures - Other, specify	Surgical and medical procedures	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk
Hematoma	Vascular disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Hot flashes	Vascular disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected65 at risk
Hypertension	Vascular disorders	Systematic Assessment		EG0007 events5 affected6 at risk EG0013 events2 affected6 at risk EG0022 events2 affected65 at risk
Hypotension	Vascular disorders	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected65 at risk

ID	Term
D001254	Astrocytoma
D000080443	Diffuse Intrinsic Pontine Glioma
D018316	Gliosarcoma

ID	Term
D005910	Glioma
D018302	Neoplasms, Neuroepithelial
D017599	Neuroectodermal Tumors
D009373	Neoplasms, Germ Cell and Embryonal
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D009375	Neoplasms, Glandular and Epithelial
D009380	Neoplasms, Nerve Tissue
D020295	Brain Stem Neoplasms
D015192	Infratentorial Neoplasms
D001932	Brain Neoplasms
D016543	Central Nervous System Neoplasms
D009423	Nervous System Neoplasms
D009371	Neoplasms by Site
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases

ID	Term
D020266	Radiotherapy, Conformal
D050397	Radiotherapy, Intensity-Modulated
D000077337	Vorinostat

ID	Term
D011881	Radiotherapy, Computer-Assisted
D011878	Radiotherapy
D013812	Therapeutics
D000813	Anilides
D000577	Amides
D009930	Organic Chemicals
D000814	Aniline Compounds
D000588	Amines
D006877	Hydroxamic Acids
D006898	Hydroxylamines
D006880	Hydroxy Acids
D002264	Carboxylic Acids