Trial Outcomes & Findings for Valproic Acid, Radiation, and Bevacizumab in Children With High Grade Gliomas or Diffuse Intrinsic Pontine Glioma (NCT NCT00879437)

NCT ID: NCT00879437

Last Updated: 2021-07-21

Results Overview

To compare 1-year EFS for this trial versus historical series (ACNS0126 for high-grade gliomas; CCG-9941 for DIPG)

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 38 participants
• Primary outcome timeframe: 12 months
• Results posted on: 2021-07-21

Participant Flow

Participants enrolled between September 2009 through August 2015, from five participating sites.

A total of 38 eligible patients, 20 diffuse intrinsic pontine glioma (DIPG), and 18 high-grade glioma (HGG), were enrolled from five institutions.

Participant milestones

Measure	Diffuse Intrinsic Pontine Gliomas (DIPG) Newly diagnosed diffuse intrinsic pontine gliomas; a total of 20 patients enrolled treatment description: radiation phase (week 1-6): daily valproic acid and radiation, for approximately 6 weeks post-radiation phase (week 7-10): valproic acid daily maintenance phase (starting week 11): daily valproic acid, and bevacizumab once every 2 weeks; to continue for a maximum duration of 2 years Valproic acid: Daily (pre-XRT, During XRT, Post-XRT and Maintenance Therapy) Started at 15 mg/kg/day divided into three doses a day as soon as patients have recovered from surgery but no later than the first day of XRT. Dosage will be adjusted in increments of 5 mg/kg/day every 3-5 days to achieve and maintain trough concentrations between 85 and 115 mcg/ml Bevacizumab: All patients will receive bevacizumab (10 mg/kg iv) during the maintenance phase every two weeks for a maximum duration of therapy of 24 months. Radiation therapy: Radiation therapy will start within 30 days of the definitive surgical procedure. Primary brain malignant gliomas will receive a total dose of between 54.0 and 59.4 Gy in 30-33 fractions over 6-7 weeks. Total dose will be 54.0 Gy for completely resected tumors and brainstem gliomas. The total dose will be 59.4 if the tumor is located in the brain but not the brainstem, and the tumor was incompletely resected. Primary spinal cord malignant gliomas will receive a total dose of between 50.4-54 Gy in 28-30 fractions over 5-6 weeks.	High-grade Gliomas (HGG) Newly diagnosed high grade gliomas; a total of 18 patients enrolled treatment description: radiation phase (week 1-6): daily valproic acid and radiation, for approximately 6 weeks post-radiation phase (week 7-10): valproic acid daily maintenance phase (starting week 11): daily valproic acid, and bevacizumab once every 2 weeks; to continue for a maximum duration of 2 years Valproic acid: Daily (pre-XRT, During XRT, Post-XRT and Maintenance Therapy) Started at 15 mg/kg/day divided into three doses a day as soon as patients have recovered from surgery but no later than the first day of XRT. Dosage will be adjusted in increments of 5 mg/kg/day every 3-5 days to achieve and maintain trough concentrations between 85 and 115 mcg/ml Bevacizumab: All patients will receive bevacizumab (10 mg/kg iv) during the maintenance phase every two weeks for a maximum duration of therapy of 24 months. Radiation therapy: Radiation therapy will start within 30 days of the definitive surgical procedure. Primary brain malignant gliomas will receive a total dose of between 54.0 and 59.4 Gy in 30-33 fractions over 6-7 weeks. Total dose will be 54.0 Gy for completely resected tumors and brainstem gliomas. The total dose will be 59.4 if the tumor is located in the brain but not the brainstem, and the tumor was incompletely resected. Primary spinal cord malignant gliomas will receive a total dose of between 50.4-54 Gy in 28-30 fractions over 5-6 weeks.
Overall Study STARTED	20	18
Overall Study COMPLETED	19	17
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Measure	Diffuse Intrinsic Pontine Gliomas (DIPG) Newly diagnosed diffuse intrinsic pontine gliomas; a total of 20 patients enrolled treatment description: radiation phase (week 1-6): daily valproic acid and radiation, for approximately 6 weeks post-radiation phase (week 7-10): valproic acid daily maintenance phase (starting week 11): daily valproic acid, and bevacizumab once every 2 weeks; to continue for a maximum duration of 2 years Valproic acid: Daily (pre-XRT, During XRT, Post-XRT and Maintenance Therapy) Started at 15 mg/kg/day divided into three doses a day as soon as patients have recovered from surgery but no later than the first day of XRT. Dosage will be adjusted in increments of 5 mg/kg/day every 3-5 days to achieve and maintain trough concentrations between 85 and 115 mcg/ml Bevacizumab: All patients will receive bevacizumab (10 mg/kg iv) during the maintenance phase every two weeks for a maximum duration of therapy of 24 months. Radiation therapy: Radiation therapy will start within 30 days of the definitive surgical procedure. Primary brain malignant gliomas will receive a total dose of between 54.0 and 59.4 Gy in 30-33 fractions over 6-7 weeks. Total dose will be 54.0 Gy for completely resected tumors and brainstem gliomas. The total dose will be 59.4 if the tumor is located in the brain but not the brainstem, and the tumor was incompletely resected. Primary spinal cord malignant gliomas will receive a total dose of between 50.4-54 Gy in 28-30 fractions over 5-6 weeks.	High-grade Gliomas (HGG) Newly diagnosed high grade gliomas; a total of 18 patients enrolled treatment description: radiation phase (week 1-6): daily valproic acid and radiation, for approximately 6 weeks post-radiation phase (week 7-10): valproic acid daily maintenance phase (starting week 11): daily valproic acid, and bevacizumab once every 2 weeks; to continue for a maximum duration of 2 years Valproic acid: Daily (pre-XRT, During XRT, Post-XRT and Maintenance Therapy) Started at 15 mg/kg/day divided into three doses a day as soon as patients have recovered from surgery but no later than the first day of XRT. Dosage will be adjusted in increments of 5 mg/kg/day every 3-5 days to achieve and maintain trough concentrations between 85 and 115 mcg/ml Bevacizumab: All patients will receive bevacizumab (10 mg/kg iv) during the maintenance phase every two weeks for a maximum duration of therapy of 24 months. Radiation therapy: Radiation therapy will start within 30 days of the definitive surgical procedure. Primary brain malignant gliomas will receive a total dose of between 54.0 and 59.4 Gy in 30-33 fractions over 6-7 weeks. Total dose will be 54.0 Gy for completely resected tumors and brainstem gliomas. The total dose will be 59.4 if the tumor is located in the brain but not the brainstem, and the tumor was incompletely resected. Primary spinal cord malignant gliomas will receive a total dose of between 50.4-54 Gy in 28-30 fractions over 5-6 weeks.
Overall Study Protocol Violation	0	1
Overall Study Death	1	0

Baseline Characteristics

Valproic Acid, Radiation, and Bevacizumab in Children With High Grade Gliomas or Diffuse Intrinsic Pontine Glioma

Baseline characteristics by cohort

Measure	Valproic Acid and Radiation, Followed by Valproic Acid and Bevacizumab n=38 Participants radiation phase (week 1-6): daily valproic acid and radiation, for approximately 6 weeks post-radiation phase (week 7-10): valproic acid daily maintenance phase (starting week 11): daily valproic acid, and bevacizumab once every 2 weeks; to continue for a maximum duration of 2 years Valproic acid: Daily (pre-XRT, During XRT, Post-XRT and Maintenance Therapy) Started at 15 mg/kg/day divided into three doses a day as soon as patients have recovered from surgery but no later than the first day of XRT. Dosage will be adjusted in increments of 5 mg/kg/day every 3-5 days to achieve and maintain trough concentrations between 85 and 115 mcg/ml Bevacizumab: All patients will receive bevacizumab (10 mg/kg iv) during the maintenance phase every two weeks for a maximum duration of therapy of 24 months. Radiation therapy: Radiation therapy will start within 30 days of the definitive surgical procedure. Primary brain malignant gliomas will receive a total dose of between 54.0 and 59.4 Gy in 30-33 fractions over 6-7 weeks. Total dose will be 54.0 Gy for completely resected tumors and brainstem gliomas. The total dose will be 59.4 if the tumor is located in the brain but not the brainstem, and the tumor was incompletely resected. Primary spinal cord malignant gliomas will receive a total dose of between 50.4-54 Gy in 28-30 fractions over 5-6 weeks.
Age, Categorical <=18 years	37 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants
Race (NIH/OMB) White	29 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	38 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Population: 1 patient with DIPG not evaluable due to early death (did not complete valproic acid and radiation) related to a surgical complication (unrelated to protocol therapy) 1 patient with HGG not evaluable due to non-compliance with protocol therapy

To compare 1-year EFS for this trial versus historical series (ACNS0126 for high-grade gliomas; CCG-9941 for DIPG)

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=19 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas n=17 Participants 18 eligible patients, 17 evaluable patients
1-year Event Free Survival (EFS)	12 percentage of participants Interval 2.0 to 31.0	24 percentage of participants Interval 7.0 to 45.0

PRIMARY outcome

Timeframe: first 10 weeks of study

document frequency of grade 3 thrombocytopenia, graded according to CTCAE v3.0, during concurrent valproic acid and radiation treatment for week 1-10

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 3 Thrombocytopenia Assessed by CTCAE v3.0 During Concurrent Valproic Acid and Radiation Treatment	1 Participants	—

PRIMARY outcome

Timeframe: first 10 weeks of study

document frequency of grade 3 neutropenia, graded by CTCAE v3.0, during concurrent valproic acid and radiation treatment for the first 10 weeks

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 3 Neutropenia Assessed by CTCAE v3.0 During Concurrent Valproic Acid and Radiation Treatment	3 Participants	—

PRIMARY outcome

Timeframe: first 10 weeks of study

document frequency of grade 3 lymphopenia, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment from week 1-10

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 3 Lymphopenia Assessed by CTCAE v3.0 During Concurrent Valproic Acid and Radiation Treatment	5 Participants	—

PRIMARY outcome

Timeframe: first 10 weeks of study

document frequency of grade 3 leukopenia, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment from week 1-10

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 3 Leukopenia, Assessed by CTCAE v3.0, During Concurrent Valproic Acid and Radiation Treatment	1 Participants	—

PRIMARY outcome

Timeframe: first 10 weeks of study

document frequency of grade 2 somnolence, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment from week 1-10

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 2 Somnolence, Assessed by CTCAE v3.0, During Concurrent Valproic Acid and Radiation Treatment	1 Participants	—

PRIMARY outcome

Timeframe: first 10 weeks of study

document frequency of grade 2 fatigue, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment from week 1-10

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 2 Fatigue, Assessed by CTCAE v3.0, During Concurrent Valproic Acid and Radiation Treatment	3 Participants	—

PRIMARY outcome

Timeframe: first 10 weeks of study

document frequency of grade 3 weight gain, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment during week 1-10

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 3 Weight Gain, Assessed by CTCAE v3.0, During Concurrent Valproic Acid and Radiation Treatment	1 Participants	—

PRIMARY outcome

Timeframe: first 10 weeks of study

document frequency of grade 2 weight gain, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment from week 1-10

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 2 Weight Gain, Assessed by CTCAE v3.0, During Concurrent Valproic Acid and Radiation Treatment	4 Participants	—

PRIMARY outcome

Timeframe: first 10 weeks of study

document frequency of grade 2 hypoglycemia, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment from week 1-10

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 2 Hypoglycemia, Assessed by CTCAE v3.0, During Concurrent Valproic Acid and Radiation Treatment	1 Participants	—

PRIMARY outcome

Timeframe: first 10 weeks of therapy

document frequency of grade 3 lipase and amylase elevation, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment from week 1-10

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 3 Lipase and Amylase Elevation, Assessed by CTCAE v3.0, During Concurrent Valproic Acid and Radiation Treatment	1 Participants	—

PRIMARY outcome

Timeframe: first 10 weeks of study

document frequency of grade 2 pancreatitis, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment from week 1-10

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 2 Pancreatitis, Assessed by CTCAE v3.0, During Concurrent Valproic Acid and Radiation Treatment	1 Participants	—

PRIMARY outcome

Timeframe: first 10 weeks of therapy

document frequency of grade 3 dehydration, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment from week 1-10

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 3 Dehydration, Assessed by CTCAE v3.0, During Concurrent Valproic Acid and Radiation Treatment	1 Participants	—

PRIMARY outcome

Timeframe: first 10 weeks of therapy

document frequency of grade 4 radiation necrosis, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment from week 1-10

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 4 Radiation Necrosis, Assessed by CTCAE v3.0, During Concurrent Valproic Acid and Radiation Treatment	1 Participants	—

PRIMARY outcome

Timeframe: first 10 weeks of therapy

document frequency of grade 2 abdominal pain, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment, week 1-10

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 2 Abdominal Pain, Assessed by CTCAE v3.0, During Concurrent Valproic Acid and Radiation Treatment	1 Participants	—

PRIMARY outcome

Timeframe: first 10 weeks of therapy

document frequency of grade 2 AST elevation, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment from week 1-10

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 2 AST Elevation, Assessed by CTCAE v3.0, During Concurrent Valproic Acid and Radiation Treatment	1 Participants	—

PRIMARY outcome

Timeframe: first 10 weeks of therapy

document frequency of grade 2 cystitis, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment from week 1-10

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 1 Cystitis, Assessed by CTCAE v3.0, During Concurrent Valproic Acid and Radiation Treatment	1 Participants	—

PRIMARY outcome

Timeframe: from week 11 to up to 24 months

document frequency of grade 3 thrombocytopenia, assessed by CTCAE v3.0, during maintenance therapy of valproic acid and bevacizumab, from week 11 to 24 months

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 3 Thrombocytopenia, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab	3 Participants	—

PRIMARY outcome

Timeframe: from week 11 to up to 24 months

document frequency of grade 3 neutropenia, assessed by CTCAE v3.0, during maintenance therapy of valproic acid and bevacizumab, from week 11 to up to 24 months

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 3 Neutropenia, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab	3 Participants	—

PRIMARY outcome

Timeframe: from week 11 to up to 24 months

document frequency of grade 3 lymphopenia, assessed by CTCAE v3.0, during maintenance therapy of valproic acid and bevacizumab, from week 11 to up to 24 months

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 3 Lymphopenia, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab	3 Participants	—

PRIMARY outcome

Timeframe: from week 11 to up to 24 months

document frequency of grade 2 intratumoral/intracranial hemorrhage, assessed by CTCAE v3.0, during maintenance therapy of valproic acid and bevacizumab, from week 11 to up to 24 months

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 2 Intratumoral/Intracranial Hemorrhage, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab	1 Participants	—

PRIMARY outcome

Timeframe: from week 11 to up to 24 months

Document frequency of grade 3 fatigue, assessed by CTCAE v3.0, during maintenance therapy of valproic acid and bevacizumab, from week 11 to up to 24 months

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 3 Fatigue, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab	3 Participants	—

PRIMARY outcome

Timeframe: from week 11 to up to 24 months

document frequency of grade 2 or higher fatigue, assessed by CTCAE v3.0, during maintenance therapy of valproic acid and bevacizumab, from week 11 to up to 24 months

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 2 Fatigue, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab	7 Participants	—

PRIMARY outcome

Timeframe: from week 11 to up to 24 months

Document frequency of grade 3 somonolence, assessed by CTCAE v3.0, during maintenance therapy of valproic acid and bevacizumab, from week 11 to up to 24 months

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 3 Somonolence, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab	1 Participants	—

PRIMARY outcome

Timeframe: from week 11 to up to 24 months

document frequency of grade 2 somnolence, assessed by CTCAE v3.0, during maintenance therapy of valproic acid and bevacizumab, from week 11 to up to 24 months

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 2 Somonolence, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab	2 Participants	—

PRIMARY outcome

Timeframe: from week 11 to up to 24 months

Document frequency of grade 3 weight gain, assessed by CTCAE v3.0, during maintenance therapy of valproic acid and bevacizumab, from week 11 to up to 24 months

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 3 Weight Gain, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab	2 Participants	—

PRIMARY outcome

Timeframe: from week 11 to up to 24 months

document frequency of 2 weight gain, assessed by CTCAE v3.0, during maintenance therapy of valproic acid and bevacizumab, from week 11 to up to 24 months

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 2 Weight Gain, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab	1 Participants	—

PRIMARY outcome

Timeframe: from week 11 to up to 24 months

document frequency of grade 3 hypertension, assessed by CTCAE v3.0, during maintenance therapy of valproic acid and bevacizumab, from week 11 to up to 24 months

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 3 Hypertension, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab	4 Participants	—

PRIMARY outcome

Timeframe: from week 11 to up to 24 months

Document frequency of grade 2 hypertension, assessed by CTCAE v3.0, during maintenance therapy of valproic acid and bevacizumab

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Grade 2 Hypertension, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab	8 Participants	—

PRIMARY outcome

Timeframe: from week 11 to up to 24 months

document frequency of grade 2 hypoglycemia, assessed by CTCAE v3.0, during maintenance therapy of valproic acid and bevacizumab, from week 11 to up to 24 months

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 2 Hypoglycemia, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab	1 Participants	—

PRIMARY outcome

Timeframe: from week 11 to up to 24 months

document frequency of grade 3 subacute bone infarction, assessed by CTCAE v3.0, during maintenance therapy of valproic acid and bevacizumab, from week 11 to up to 24 months

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 3 Subacute Bone Infarction, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab	1 Participants	—

PRIMARY outcome

Timeframe: from week 11 to up to 24 months

document frequency of grade 3 cellulitis, assessed by CTCAE v3.0, during maintenance therapy of valproic acid and bevacizumab, from week 11 to up to 24 months

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 3 Cellulitis, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab	1 Participants	—

PRIMARY outcome

Timeframe: from week 11 to up to 24 months

document frequency of grade 2 proteinuria, assessed by CTCAE v3.0, during maintenance therapy of valproic acid and bevacizumab, from week 11 to up to 24 months

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 2 Proteinuria, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab	2 Participants	—

PRIMARY outcome

Timeframe: from week 11 to up to 24 months

document frequency of grade 4 deep vein thrombosis, pulmonary embolism, assessed by CTCAE v3.0, during maintenance therapy of valproic acid and bevacizumab, from week 11 to up to 24 months

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 4 Deep Vein Thrombosis, Pulmonary Embolism, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab	1 Participants	—

PRIMARY outcome

Timeframe: from week 11 to up to 24 months

document frequency of grade 2 ocular keratitis, assessed by CTCAE v3.0, during maintenance therapy of valproic acid and bevacizumab, from week 11 to up to 24 months

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 2 Ocular Keratitis, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab	1 Participants	—

PRIMARY outcome

Timeframe: from week 11 to up to 24 months

document frequency of grade 2 urinary tract infection, assessed by CTCAE v3.0, during maintenance therapy of valproic acid and bevacizumab, from week 11 to up to 24 months

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage Participants With Grade 2 Urinary Tract Infection, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab	1 Participants	—

PRIMARY outcome

Timeframe: from week 11 to up to 24 months

document frequency of grade 2 cough, assessed by CTCAE v3.0, during maintenance therapy of valproic acid and bevacizumab, from week 11 to up to 24 months

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 2 Cough, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab	1 Participants	—

PRIMARY outcome

Timeframe: from week 11 to up to 24 months

document frequency of grade 2 anorexia, assessed by CTCAE v3.0, during maintenance therapy of valproic acid and bevacizumab, from week 11 to up to 24 months

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 2 Anorexia, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab	3 Participants	—

PRIMARY outcome

Timeframe: from week 11 to up to 24 months

document frequency of grade 2 hypoalbuminemia, assessed by CTCAE v3.0, during maintenance therapy of valproic acid and bevacizumab, from week 11 to up to 24 months

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 2 Hypoalbuminemia, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab	3 Participants	—

PRIMARY outcome

Timeframe: from week 11 to up to 24 months

document frequency of grade 2 abdominal pain, assessed by CTCAE v3.0, during maintenance therapy of valproic acid and bevacizumab, from week 11 to up to 24 months

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=38 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Percentage of Participants With Grade 2 Abdominal Pain, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab	1 Participants	—

SECONDARY outcome

Timeframe: 24 months

estimate the median event free survival of patients receiving protocol therapy

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=19 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas n=17 Participants 18 eligible patients, 17 evaluable patients
Median Event Free Survival (EFS)	7.8 months Interval 5.6 to 8.2	9.1 months Interval 6.4 to 11.0

SECONDARY outcome

Timeframe: 24 months

median OS of patients receiving protocol therapy

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=19 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas n=17 Participants 18 eligible patients, 17 evaluable patients
Median Overall Survival (OS)	10.3 months Interval 7.4 to 13.4	12.1 months Interval 10.0 to 22.1

SECONDARY outcome

Timeframe: up to 24 months

partial response defined as 51% to 99% reduction in tumor size,determined using WHO bi-dimensional criteria (product of the greatest tumor diameter and its perpendicular diameter)

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=16 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Partial Response in Diffuse Intrinsic Pontine Glioma	8 Participants	—

SECONDARY outcome

Timeframe: up to 24 months

partial response defined as 51% to 99% reduction in tumor size,determined using WHO bi-dimensional criteria (product of the greatest tumor diameter and its perpendicular diameter)

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=14 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Partial Response in High-grade Gliomas	5 Participants	—

SECONDARY outcome

Timeframe: up to 24 months

complete response defined as complete disappearance of all measurable lesions,determined using WHO bi-dimensional criteria (product of the greatest tumor diameter and its perpendicular diameter)

Outcome measures

Measure	Diffuse Intrinsic Pontine Glioma n=14 Participants 20 eligible patients, 19 evaluable patients	High-grade Gliomas 18 eligible patients, 17 evaluable patients
Complete Response in High-grade Gliomas	1 Participants	—

Adverse Events

38 Eligible Patients

Serious events: 4 serious events

Other events: 33 other events

Deaths: 37 deaths

Serious adverse events

Measure	38 Eligible Patients n=38 participants at risk 38 eligible patients, regardless of tumor type
Nervous system disorders radiation necrosis	2.6% 1/38 • Number of events 1 • up to 24 months
Gastrointestinal disorders amylase and lipase elevation	2.6% 1/38 • Number of events 1 • up to 24 months
Musculoskeletal and connective tissue disorders subacute bone infarction	2.6% 1/38 • Number of events 1 • up to 24 months
Nervous system disorders intratumoral hemorrhage	2.6% 1/38 • Number of events 1 • up to 24 months

Other adverse events

Measure	38 Eligible Patients n=38 participants at risk 38 eligible patients, regardless of tumor type
Blood and lymphatic system disorders thormbocytopenia	7.9% 3/38 • Number of events 5 • up to 24 months
Blood and lymphatic system disorders neutropenia	7.9% 3/38 • Number of events 4 • up to 24 months
Blood and lymphatic system disorders lymphopenia	7.9% 3/38 • Number of events 3 • up to 24 months
Nervous system disorders somnolence	7.9% 3/38 • Number of events 4 • up to 24 months
Nervous system disorders fatigue	26.3% 10/38 • Number of events 11 • up to 24 months
Metabolism and nutrition disorders weight gain	7.9% 3/38 • Number of events 5 • up to 24 months
Cardiac disorders hypertension	31.6% 12/38 • Number of events 18 • up to 24 months
Renal and urinary disorders proteinuria	5.3% 2/38 • Number of events 2 • up to 24 months
Metabolism and nutrition disorders anorexia	7.9% 3/38 • Number of events 3 • up to 24 months
Metabolism and nutrition disorders hypoalbuminemia	7.9% 3/38 • Number of events 3 • up to 24 months

Additional Information

Jack Su

Baylor College of Medicine

Phone: 8328224306

Email: jmsu@txch.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place