valproic acid and Brain Stem Neoplasms, Primary studies

Valproic Acid: A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of EPILEPSY and BIPOLAR DISORDER. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of VOLTAGE-GATED SODIUM CHANNELS.
valproic acid : A branched-chain saturated fatty acid that comprises of a propyl substituent on a pentanoic acid stem.

Research Excerpts

Excerpt	Relevance	Reference
"To study the efficacy and tolerability of valproic acid (VPA) and radiation, followed by VPA and bevacizumab in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG) or high-grade glioma (HGG)."	9.34	A phase 2 study of valproic acid and radiation, followed by maintenance valproic acid and bevacizumab in children with newly diagnosed diffuse intrinsic pontine glioma or high-grade glioma. ( Adesina, AM; Baxter, PA; Blaney, SM; Bowers, DC; Jo, E; McNall-Knapp, RY; Mo, Q; Murray, JC; Paulino, AC; Shah, S; Su, JM, 2020)
"To study the efficacy and tolerability of valproic acid (VPA) and radiation, followed by VPA and bevacizumab in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG) or high-grade glioma (HGG)."	5.34	A phase 2 study of valproic acid and radiation, followed by maintenance valproic acid and bevacizumab in children with newly diagnosed diffuse intrinsic pontine glioma or high-grade glioma. ( Adesina, AM; Baxter, PA; Blaney, SM; Bowers, DC; Jo, E; McNall-Knapp, RY; Mo, Q; Murray, JC; Paulino, AC; Shah, S; Su, JM, 2020)

Research

Studies (3)

Authors

Clinical Trials (1)

Trial Overview

Trial Outcomes

1-year Event Free Survival (EFS)

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	0 (0.00)	29.6817
2010's	2 (66.67)	24.3611
2020's	1 (33.33)	2.80

Authors	Studies
Su, JM	1
Murray, JC	1
McNall-Knapp, RY	1
Bowers, DC	1
Shah, S	1
Adesina, AM	1
Paulino, AC	1
Jo, E	1
Mo, Q	1
Baxter, PA	1
Blaney, SM	1
Killick-Cole, CL	1
Singleton, WGB	1
Bienemann, AS	1
Asby, DJ	1
Wyatt, MJ	1
Boulter, LJ	1
Barua, NU	1
Gill, SS	1
Felix, FH	1
de Araujo, OL	1
da Trindade, KM	1
Trompieri, NM	1
Fontenele, JB	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Phase 2 Study of Valproic Acid and Radiation, Followed by Maintenance Valproic Acid and Bevacizumab in Children With Newly Diagnosed High-grade Gliomas or Brainstem Gliomas[NCT00879437]	Phase 2	38 participants (Actual)	Interventional	2009-09-01	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

To compare 1-year EFS for this trial versus historical series (ACNS0126 for high-grade gliomas; CCG-9941 for DIPG) (NCT00879437)
Timeframe: 12 months

Complete Response in High-grade Gliomas

Intervention	percentage of participants (Number)
Diffuse Intrinsic Pontine Glioma	12
High-grade Gliomas	24

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) (NCT00879437)
Timeframe: up to 24 months

Median Event Free Survival (EFS)

Intervention	Participants (Count of Participants)
High-grade Gliomas	1

estimate the median event free survival of patients receiving protocol therapy (NCT00879437)
Timeframe: 24 months

Median Overall Survival (OS)

Intervention	months (Median)
Diffuse Intrinsic Pontine Glioma	7.8
High-grade Gliomas	9.1

median OS of patients receiving protocol therapy (NCT00879437)
Timeframe: 24 months

Partial Response in Diffuse Intrinsic Pontine Glioma

Intervention	months (Median)
Diffuse Intrinsic Pontine Glioma	10.3
High-grade Gliomas	12.1

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) (NCT00879437)
Timeframe: up to 24 months

Partial Response in High-grade Gliomas

Intervention	Participants (Count of Participants)
Diffuse Intrinsic Pontine Glioma	8

Percentage of Grade 2 Hypertension, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab

Intervention	Participants (Count of Participants)
High-grade Gliomas	5

Document frequency of grade 2 hypertension, assessed by CTCAE v3.0, during maintenance therapy of valproic acid and bevacizumab (NCT00879437)
Timeframe: from week 11 to up to 24 months

Percentage of Participants With Grade 1 Cystitis, Assessed by CTCAE v3.0, During Concurrent Valproic Acid and Radiation Treatment

Intervention	Participants (Count of Participants)
38 Eligible Patients	8

document frequency of grade 2 cystitis, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment from week 1-10 (NCT00879437)
Timeframe: first 10 weeks of therapy

Percentage of Participants With Grade 2 Abdominal Pain, Assessed by CTCAE v3.0, During Concurrent Valproic Acid and Radiation Treatment

Intervention	Participants (Count of Participants)
38 Eligible Patients	1

document frequency of grade 2 abdominal pain, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment, week 1-10 (NCT00879437)
Timeframe: first 10 weeks of therapy

Percentage of Participants With Grade 2 Abdominal Pain, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab

Intervention	Participants (Count of Participants)
38 Eligible Patients	1

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 (NCT00879437)
Timeframe: from week 11 to up to 24 months

Percentage of Participants With Grade 2 Anorexia, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab

Intervention	Participants (Count of Participants)
38 Eligible Patients	1

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 (NCT00879437)
Timeframe: from week 11 to up to 24 months

Percentage of Participants With Grade 2 AST Elevation, Assessed by CTCAE v3.0, During Concurrent Valproic Acid and Radiation Treatment

Intervention	Participants (Count of Participants)
38 Eligible Patients	3

document frequency of grade 2 AST elevation, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment from week 1-10 (NCT00879437)
Timeframe: first 10 weeks of therapy

Percentage of Participants With Grade 2 Cough, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab

Intervention	Participants (Count of Participants)
38 Eligible Patients	1

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 (NCT00879437)
Timeframe: from week 11 to up to 24 months

Percentage of Participants With Grade 2 Fatigue, Assessed by CTCAE v3.0, During Concurrent Valproic Acid and Radiation Treatment

Intervention	Participants (Count of Participants)
38 Eligible Patients	1

document frequency of grade 2 fatigue, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment from week 1-10 (NCT00879437)
Timeframe: first 10 weeks of study

Percentage of Participants With Grade 2 Fatigue, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab

Intervention	Participants (Count of Participants)
38 Eligible Patients	3

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 (NCT00879437)
Timeframe: from week 11 to up to 24 months

Percentage of Participants With Grade 2 Hypoalbuminemia, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab

Intervention	Participants (Count of Participants)
38 Eligible Patients	7

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 (NCT00879437)
Timeframe: from week 11 to up to 24 months

Percentage of Participants With Grade 2 Hypoglycemia, Assessed by CTCAE v3.0, During Concurrent Valproic Acid and Radiation Treatment

Intervention	Participants (Count of Participants)
38 Eligible Patients	3

document frequency of grade 2 hypoglycemia, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment from week 1-10 (NCT00879437)
Timeframe: first 10 weeks of study

Percentage of Participants With Grade 2 Hypoglycemia, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab

Intervention	Participants (Count of Participants)
38 Eligible Patients	1

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 (NCT00879437)
Timeframe: from week 11 to up to 24 months

Percentage of Participants With Grade 2 Intratumoral/Intracranial Hemorrhage, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab

Intervention	Participants (Count of Participants)
38 Eligible Patients	1

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 (NCT00879437)
Timeframe: from week 11 to up to 24 months

Percentage of Participants With Grade 2 Ocular Keratitis, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab

Intervention	Participants (Count of Participants)
38 Eligible Patients	1

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 (NCT00879437)
Timeframe: from week 11 to up to 24 months

Percentage of Participants With Grade 2 Pancreatitis, Assessed by CTCAE v3.0, During Concurrent Valproic Acid and Radiation Treatment

Intervention	Participants (Count of Participants)
38 Eligible Patients	1

document frequency of grade 2 pancreatitis, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment from week 1-10 (NCT00879437)
Timeframe: first 10 weeks of study

Percentage of Participants With Grade 2 Proteinuria, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab

Intervention	Participants (Count of Participants)
38 Eligible Patients	1

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 (NCT00879437)
Timeframe: from week 11 to up to 24 months

Percentage of Participants With Grade 2 Somnolence, Assessed by CTCAE v3.0, During Concurrent Valproic Acid and Radiation Treatment

Intervention	Participants (Count of Participants)
38 Eligible Patients	2

document frequency of grade 2 somnolence, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment from week 1-10 (NCT00879437)
Timeframe: first 10 weeks of study

Percentage of Participants With Grade 2 Somonolence, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab

Intervention	Participants (Count of Participants)
38 Eligible Patients	1

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 (NCT00879437)
Timeframe: from week 11 to up to 24 months

Percentage of Participants With Grade 2 Weight Gain, Assessed by CTCAE v3.0, During Concurrent Valproic Acid and Radiation Treatment

Intervention	Participants (Count of Participants)
38 Eligible Patients	2

document frequency of grade 2 weight gain, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment from week 1-10 (NCT00879437)
Timeframe: first 10 weeks of study

Percentage of Participants With Grade 2 Weight Gain, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab

Intervention	Participants (Count of Participants)
38 Eligible Patients	4

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 (NCT00879437)
Timeframe: from week 11 to up to 24 months

Percentage of Participants With Grade 3 Cellulitis, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab

Intervention	Participants (Count of Participants)
38 Eligible Patients	1

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 (NCT00879437)
Timeframe: from week 11 to up to 24 months

Percentage of Participants With Grade 3 Dehydration, Assessed by CTCAE v3.0, During Concurrent Valproic Acid and Radiation Treatment

Intervention	Participants (Count of Participants)
38 Eligible Patients	1

document frequency of grade 3 dehydration, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment from week 1-10 (NCT00879437)
Timeframe: first 10 weeks of therapy

Percentage of Participants With Grade 3 Fatigue, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab

Intervention	Participants (Count of Participants)
38 Eligible Patients	1

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 (NCT00879437)
Timeframe: from week 11 to up to 24 months

Percentage of Participants With Grade 3 Hypertension, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab

Intervention	Participants (Count of Participants)
38 Eligible Patients	3

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 (NCT00879437)
Timeframe: from week 11 to up to 24 months

Percentage of Participants With Grade 3 Leukopenia, Assessed by CTCAE v3.0, During Concurrent Valproic Acid and Radiation Treatment

Intervention	Participants (Count of Participants)
38 Eligible Patients	4

document frequency of grade 3 leukopenia, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment from week 1-10 (NCT00879437)
Timeframe: first 10 weeks of study

Percentage of Participants With Grade 3 Lipase and Amylase Elevation, Assessed by CTCAE v3.0, During Concurrent Valproic Acid and Radiation Treatment

Intervention	Participants (Count of Participants)
38 Eligible Patients	1

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 (NCT00879437)
Timeframe: first 10 weeks of therapy

Percentage of Participants With Grade 3 Lymphopenia Assessed by CTCAE v3.0 During Concurrent Valproic Acid and Radiation Treatment

Intervention	Participants (Count of Participants)
38 Eligible Patients	1

document frequency of grade 3 lymphopenia, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment from week 1-10 (NCT00879437)
Timeframe: first 10 weeks of study

Percentage of Participants With Grade 3 Lymphopenia, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab

Intervention	Participants (Count of Participants)
38 Eligible Patients	5

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 (NCT00879437)
Timeframe: from week 11 to up to 24 months

Percentage of Participants With Grade 3 Neutropenia Assessed by CTCAE v3.0 During Concurrent Valproic Acid and Radiation Treatment

Intervention	Participants (Count of Participants)
38 Eligible Patients	3

document frequency of grade 3 neutropenia, graded by CTCAE v3.0, during concurrent valproic acid and radiation treatment for the first 10 weeks (NCT00879437)
Timeframe: first 10 weeks of study

Percentage of Participants With Grade 3 Neutropenia, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab

Intervention	Participants (Count of Participants)
38 Eligible Patients	3

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 (NCT00879437)
Timeframe: from week 11 to up to 24 months

Percentage of Participants With Grade 3 Somonolence, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab

Intervention	Participants (Count of Participants)
38 Eligible Patients	3

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 (NCT00879437)
Timeframe: from week 11 to up to 24 months

Percentage of Participants With Grade 3 Subacute Bone Infarction, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab

Intervention	Participants (Count of Participants)
38 Eligible Patients	1

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 (NCT00879437)
Timeframe: from week 11 to up to 24 months

Percentage of Participants With Grade 3 Thrombocytopenia Assessed by CTCAE v3.0 During Concurrent Valproic Acid and Radiation Treatment

Intervention	Participants (Count of Participants)
38 Eligible Patients	1

document frequency of grade 3 thrombocytopenia, graded according to CTCAE v3.0, during concurrent valproic acid and radiation treatment for week 1-10 (NCT00879437)
Timeframe: first 10 weeks of study

Percentage of Participants With Grade 3 Thrombocytopenia, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab

Intervention	Participants (Count of Participants)
38 Eligible Patients	1

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 (NCT00879437)
Timeframe: from week 11 to up to 24 months

Percentage of Participants With Grade 3 Weight Gain, Assessed by CTCAE v3.0, During Concurrent Valproic Acid and Radiation Treatment

Intervention	Participants (Count of Participants)
38 Eligible Patients	3

document frequency of grade 3 weight gain, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment during week 1-10 (NCT00879437)
Timeframe: first 10 weeks of study

Percentage of Participants With Grade 3 Weight Gain, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab

Intervention	Participants (Count of Participants)
38 Eligible Patients	1

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 (NCT00879437)
Timeframe: from week 11 to up to 24 months

Percentage of Participants With Grade 4 Deep Vein Thrombosis, Pulmonary Embolism, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab

Intervention	Participants (Count of Participants)
38 Eligible Patients	2

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 (NCT00879437)
Timeframe: from week 11 to up to 24 months

Percentage of Participants With Grade 4 Radiation Necrosis, Assessed by CTCAE v3.0, During Concurrent Valproic Acid and Radiation Treatment

Intervention	Participants (Count of Participants)
38 Eligible Patients	1

document frequency of grade 4 radiation necrosis, assessed by CTCAE v3.0, during concurrent valproic acid and radiation treatment from week 1-10 (NCT00879437)
Timeframe: first 10 weeks of therapy

Percentage Participants With Grade 2 Urinary Tract Infection, Assessed by CTCAE v3.0, During Maintenance Therapy of Valproic Acid and Bevacizumab

Intervention	Participants (Count of Participants)
38 Eligible Patients	1

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 (NCT00879437)
Timeframe: from week 11 to up to 24 months

Article	Year
Repurposing the anti-epileptic drug sodium valproate as an adjuvant treatment for diffuse intrinsic pontine glioma. PloS one, 2017, Volume: 12, Issue:5 Topics: Acetylation; Adjuvants, Pharmaceutic; Animals; Anticonvulsants; Apoptosis; Brain Stem Neoplasms; Cel	2017
Retrospective evaluation of the outcomes of children with diffuse intrinsic pontine glioma treated with radiochemotherapy and valproic acid in a single center. Journal of neuro-oncology, 2014, Volume: 116, Issue:2 Topics: Adolescent; Antineoplastic Agents; Brain Stem Neoplasms; Carboplatin; Child; Child, Preschool; Femal	2014

valproic acid and Brain Stem Neoplasms, Primary