Clinical trial NCT01861990: Valproic Acid in Childhood Progressive Brain Tumors
Official title: Valproic Acid for Children With Recurrent and Progressive Brain Tumors
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Pediatric Brain Tumor
Glioma
Anaplastic Astrocytoma
Medulloblastoma
Glioblastoma
Keywords: Glioma
Glioblastoma
Pediatric
Child
Brain tumor
Astrocytoma
Medulloblastoma
PNET
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
First posted: 2013-05-24
Enrollment: 0
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study investigates valproic acid added to radiation and temozolomide therapy (standard of care) for progressive or recurrent pediatric brain tumors.

Detailed description: Patients with progressive or recurrent pediatric brain tumors are administered valproic acid, an HDAC inhibitor, along with standard of care therapy (radiation and temozolomide) for induction therapy. Thereafter, patients will be able to continue on valproic acid and temozolomide therapy as long as the combination is well tolerated and the tumor is not progressing.

Eligibility criteria: Inclusion Criteria:

* Subject, parent, or guardian willing and able to give informed consent
* Recurrent or progressive pediatric brain tumor, with MRI evidence of disease
* Age at first diagnosis of brain tumor 1-21 years old
* Lansky or Karnofsky performance score of at least 50 at diagnosis

Exclusion Criteria:

* Pregnancy
* Prior intolerance to valproic acid
* History of use of temozolomide
* Use of enzyme inducing anticonvulsant medications (see appendix B)
* Known urea cycle disorder (e.g. ornithine transcarbamylase deficiency)

Primary outcomes:
measure: Completion of protocol
timeFrame: 2 months
Secondary outcomes:
measure: Time to progression
timeFrame: 2 months
Other outcomes:
Locations:
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: Medical University of South Carolina
name: Amy L Bredlau, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Van Nifterik KA, Van den Berg J, Slotman BJ, Lafleur MV, Sminia P, Stalpers LJ. Valproic acid sensitizes human glioma cells for temozolomide and gamma-radiation. J Neurooncol. 2012 Mar;107(1):61-7. doi: 10.1007/s11060-011-0725-z. Epub 2011 Oct 26.
citation: Asklund T, Kvarnbrink S, Holmlund C, Wibom C, Bergenheim T, Henriksson R, Hedman H. Synergistic killing of glioblastoma stem-like cells by bortezomib and HDAC inhibitors. Anticancer Res. 2012 Jul;32(7):2407-13.
citation: Fu J, Shao CJ, Chen FR, Ng HK, Chen ZP. Autophagy induced by valproic acid is associated with oxidative stress in glioma cell lines. Neuro Oncol. 2010 Apr;12(4):328-40. doi: 10.1093/neuonc/nop005. Epub 2009 Oct 15.
citation: Weller M, Gorlia T, Cairncross JG, van den Bent MJ, Mason W, Belanger K, Brandes AA, Bogdahn U, Macdonald DR, Forsyth P, Rossetti AO, Lacombe D, Mirimanoff RO, Vecht CJ, Stupp R. Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma. Neurology. 2011 Sep 20;77(12):1156-64. doi: 10.1212/WNL.0b013e31822f02e1. Epub 2011 Aug 31.
citation: Masoudi A, Elopre M, Amini E, Nagel ME, Ater JL, Gopalakrishnan V, Wolff JE. Influence of valproic acid on outcome of high-grade gliomas in children. Anticancer Res. 2008 Jul-Aug;28(4C):2437-42.