Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616001350415
Ethics application status
Approved
Date submitted
9/01/2015
Date registered
27/09/2016
Date last updated
27/09/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
the efficacy of histone deacetylase inhibitor valproic acid in the treatment of gliomas
Scientific title
Tolerability and effect of valproate on PET tracer uptake in patients with brain cancer
Secondary ID [1] 285941 0
NIL
Universal Trial Number (UTN)
U1111-1165-8959
Trial acronym
ValCan
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Brain Cancer
 293868 0
Condition category
Condition code
Cancer 294173 294173 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Addition of oral valproate (dose is epilepsy dose titrated to plasma concentration so changes) or placebo to standard care.
start dose is 15-20mg/kg, titrated in 100-200mg amounts depending on clinical status. Once daily until completion of second scan after chemotherapy/radiotherapy scan (3-4 months). VPA commences 4-5 days pre surgery to enable CSF samples at time of surgery. Blood concentrations to monitor adherence.
Intervention code [1] 290918 0
Treatment: Drugs
Comparator / control treatment
EIther they get valproate plus standard treatment (surgery, RT and CT) or standard treatment alone.
Control group
Active

Outcomes
Primary outcome [1] 293965 0
F-DOPA and F-MISO PET uptake using standard PET measurement tool
Timepoint [1] 293965 0
After treatment completed. this includes the chemotherapy (Temozolamide and the RT) and is usually 3-4 months. As the original (standard) pre-op scan is not being done (as too much brain shift to interpret PET volumes accurately post op), the second scan, at the completion of chemo and radiotherapy is the primary time point.
Secondary outcome [1] 312248 0
Possible side effects technically include any reported for VPA over the last 60 years. However we are recording any complaint as reported by the patient and assessing tolerability throughout study (ie any side effects post reporting or querying at any time point) including ECOG status.
Timepoint [1] 312248 0
over course of study - patient can call anytime. They also ha ve the appointments as part of their standard cancer care which are weekly while on chemo and radiation. There is no study followup after the final scan when VPA stops.
Secondary outcome [2] 313840 0
brain tissue for genetic markers known to be associated with survival in brain cancer (e.g. MGMT status and HDAC activity)
Timepoint [2] 313840 0
at time of surgery
Secondary outcome [3] 313841 0
Blood for measurements of valproate concentration, for HDAC activity in the PBMCs and tumor DNA.
Timepoint [3] 313841 0
At time of surgery and then once during the VPA treatment (at the first bleed for VPA concentrations during the chemo/RT)

Eligibility
Key inclusion criteria
GBM and having surgical therapy
Likely to be able to tolerate VPA
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Comorbidities or concurrent drugs making side effects with VPA likely

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation concealment
Patients approached by surgeon pre-surgery and they are consented by a member of the clinical team. The study nurses allocate the treatment randomly and advise the surgeon whether the patient will be having VPA. Allocation was concealed because it involved contacting Clinical trial staff Jacqui Keller or Jennifer Edmunds to provide the next number in the allocation schedule these people are “off-site” in a different building to the Hospital.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised generation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Simple statistical tests measuring uptake of PET tracers and comparing across the two groups, taking into account the baseline

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/01/2013
Actual
1/01/2013
Date of last participant enrolment
Anticipated
31/12/2016
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 3311 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 9094 0
4000 - Brisbane

Funding & Sponsors
Funding source category [1] 290526 0
Charities/Societies/Foundations
Name [1] 290526 0
RBWH Foundation
Country [1] 290526 0
Australia
Primary sponsor type
Hospital
Name
RBWH
Address
RBWH
Herston Rd
Herston
QLD
4006
Country
Australia
Secondary sponsor category [1] 289221 0
None
Name [1] 289221 0
Address [1] 289221 0
Country [1] 289221 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292176 0
Metro North Ethics Committee
Ethics committee address [1] 292176 0
RBWH-Herston
Herston Rd
Herston, QLD 4006
Ethics committee country [1] 292176 0
Australia
Date submitted for ethics approval [1] 292176 0
Approval date [1] 292176 0
30/08/2012
Ethics approval number [1] 292176 0
HREC/12/QRBW/337 *A pilot study of the role of valproate in the treatment of high grade glioma*

Summary
Brief summary
This study will measure the efficacy of valproic acid (VPA), a well established anti-seizure medication with known histone deacetylase (HDAC) inhibitor activity capable of restricting proliferation and inducing differentiation and apoptosis in cancer cells in patients with brain tumours. Who is it for? You may be eligible to join this study if you are aged 18 years or above, have been diagnosed with high grade glioblastoma and are having surgical therapy. Study details All participants will undergo their standard treatment of resection/ radiation therapy and chemotherapy with temozolomide as usual. Participants in this study are randomly allocated (by chance) to one of two groups. Participants in one group will receive valproate in the standard dose used for epilepsy as well as standard care which includes chemotherapy and radiation therapy and surgery as usual. Whilst participants in the other group will receive usual care which includes chemotherapy and radiotherapy and surgery as usual. Participants will undergo diagnostic imaging using 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (FDOPA) PET post surgery and 4 weeks after radiation/chemotherapy has finished, which is the same time as the end of the valproate treatment. Changes on the PET scan which measures activity of the tumour will be measured. Effects of valproate on brain cancer biology will be measured by examining the brain tissue and by measuring cancer markers in the blood.
Trial website
nil
Trial related presentations / publications
Journal of Neuro-oncology 2015 (accepted, in press)
"The effect of valproic acid in combination with irradiation and temozolomide on primary human glioblastoma cells", Hosein, A et al
Public notes

Contacts
Principal investigator
Name 53866 0
Dr Michael Fay
Address 53866 0
Calvary mater Hospital
Department of Oncology
EDith St
Waratah
NSW 2298

Country 53866 0
Australia
Phone 53866 0
+61410681470
Fax 53866 0
Email 53866 0
[email protected]
Contact person for public queries
Name 53867 0
Prof Jennifer Martin
Address 53867 0
University of Newcastle
c/- Level 5, New MED II Building, Calvary Mater Hospital
Edith St
Waratah 2298
NSW
Country 53867 0
Australia
Phone 53867 0
+61405341676
Fax 53867 0
Email 53867 0
[email protected]
Contact person for scientific queries
Name 53868 0
Dr MIchael Fay
Address 53868 0
Calvary mater Hospital
Department of Oncology
EDith St
Waratah
NSW 2298
Country 53868 0
Australia
Phone 53868 0
+61410681470
Fax 53868 0
Email 53868 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIPersistence of DNA adducts, hypermutation and acquisition of cellular resistance to alkylating agents in glioblastoma2017https://doi.org/10.1080/15384047.2017.1385680
N.B. These documents automatically identified may not have been verified by the study sponsor.