Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612001050842
Ethics application status
Not yet submitted
Date submitted
29/09/2012
Date registered
3/10/2012
Date last updated
3/10/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
Valproic acid and Metformin to treat patients with brain tumours
Scientific title
Valproate and MetformIn in GlioBlastoma multiformE Study: A single-arm trial to assess safety and feasibility – VIBE 1
Secondary ID [1] 281322 0
None
Universal Trial Number (UTN)
U1111-1135-2659
Trial acronym
VIBE - 1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Brain tumours - Glioblastoma multiforme (GBM) 287537 0
Condition category
Condition code
Cancer 287862 287862 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Valproic acid and metformin added to standard therapy (Temozolomide/radiotherapy)
Valproic acid: oral - 200 mg twice daily to a maximum of 60 mg/day; dose adjusted based on plasma levels; maximum of 10 months
Metformin: oral titrated upto 2 gm per day; maximum of 10 months
Intervention code [1] 285786 0
Treatment: Drugs
Comparator / control treatment
None - single arm trial
Control group
Uncontrolled

Outcomes
Primary outcome [1] 288084 0
To assess the tolerability and feasibility of adding sodium valproate and metformin to concurrent TMZ+XRT in patients with newly diagnosed GBM.
This outcome will be assessed by clinical examination, blood tests and adverse event monitoring
Timepoint [1] 288084 0
7 weeks from study entry
Secondary outcome [1] 299393 0
1. To assess the safety and feasibility of sodium valproate and metformin added to maintenance TMZ

This outcome will be assessed by clinical examination, blood tests and adverse event monitoring
Timepoint [1] 299393 0
Serially, every month for upto 10 months
Secondary outcome [2] 299394 0
2. Progression free survival
Timepoint [2] 299394 0
6 month
Secondary outcome [3] 299395 0
3. Overall survival
Timepoint [3] 299395 0
12 months from study entry
Secondary outcome [4] 299396 0
4. Objective response rates using Mcdonald's criteria
Timepoint [4] 299396 0
Serial imaging - three monthly scans for 1 year

Eligibility
Key inclusion criteria
1. Newly diagnosed supratentorial GBM (histopathologically confirmed as WHO Grade IV, including GBM subtypes, e.g. gliosarcoma)
2. Males or females older than or equal to 18 years of age.
3. Able to provide written informed consent
4. Stable or decreasing dose of steroids for >5 days prior to randomization.
5. ECOG PS - 0 or 1.
6. Interval of greater than 1 week but less than 7 weeks after surgery or biopsy before first administration of study treatment.
7. Laboratory values (within 2 week prior to randomization):
7.1. Absolute neutrophil count greater than 1500/mm3.
7.2. Platelet count greater than 100,000/mm3.
7.3. Creatinine clearance rate greater than 60 mL/min
7.4. Prothrombin time (PT) international normalized ratio (INR) within normal limits and partial thromboplastin time (PTT) below the upper limit of normal.
7.5. Haemoglobin greater than 10 g/dL.
7.6. Total bilirubin greater than 1.5 x the ULN.
7.7. AST & ALT greater than 2.5 x ULN
7.8. Alkaline phosphatase greater than 2.5 x ULN.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Subjects are not eligible for this study, if they fulfill one or more of the following exclusion criteria:
1. Cytotoxic chemotherapy within the prior 5 years
2. Prior XRT of the head (except for low dose radiotherapy for tinea capitis)
3. Receiving concurrent investigational agents or has received an investigational agent(s) within the past 30 days
4. Prior/current use of metformin or sodium valproate
5. Placement of Gliadel (registered trademark) wafer at surgery.
6. Treatment with a prohibited concomitant medication
7. Planned major surgery for other diseases
8. History of malignancy. Subjects with curatively treated cervical carcinoma in situ or basal cell carcinoma of the skin, or subjects who have been free of other malignancies for more than 5 years are eligible for this study.
9. History of coagulation disorder associated with bleeding or recurrent thromboembolic events.
10. Clinically manifest myocardial insufficiency (NYHA III, IV) or history of myocardial infarction during the past 6 months; uncontrolled arterial hypertension.
11. Concurrent illness, including severe infection,(eg HIV) which may jeopardize the ability of the subject to receive the procedures outlined in this protocol with reasonable safety.
12. Subject is pregnant (positive serum beta human chorionic gonadotropin [beta-HCG] test at screening) or is currently breast-feeding,or has the potential and wishes to becoming pregnant/ impregnate their partner during the study or within 6 months after study participation, or subject does not agree to follow acceptable methods of birth control, such as hormonal contraception, intra-uterine pessary, condoms or sterilization, to avoid conception during the study and for at least 6 months after receiving the last dose of study treatment.
13. Current alcohol dependence or drug abuse.
14. Known hypersensitivity to the study treatment.
15. Unable to adhere to the study protocol or follow-up schedule.
16. Signs and symptoms suggestive of transmissible spongiform encephalopathy, or a family members who suffer(ed) from spongiform encephalopathy.
17. No previous exposure to ALA Fluorescent dye peri operatively

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Eligible subjects will be invited to participate
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Feasibility study
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/01/2013
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
12
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 286084 0
Hospital
Name [1] 286084 0
Flinders Centre for Innovation in Cancer, Flinders University/Flinders Medical centre
Country [1] 286084 0
Australia
Primary sponsor type
Hospital
Name
Flinders Centre for Innovation in Cancer, Flinders University/Flinders Medical centre
Address
Flinders Drive,
Bedford Park,
South Australia - 5042
Country
Australia
Secondary sponsor category [1] 284914 0
None
Name [1] 284914 0
Address [1] 284914 0
Country [1] 284914 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 288136 0
Ethics committee address [1] 288136 0
Ethics committee country [1] 288136 0
Australia
Date submitted for ethics approval [1] 288136 0
15/10/2012
Approval date [1] 288136 0
Ethics approval number [1] 288136 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34775 0
Address 34775 0
Country 34775 0
Phone 34775 0
Fax 34775 0
Email 34775 0
Contact person for public queries
Name 18022 0
Ms Kelly Mead
Address 18022 0
Clinical Oncology Research,
Flinders Centre for Innovation,
Flinders Medical Centre/Flinders University,
Flinders Drive,
Bedford Park,
South Australia - 5042
Country 18022 0
Australia
Phone 18022 0
+61 8 8204 6151
Fax 18022 0
+61 8 8204 4765
Email 18022 0
Kelly.Mead@health.sa.gov.au
Contact person for scientific queries
Name 8950 0
Dr Ganessan Kichenadasse
Address 8950 0
Flinders Centre for Innovation,
Flinders Medical Centre/Flinders University,
Flinders Drive,
Bedford Park,
South Australia - 5042
Country 8950 0
Australia
Phone 8950 0
+61 8 8204 6151
Fax 8950 0
+61 8 8204 4765
Email 8950 0
ganessan.kichenadasse@flinders.edu.au

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
No additional documents have been identified.