An evaluation of the tolerability and feasibility of combining 5-Amino-Levulinic Acid (5-ALA) with carmustine wafers (Gliadel) in the surgical management of primary Glioblastoma

ISRCTN	ISRCTN77105850
DOI	https://doi.org/10.1186/ISRCTN77105850
EudraCT/CTIS number	2010-022496-66
ClinicalTrials.gov number	NCT01310868
Secondary identifying numbers	9566

Submission date: 21/06/2011
Registration date: 21/06/2011
Last edited: 14/05/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://cancerhelp.cancerresearchuk.org/trials/a-trial-looking-at-5ala-and-gliadel-wafers-as-part-of-treatment-for-glioblastoma-gala5

Study website

Contact information

Dr Fiona Dungey
Scientific

Cancer Research UK & UCL Cancer Trials Centre
90 Tottenham Court Road
London
W1T 4TJ
United Kingdom

Study information

Study design	Non-randomised interventional treatment trial
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	An evaluation of the tolerability and feasibility of combining 5-Amino-Levulinic Acid (5-ALA) with carmustine wafers (Gliadel) in the surgical management of primary Glioblastoma (GALA-5 Trial)
Study acronym	GALA-5
Study objectives	Glioblastoma (GBM) is the commonest brain tumour in adults. The combination of surgical cytoreduction (removal of the tumour), concomitant chemoradiation (chemotherapy given at the same time as radiotherapy) and adjuvant chemotherapy (chemotherapy given after the chemoradiotherapy leads to a median survival of 15 months and 2 year survival of 27%. Aminolevulinic acid hydrochloride (5-aminolevulinic acid HCl; 5ALA; Gliolan) is a prodrug that leads to the selective accumulation of the fluorescent compound protoporphyrin IX (PPIX) in GBM. This can be visualised under blue light enabling objective surgical resection and improved progression free survival. Carmustine wafers (Gliadel) are biodegradable copolymer discs impregnated with the alkylating agent carmustine that are implanted into the resection cavity at the end of surgery. They have a modest impact on survival of GBM patients but have yet to be evaluated in combination with fluorescence guided resection. The aim of this study is to establish the safety, tolerability and feasibility of combining fluorescence-guided surgical tumour resection with intraoperative chemotherapy in GBM patients eligible to proceed onto chemoradiotherapy. Patients with suspected primary GBM in whom complete resection is considered feasible will be given 5-ALA. They will then receive carmustine implants. A protocol summary can be downloaded from the trial website: http://www.ctc.ucl.ac.uk/TrialDetails.aspx?TrialID=50 More details can be found here: http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=9566
Ethics approval(s)	10/H0304/100
Health condition(s) or problem(s) studied	Topic: National Cancer Research Network; Subtopic: Brain Tumour; Disease: Brain and Nervous System
Intervention	1. 60 patients are required to receive both Gliolan and Gliadel wafers for the trial 2. The trial will stop recruiting once 60 patients have received both treatments 3. The global sample size has been set at 120 patients on the portfolio to account for a 50% rate of failure to administer Gliadel wafers (e.g to patients with complications or those who are found to be ineligible during surgery) 4. 5-ALA (Gliolan) used to guide resection 5. Gliadel wafers are inserted into tumour cavity at the end of resection
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	Gliolan, Gliadel
Primary outcome measure	1. % 5-ALA resected patients receiving Carmustine wafers 2. Post operative complication rate 3. No. patients with delay (> 6 weeks) to receiving chemoRT due to surgical complications 4. No. patients failing to receive chemoRT due to surgical complications 5. No. patients failing to complete chemoRT without interruption 6. % patients with a lower WHO performance status after surgery with Carmustine wafers
Secondary outcome measures	1. Time to Clinical Progression 2. Survival at 24 months
Overall study start date	01/05/2011
Completion date	01/05/2013

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	UK Sample Size: 120
Key inclusion criteria	1. The patient is reviewed at a specialist neuro-oncology multi-disciplinary team (MDT). 2. Preop MRI should be carried out, ideally on no or stable steroids according to RANO criteria 3. Imaging is evaluated by a neuro-radiologist and judged to have typical appearances of a primary GBM 4. Radical resection is judged to be realistic by the neurosurgeons at the MDT (i.e. NICE criteria for the use of Carmustine wafers can be met) 5. WHO performance status 0 or 1 6. Age ≥18 7. Patient judged by MDT to be fit for standard radical aggressive therapy for GBM (resection followed by RT with concomitant and adjuvant temozolomide)
Key exclusion criteria	1. GBM thought to be transformed low grade or secondary disease 2. The patient has not been seen by a specialist MDT. 3. There is uncertainty about the radiological diagnosis 4. 5-ALA or Carmustine wafers is contra-indicated (inc known or suspected allergies to 5-ALA or porphyrins, or acute or chronic types of porphyria) 5. Pregnant or lactating women 6. Known or suspected HIV or other significant infection or comorbidity that would preclude radical aggressive therapy for GBM 7. Active liver disease (ALT or AST ≥5 x ULRR) 8. Concomitant anti-cancer therapy except steroids 9. History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within 5 years 10. Previous brain surgery (including biopsy) or cranial radiotherapy 11. Platelets <100 x109/L 12. Mini mental status score <15
Date of first enrolment	01/05/2011
Date of final enrolment	01/05/2013

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Cancer Research UK & UCL Cancer Trials Centre

London
W1T 4TJ
United Kingdom

Sponsor information

University College London (UK)
University/education

Gower Street
London
WC1E 6BT
England
United Kingdom

Website	http://www.ucl.ac.uk/
"ROR"	https://ror.org/02jx3x895

Funders

Funder type

Charity

Cancer Research UK
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

Samantha Dickson Brain Tumour Trust
Private sector organisation / Other non-profit organizations

Alternative name(s): SDBTT
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Basic results				No	No
HRA research summary			28/06/2023	No	No

Editorial Notes

14/05/2019: Added ClinicalTrials.gov and EudraCT links to basic results (scientific).
06/03/2018: No publications found, verifying study status with principal investigator.
16/02/2016: No publications found, verifying study status with principal investigator.