5-ALA in bowel cancer surgery

ISRCTN	ISRCTN79949827
DOI	https://doi.org/10.1186/ISRCTN79949827
Clinical Trials Information System (CTIS)	2012-002623-15
Protocol serial number	14209; EME 11/100/24
Sponsor	University of Leeds (UK)
Funder	Efficacy and Mechanism Evaluation Programme

Submission date: 04/04/2013
Registration date: 04/04/2013
Last edited: 25/04/2019

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

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-of-5ala-in-bowel-cancer-surgery-glisten

Contact information

Prof David Jayne
Scientific

University of Leeds & Leeds Teaching Hospitals NHS Trust
Section of Translational Anaesthesia & Surgery
Beckett Street
Leeds
LS9 7TF
United Kingdom

Email	d.g.jayne@leeds.ac.uk

Study information

Primary study design	Interventional
Study design	Non-randomised; Interventional; Design type: Treatment
Secondary study design	Non randomised study
Study type	Participant information sheet
Scientific title	GLiSten: Next generation intraoperative lymph node staging for stratified colon cancer surgery - development phase
Study acronym	GLiSten
Study objectives	The study is looking at the use of 5-aminolevulinic acid (5-ALA) in bowel cancer. 5-ALA will not be used to treat the cancer but used during the operation to detect the cancer along with any spread to lymph nodes that surround the bowel as it is preferentially taken up into cancer cells. More details can be found at: https://www.journalslibrary.nihr.ac.uk/programmes/eme/1110024/#/ Protocol can be found at: https://njl-admin.nihr.ac.uk/document/download/2005810
Ethics approval(s)	NRES Committee London - South East, 20/03/2013, ref: 13/LO/0214
Health condition(s) or problem(s) studied	Topic: National Cancer Research Network; Subtopic: Colorectal Cancer; Disease: Colon
Intervention	5-ALA will be given as a drink approximately 4 hours before surgery and it is thought that any cancer cells in the bowel and in the lymph nodes will glow red under a blue light. The surgical specimen will be pathologically reviewed and the areas with confirmed cancer cells will be compared to areas that glowed red to see how accurately the substance (5-ALA) detects bowel cancer. 5-ALA has been used extensively before in other cancers, such as bladder cancer, brain tumours, and ovarian cancer. It has only been used before on a very small scale in colorectal cancer. The study will first run as a Development phase to standardize the techniques, in two centres (Leeds and Dublin), recruiting at least 30 patients with positive lymph nodes. The trial will then expand to an Evaluation phase at approximately 8 centres recruiting 300 patients. Follow Up Length: 1 month(s)
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	5-aminolevulinic acid
Primary outcome measure(s)	Identification of the optimal dose for oral administration of 5-ALA for the accurate intra-operative; Timepoint(s): November 2014
Key secondary outcome measure(s)	1. Standardisation of preoperative CT reporting, with emphasis on lymph node evaluation 2. Standardisation of operative procedure including D3 lymphadenectomy 3. Optimisation and standardisation of fluorescence detection system 4. Standardisation of pathological lymph node mapping and step sectioning for in depth lymph node evaluation 5. Patient factors affecting the accuracy of 5-ALA fluorescence diagnosis 6. Safety
Completion date	30/11/2014

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	52
Key inclusion criteria	1. Able to give informed consent and willing to follow trial protocol 2. Aged over 18 3. Patients with cancers of the right and sigmoid colon amenable to laparoscopic resection incorporating D3 lymphadenectomy, as agreed by MDT discussion following histopathological diagnosis and radiological staging. Where possible, the study population will be enriched with locally advanced colon cancers to obtain as much information as possible on 5-ALA Fluorescence diagnosi (FD) for lymph node metastases 4. Patients with distant metastatic disease will be eligible, provided laparoscopic resection of the cancer is part of routine clinical care 5. Fit for standard laparoscopic resection 6. American Society of Anesthesiologists (ASA) classification <= 3 7. Normal hepatic and renal function 7.1. Total bilirubin within normal institutional limits, AST/ALT < 2.5 X institutional upper limit of normal 7.2. Creatinine within normal institutional limits
Key exclusion criteria	1. Patients with cancers of the transverse and left colon (due to difficulty in defining D3 lymphadenectomy in these anatomical locations) 2. Past history of hypersensitivity reactions to 5-ALA or colorimetric dye 3. Acute or chronic porphyria or a family history 4. Patients with synchronous colonic or rectal cancer (but not benign polyps) 5. Patients with coexistent inflammatory bowel disease, such as Crohns disease, ulcerative colitis or active diverticulitis, which may influence the lymphatic uptake of 5-ALA 6. Pregnant (positive pregnancy test) or breast feeding. 5-ALA has unknown teratogenic and abortifacient effects. 7. Received an investigational medicinal product at any dose within 28 days before registration 8. Poorly controlled or serious medical or psychiatric illness that, in the Investigators opinion, is likely to interfere with participation and/or compliance in this clinical trial
Date of first enrolment	01/06/2013
Date of final enrolment	30/11/2014

Locations

Countries of recruitment

United Kingdom
England
Ireland

Study participating centre

University of Leeds & Leeds Teaching Hospitals NHS Trust

Leeds
LS9 7TF
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/08/2016		Yes	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Plain English results				No	Yes

Editorial Notes

25/04/2019: Cancer Research UK lay results summary link added to Results (plain English).
24/01/2017: Publication reference added.