Contact information
Type
Scientific
Primary contact
Dr M W Reed
ORCID ID
Contact details
University Department of Anaesthetics
Royal Hallamshire Hospital
Glossop Road
Sheffield
S10 2JF
United Kingdom
+44 (0)114 271 1900 Ext 2102
m.w.reed@sheffield.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
RBF 96XX9; N0497017886
Study information
Scientific title
Acronym
Study hypothesis
Aims of the project: Prior determination of the optimum light and AminoLaevulinic Acid (ALA) parameters are a prerequisite for designing a successful treatment strategy, optimising the efficacy of ALA-induced PhotoDynamic Therapy (PDT) in the treatment of bladder cancer.
The objectives of this proposal are therefore to:
1. Determine the optimal dose of ALA and the time required for maximal photosensitisation in bladder tumours
2. Perform in-vivo light dosimetry studies to achieve the optimal depth of PDT in bladder tumours
3. Determine the dosing parameters and methodology for a clinical trial of PDT for the treatment of early superficial bladder cancer and carcinoma in-situ in patients who have failed to respond to conventional treatment and are faced with the prospect of cystectomy.
Ultimately, if the treatment proves successful, PDT may become the primary treatment modality for Carcinoma In Situ (CIS) and superficial bladder cancer. Although it will not be possible to undertake a clinical trial as part of this project it is hoped that it will be carried out subsequently using the data and expertise gained during this project.
Ethics approval
No ethics information provided at time of registration
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Cancer (neoplasms): Bladder (superficial)
Intervention
Patients will be accommodated in a side room with subdued light to minimise the risk of skin photosensitisation. Liver function tests will be performed 1 hour pre- and 24 hours post-operatively as there is a reported incidence of mild liver function test derangement following ALA administration.
Patients will be randomised to one of seven groups:
Group one: Control
Group two: Intra-Bladder (IB) instillation 3% ALA solution one hour pre-operatively
Group three: IB instillation 3% ALA solution four hours pre-operatively
Group four: IB instillation 10% ALA solution one hour pre-operatively
Group five: IB instillation 10% ALA solution four hours pre-operatively
Group six: Oral administration 30 mg/kg ALA four hours pre-operatively
Group seven: Oral administration 60 mg/kg ALA four hours pre-operatively
ALA Dosing:
Patients randomised to groups two to five will be catheterised one or four hours preoperatively and 50 ml of sterile 3% or 10% ALA solution will be instilled and the catheter clamped. Patients in groups six and seven will receive an oral dose of 30 or 60 mg/kg of ALA four hours pre-operatively. The oral dose has been chosen from previously published data.
Processing of tissue samples:
The time of removal of the resection specimen and histological assessment will be performed in the normal manner. Further small samples will be taken for Protoporphyrin IX (PpIX) analysis by fluorescence microscopy and High Performance Liquid Chromatography (HPLC). Further samples will micro-dissected into the different tissue components (namely mucosa, muscularis propria and tumour) and specific analysis of the level of PpIX in these components will be determined by Spectrophotometry (lS). Fluorescence microscopy will show the detailed microscopic distribution of the PpIX but is only a semi-quantitative technique, HPLC will determine the relative amounts of PpIX and profiles of other fluorescent porphyrins produced in the haem biosynthetic pathway and spectrophotometric analysis will give precise quantitative data on the level of PpIX in the different tissue components.
Light dosimetry:
Light dosimetry studies will be performed. Patient enrolment will be as described above, with patients about to undergo cystectomy being invited to participate in the study. 48 hours before surgery, patients will be given an appropriate dose of ALA (the time to light activation, dose and route of administration as determined in the phase 1 study). They will undergo flexible cystoscopy and the area of abnormality will be identified and biopsied. The bladder will then be distended with 100 ml sterile water.
Light will be delivered at 514 nm (n = 4), or 630 nm (n = 4) at two doses, (100 and 200 J/cm^2) to adjacent areas of tumour and normal tissue in each patient. The treated area will be marked with indict ink. At surgery 48 hours later, the appropriate sections of the bladder will be assessed histologically for mucosal denudation, extent and depth of necrosis and inflammatory response in the treated area.
Intervention type
Drug
Phase
Not Specified
Drug names
Aminolaevulinic acid
Primary outcome measures
Potential patient and health service benefits
Secondary outcome measures
Not provided at time of registration
Overall trial start date
01/07/1996
Overall trial end date
30/06/1997
Reason abandoned
Lack of resources
Eligibility
Participant inclusion criteria
28 patients with carcinoma in situ and superficial invasive carcinoma of the bladder who have been advised to have cystectomy or TransUrethral Resection of Tumour (TURT) (respectively) will be invited to participate in the study and written informed consent obtained.
Participant type
Patient
Age group
Adult
Gender
Not Specified
Target number of participants
28
Participant exclusion criteria
Not provided at time of registration
Recruitment start date
01/07/1996
Recruitment end date
30/06/1997
Locations
Countries of recruitment
United Kingdom
Trial participating centre
University Department of Anaesthetics
Sheffield
S10 2JF
United Kingdom
Sponsor information
Organisation
NHS R&D Regional Programme Register - Department of Health (UK)
Sponsor details
The Department of Health
Richmond House
79 Whitehall
London
SW1A 2NL
United Kingdom
+44 (0)20 7307 2622
dhmail@doh.gsi.org.uk
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
NHS Executive Trent (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary