Intravesical Ialuril® plus oral combination of curcumine, quercetine, hyluronic acid (HA) and chondroitin sulphate (CS) for prophylaxis of recurrent non-muscle invasive transitional cell carcinoma (TCC) of the bladder

ISRCTN	ISRCTN45836359
DOI	https://doi.org/10.1186/ISRCTN45836359
Secondary identifying numbers	001/Ialuril_Oral

Submission date: 10/03/2013
Registration date: 20/03/2013
Last edited: 21/01/2019

Recruitment status: Stopped
Overall study status: Stopped
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Transitional cell carcinoma (TCC) of the bladder is one of the most common cancers. In 75-85% of patients the cancer is contained inside the lining of the bladder (non-muscle-invasive bladder cancer). A surgical technique called complete transurethral resection of visible tumour (TURBT) is the gold standard treatment for non-invasive bladder tumours. A single dose of chemotherapy, usually mitomycin C, is delivered directly into the bladder using a catheter (intravesical therapy) to destroy any remaining microscopic tumour and prevent the cancer from coming back. Intravesical therapy is also used in a maintenance (long term) fashion to prolong the beneficial effects of the chemotherapy. Although immediate intravesical mitomycin C or epirubicin is highly recommended, it should not be used in patients with a bladder perforation as a small number of serious complications related to mitomycin C extravasation (leakage) have been reported. The bladder lining (urothelium) prevents undesirable substances penetrating the deeper layers of the bladder wall and neutralises toxic substances. Glycosaminoglycans (GAGs) make the inner bladder wall impervious to the contents of the urine. Two key components of the layer are hyaluronic acid (HA) and chondroitin sulphate (CS). The aim of this study is to find out whether intravesical HA and CS (Ialuril®) followed by oral HA and CS plus curcumine and quercetine are safe and effective at preventing the recurrence of TCC after TURBT.

Who can participate?
Patients aged over 18 with TCC

What does the study involve?
Patients receive intravesical HA and CS (Ialuril®) immediately after TURBT, followed by oral treatment with pills (one a day for 90 days) containing CS, HA, quercitine and curcumine. TCC recurrence is assessed using ultrasound, urine tests and endoscopic assessment after 3 months.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
Institut Biochimique SA (IBSA) (Italy)

When is the study starting and how long is it expected to run for?
January 2012 to December 2013

Who is funding the study?
Institut Biochimique SA (IBSA) (Italy)

Who is the main contact?
Dr Massimo Lazzeri

Contact information

Dr Massimo Lazzeri
Scientific

via Stamira d'Ancona 20
Milan
20127
Italy

Study information

Study design	Prospective longitudinal investigative pilot non-randomised (phase 1b) study
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 to request a patient information sheet
Scientific title	Intravesical Ialuril® plus oral combination of curcumine, quercetine, hyluronic acid (HA) and chondroitin sulphate (CS) for prophylaxis of recurrent non-muscle invasive transitional cell carcinoma (TCC) of the bladder: a prospective longitudinal investigative pilot non-randomised study
Study objectives	To test the hypothesis whether or not immediate post-TURBT intravesical instillation of a combination of HA and CS (Ialuril®) repairing coating - followed by oral administration of a combination of HA and CS plus curcumine and quercetine maintaining coating - is safe, tolerated and effective in preventing the recurrence of TCC after TURBT in patients with superficial low-intermediate risk pTa-1 TCC.
Ethics approval(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	Superficial (non muscle invasive) transitional cell carcinoma
Intervention	All the patients underwent standard transurethral resection of the visible lesions. Immediate post-TURBT intravesical instillation of a combination of HA and CS (Ialuril®: 50 ml/vial solution containing HA 800 mg and CS 1 mg) followed by oral treatment with pills (one a day for 90 days) containing CS 200 mg, HA 20 mg, quercitine 200 mg and curcumine 100 mg.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase I
Drug / device / biological / vaccine name(s)	Laluril®
Primary outcome measure	1. Tolerability, reported as discontinuation or deviation of the protocol and safety as general or local side effects 2. Efficacy, defined as the absence of recurrence as defined by negative ultrasound evaluation, negative urine cytology and negative endoscopic assessment after 3 months
Secondary outcome measures	Morphological immunohistochemical assessment, comparing samples at entry and after 3 months for transient receptor protein vanilloids 1 (TRPV1) expression and GAGs
Overall study start date	01/01/2012
Completion date	31/12/2013
Reason abandoned (if study stopped)	Local ethical committees requested several changes

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	20
Key inclusion criteria	Patients (male and female) with single, ultrasound detected < 3 cm tumor diameter, or multiple 3 or less, each < 1 cm, low- and intermediate-grade (Grade II in old nomenclature) superficial TCC at the first diagnosis, confirmed by flexible cystoscopy and cold cup biopsy
Key exclusion criteria	1. Concomitant CIS 2. Involvement of the prostatic urethra 3. Neurogenic bladder 4. Diabetes mellitus type I and II 5. Previous bladder or prostate surgery (any kind) 6. Previous treatment with drugs (capsaicin, vanilloids, ovanil, botulinum toxin etc) 7. Further exclusion criteria were previous chemotherapies and/or pelvic radiotherapy
Date of first enrolment	01/01/2012
Date of final enrolment	31/12/2013

Locations

Countries of recruitment

Italy

Study participating centre

via Stamira d'Ancona 20

Milan
20127
Italy

Sponsor information

Institut Biochimique SA (IBSA) (Italy)
Industry

Via Emilia
Lodi
26900
Italy

Website	http://www.ibsa-international.com/
"ROR"	https://ror.org/02cf8gj49

Funders

Funder type

Industry

Institut Biochimique SA (IBSA) (Italy)

No information available

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

Editorial Notes

21/01/2019: Study abandoned due to several changes requested by local ethical committees
19/04/2017: Plain English summary added.