| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Non-muscle Invasive Transitional cell Carcinoma of the Bladder | |
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10005004 | | E.1.2 | Term | Bladder cancer NOS | | E.1.2 | System Organ Class | 100000004864 | |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | 1.To determine if the addition of the oral COX-2 inhibitor celecoxib to standard therapy is more effective in terms of disease recurrence at 3 years than standard therapy alone for the treatment of superficial TCC of the bladder at high risk of recurrence.
2.To determine if the addition of the oral COX-2 inhibitor celecoxib to standard therapy is more effective in terms of disease recurrence at 3 years than standard therapy alone for the treatment of superficial TCC of the bladder at intermediate risk of recurrence. | |
| E.2.2 | Secondary objectives of the trial | 1.To determine if the combination of celecoxib plus standard therapy is more effective than standard therapy in terms of progression to invasive disease (high risk patients), recurrence rate, disease-free survival and overall survival.
2.To determine the safety and tolerability of celecoxib in this patient population.
3.To determine whether celecoxib reduces the inflammatory side effects of BCG and MMC and improves quality of life (QL) of patients treated with BCG or MMC.
4.To determine the cost effectiveness of celecoxib in combination with standard therapy for superficial bladder cancer.
5.To compare the reduction in recurrence within the first two years with that observed beyond two years, an exploratory analysis to see whether there is any evidence treatment is only effective whilst it is being given.
| |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | 1.Primary or recurrent superficial TCC of the bladder of intermediate or high risk of recurrence.
2.Age > 18
3.WHO performance status 0, 1 or 2
4.No evidence of upper tract TCC on imaging studies within the past 36 months or before randomisation
5.Pre-treatment haematology and biochemistry values within acceptable limits.6.Negative pregnancy test for women of child-bearing potential
7.At least 2 months since prior celecoxib or NSAIDs (other than low dose aspirin (<=150mg daily)
8.Baseline ECG showing no evidence of established or acute ischaemic heart disease and normal clinical cardiovascular assessment
9.Written informed consent and available for long-term follow-up
| |
| E.4 | Principal exclusion criteria | 1.Low risk of recurrence TCC of the bladder
2.Carcinoma involving the prostatic urethra or upper urinary tract
3.>=T2 TCC or previous history of>=T2
4.Significant bleeding disorder
5.Chronic or acute renal disorder
6.Oesophageal gastric, pyloric channel, or duodenal ulceration diagnosed or treated within the past 30 days
7.Active or previous peptic ulceration or gastrointestinal bleeding in the last year
8.Inflammatory bowel disease (e.g. Crohn’s disease or ulcerative colitis)
9.Pancreatitis
10.Pregnant or lactating women or patients of childbearing potential unwilling or unable to use adequate non-hormonal contraception.
11.Hypersensitivity or adverse reactions to sulfonamides, COX-2 inhibitors, salicylates, or other NSAIDs
12.On current or planned chronic NSAIDs therapy (except low dose aspirin <= 150 mg once daily). Chronic use of NSAIDs is defined as a frequency of 1 or more a day, for more than 50 consectutive days in a year.
13.Regular use of low-dose celecoxib within the previous 8 weeks.
14.Current or long-term use of corticosteroids
15.Known or suspected congestive heart failure (>NYHA I) and/or coronary heart disease, previous history of myocardial infarction, coronary artery bypass graft, invasive coronary revascularization or angina, uncontrolled arterial hypertension (ie BP >180/110mmHg under treatment with two anti-hypertensive drugs), rhythm abnormalities requiring permanent treatment. ECG should be within limits prior to starting trial therapy.
16.Patients with diabetes controlled by diet and oral medication are eligible for the study; however patients treated with insulin will be excluded.
17.Past history of stroke/TIA, symptomatic peripheral vascular disease.
18.Other malignancy within the past 5 years, except: non-melanomatous skin cancer cured by excision, adequately treated carcinoma in situ of the cervix or DCIS/LCIS of the breast.
19.Concurrent chemotherapy other than intravesical MMC
20.Psychiatric or addictive disorders which could preclude obtaining informed consent.
| |
| E.5 End points |
| E.5.1 | Primary end point(s) | | Time to recurrence of TCC of the bladder. The time point of interest is 3 years. | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 | The trial involves single site in the Member State concerned | No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | | The study end date is deemed to be the date of the last data capture. | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | |
