E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
High grade non muscle invasive bladder cancer |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
To assess whether patients treated with a combination of BCG and MM have fewer recurrences and live longer than patients treated with BCG alone. |
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E.2.2 | Secondary objectives of the trial |
To compare: 1) Activity (clear cystoscopy at 3 months) 2) Time to recurrence 3) Time to progression (recurrence of higher grade or stage cancer) 4) Safety (adverse events) 5) Health-related quality of life (HRQL) 6) Overall survival time (death from any cause) 7) Feasibility (compliance with intravesical therapy) 8) Marginal resource use (e.g. number of GP visits, number of outpatient and emergency department visits, number of inpatient admissions and the number of days admitted) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males or females with confirmed high grade pTa or stage pT1 (any grade) non-muscle invasive bladder cancer on initial or re-resection histology (concurrent carcinoma in situ is allowed). 2. Age ≥ 18 yrs 3. No macroscopically visible disease at cystoscopy within 8 weeks prior to randomisation. This may either be the initial TURBT at which the primary tumour was completely resected, or a planned second cystoscopy and/ or re-resection done within 8 weeks of the initial TURBT. 4. ECOG Performance Status of 0-2 5. Adequate bone marrow, renal and liver function 6. Study treatment both planned and able to start within 4 weeks of randomisation 7. Is willing to complete HRQL questionnaires or is unable to complete them because of literacy, insufficient English or limited vision 8. Willing and able to comply with all study requirements, including treatment, timing and/or nature of all required assessments 9. Signed, written informed consent |
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E.4 | Principal exclusion criteria |
1. Contraindications or hypersensitivity to investigational products, BCG and MM 2. Prior treatment with any other intravesical agent including BCG or MM (excludes single doses given post TURBT) 3. Current or past transitional cell carcinoma (TCC) of the upper urinary tract 4. Prior muscle-invasive (stage T2 or higher) transitional-cell carcinoma of the bladder 5. Bladder dysfunction precluding intravesical therapy e.g. Severe urinary incontinence or overactive or spastic bladder 6. Life expectancy < 3 months 7. Congenital or acquired immune deficiencies, whether due to a concurrent disease (e.g. acquired immune deficiency syndrome (AIDS), leukaemia, lymphoma) or immunosuppressive therapy (e.g. corticosteroids), or cancer therapy (cytotoxic drugs, radiation) 8. Prior radiotherapy of the pelvis 9. Prior or current treatment with radiotherapy-response or biological-response modifiers 10. Clinical evidence of existing active tuberculosis 11. History of another malignancy within 5 years prior to registration. Patients with non-melanomatous carcinoma of the skin are eligible for this study. 12. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol. 13. Pregnancy, lactation, or inadequate contraception. Women must be post menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilised or use a (double if required) barrier method of contraception |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Evaluation timepoints of thus end point would be at time of identification of recurrent bladder cancer, time of death (if occurs) |
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E.5.2 | Secondary end point(s) |
1) Activity (clear cystoscopy at 3 months) 2) Time to recurrence 3) Time to progression (recurrence of higher grade or stage cancer) 4) Safety (adverse events) 5) Health-related quality of life (HRQL) 6) Overall survival time (death from any cause) 7) Feasibility (compliance with intravesical therapy) 8) Marginal resource use (e.g. number of GP visits, number of outpatient and emergency department visits, number of inpatient admissions and the number of days admitted) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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 | No |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
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
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Database locked for analysis. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 10 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |