BCG + MMC: Adding Mitomycin C to BCG in High-risk, Non-muscle-invasive Bladder Cancer

Inclusion Criteria:

1. Males or females with confirmed high grade pTa or stage pT1 (any grade) non-muscleinvasive bladder cancer on initial or re-resection histology (concurrent carcinomain situ is allowed).

2. Age ≥ 18 yrs

3. No macroscopically visible disease at cystoscopy within 8 weeks prior torandomisation. This may either be the initial TURBT at which the primary tumour wascompletely 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 confirmed by pre-randomisation bloodtests.

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 ofliteracy, insufficient English or limited vision

8. Willing and able to comply with all study requirements, including treatment, timingand/or nature of all required assessments

9. Signed, written informed consent

Exclusion Criteria:

1. Contraindications or hypersensitivity to investigational products, BCG and MM

2. Prior treatment with any other intravesical agent including BCG or MM (excludessingle 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 thebladder

5. Bladder dysfunction precluding intravesical therapy e.g. Severe urinary incontinenceor 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) orimmunosuppressive therapy (e.g. corticosteroids), or cancer therapy (cytotoxicdrugs, radiation)

8. Prior radiotherapy of the pelvis

9. Prior or current treatment with radiotherapy-response or biological-responsemodifiers

10. Clinical evidence of existing active tuberculosis

11. History of another malignancy within 5 years prior to registration. Patients withnon-melanomatous carcinoma of the skin are eligible for this study.

12. Serious medical or psychiatric conditions that might limit the ability of thepatient 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 potentialmust have a negative pregnancy test done within 7 days prior to registration. Menmust have been surgically sterilised or use a (double if required) barrier method ofcontraception.