Is Gem-Doce an alternative to BCG treatment for people with early bladder cancer?

Not yet submitted, ref: 25/SC/0262

High-grade recurrence-free survival (hgRFS), i.e. time to first identification of high-grade recurrent disease, stage progression, metastatic disease or death from any cause. The primary analysis of hgRFS is planned to take place once the target number of events has been observed, expected when participants have at least 2 years of follow-up and have completed study treatment.

Persistent/recurrent HG pT1 or HG Ta papillary bladder cancer following induction therapy or persistent carcinoma in situ at 6 months will be considered high-grade recurrence events. The development of nodal disease or distant metastatic disease (based on cross-sectional imaging or histological confirmation - where biopsy is done, histology results will supersede imaging) is considered a high-grade recurrence event.

1. Recurrence-free survival, defined in whole days as the time from the date of randomisation to the date of confirmed recurrence of non-muscle invasive bladder cancer (includes all events described in the primary endpoint, as well as recurrences of any grade); analysis after approximately 2 years follow-up (at the time of the primary endpoint).
2. Progression-free survival, defined in whole days as the time from the date of randomisation to the date of confirmed progression to muscle-invasive bladder cancer, nodal disease, distant metastatic disease, or death from any cause; analysis after approximately 2 years of follow-up (at the time of the primary endpoint)
3. Cystectomy-free survival, defined in whole days as the time from the date of randomisation to the date of cystectomy; analysis after approximately 2 years of follow-up (at the time of the primary endpoint)
4. Cancer-specific survival, defined in whole days as the time from the date of randomisation to the date of death specifically from bladder cancer; analysis after approximately 2 years of follow-up (at the time of the primary endpoint)
5. Overall survival, defined in whole days as the time from the date of randomisation to the date of death; for those who have not been reported as dead at the time of analysis; analysis after approximately 2 years of follow-up (at the time of the primary endpoint)
6. Complete response rate at 6 months (in patients with carcinoma in situ at baseline only), measured as the number of patients with an absence of cancer at 6-month cystoscopy (in patients with carcinoma in situ at baseline only)
7. Number of instillations received, measured over the 24-month induction and maintenance visit schedule of allocated treatment
8. Clinician assessed adverse events, measured by clinician-reported symptoms using CTCAE v5 over the 24-month induction and maintenance visit schedule
9. Patient-reported outcomes: health-related quality of life with an emphasis on overall quality of life, physical functioning, urinary symptoms and intravesical treatment issues, measured over the 24-month maintenance visit follow-up period, measured by the generic EORTC QLQ-F17, disease-specific QLQ-NMIBC24 and the generic EQ-5D-5L validated instruments
10. Costs to the NHS and personal social services, measured over the 24-month maintenance visit follow-up period and extrapolated over the patient lifetime
11. Incremental cost per quality-adjusted life year gained, measured over the 24-month maintenance visit follow-up period and extrapolated over the patient lifetime from responses to the EQ-5D-5L, cross-walked from responses to the EORTC QLQ-F17 as a sensitivity analysis

Unless advised otherwise by the IDMC, secondary endpoints will be reported at the time of the primary analysis.