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

Combination chemotherapy versus Bacillus Calmette-Guérin (BCG) for high-risk non-muscle invasive bladder cancer– a phase III multi-centre randomised controlled trial (COBRA)

Status

Recruiting

Phases

Phase 3

Study type

Interventional

Source

ISRCTN

Registry ID

ISRCTN92816346

Enrollment

520

Registered

2025-07-31

Start date

2025-08-01

Completion date

Unknown

Last updated

2026-08-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

High-risk non-muscle invasive bladder cancer Cancer

Interventions

Patients will receive up to four treatments in different sequences. Randomisation process: Sequential randomisation by computer-generated random permuted blocks. Treatment 1: BCG bladder instillation

Eligibility

Sex/Gender

All

Age

18 Years to 100 Years

Inclusion criteria

Inclusion criteria: 1. Written informed consent prior to any study-specific procedures 2. Age >=18 years 3. WHO performance status 0-3 4. A new diagnosis of high-risk urothelial NMIBC with no variant histology: 4.1. pT1 G2-3/high grade tumour (with or without CIS) OR 4.2. pTa G3/high grade tumours (with or without CIS) OR 4.3. Isolated carcinoma in situ (CIS) 5. Complete papillary tumour removal (apart from residual CIS) via TURBT 6. All patients with pT1 at initial TURBT should have had re-TURBT if there was no muscle in initial TURBT specimens. Re-resection should also be considered for patients with HG Ta if no muscle was present or for patients with HG T1 with muscle present at initial TURBT, according to local practice 7. Willing to use an effective method of contraception 8. Willing and able to comply with the follow-up schedule

Exclusion criteria

Exclusion criteria: 1. Any previous history of urothelial cancer 2. History of pure non-urothelial cell bladder cancer (adenocarcinoma, squamous cell carcinoma) 3. Evidence of neuroendocrine (small/ large cell) sarcomatoid, micropapillary or plasmacytoid variant urothelial cell cancer 4. Any urethral involvement 5. Any medical condition that contraindicates study treatment, including any known allergy to gemcitabine, docetaxel or BCG 6. Known pregnancy and/or currently breastfeeding 7. Known HIV, Hepatitis B or C with detectable viral load within 30 days prior to randomisation 8. Ongoing immunosuppressive medication, including steroids (>10 mg/day) - people receiving short courses (two weeks maximum) of steroids due to be discontinued prior to randomisation or using inhaled and topical steroids are eligible for randomisation 9. Active or treated malignancy within 1 year of randomisation (not including non-melanomatous skin carcinoma, NICE low-risk prostate cancer (T1/T2a, Gleason 6 PSA <10), in situ carcinoma of any site)

Design outcomes

Primary

Measure	Time frame
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.	—

Measure

Time frame

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.

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Secondary

Measure	Time frame
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, p	—

Measure

Time frame

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, p

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Countries

England, United Kingdom

Contacts

Public ContactSteven Penegar

cobra-icrctsu@icr.ac.uk+44 20 87224238

Outcome results

None listed

Source: ISRCTN (via WHO ICTRP) · Data processed: Aug 25, 2026