Non-muscle-invasive Bladder Cancer
Conditions
Keywords
Durvalumab, BCG, MEDI4736, NMIBC, PD-L1, DFS, OS
Brief summary
This is a randomized, open-label, multi-center, global, phase III study to determine the efficacy and safety of Durvalumab + BCG combination therapy in the treatment of patients with non-muscle-invasive bladder cancer
Detailed description
Patients will be randomized in a 1:1:1 ratio to receive treatment with Durvalumab + BCG combination therapies, or Standard of Care (SoC) therapy.
Interventions
BIOLOGICALDurvalumab (MEDI4736)
Investigational product
BIOLOGICALBacillus Calmette-Guerin (BCG)
Standard of care
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
For inclusion in the study, patients should fulfill the following criteria: * Aged at least 18 years * BCG-naïve (patients who have not received prior intravesical BCG or who previously received but stopped BCG more than 3 years before study entry are eligible) * Local histological confirmation (based on pathology report) of high-risk transitional cell carcinoma of the urothelium of the urinary bladder confined to the mucosa or submucosa. A high risk tumor is defined as one of the following * T1 tumor * High grade/ G3 tumor * CIS * Multiple and recurrent and large (with diameter of largest tumor ≥3 cm) tumors (all conditions must be met in this point) * Complete resection of all Ta/T1 papillary disease prior to randomization, with the TURBT removing high-risk NMIBC performed not more than 4 months before randomization in the study. Patients with residual CIS after TURBT are eligible * No prior radiotherapy for bladder cancer * No prior exposure to immune-mediated therapy of cancer including, but not limited to, other anti CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 antibodies. Patients who have been treated with anticancer vaccines will be excluded
Exclusion criteria
Patients should not enter the study if any of the following
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The efficacy of Durvalumab + BCG (induction plus maintenance) combination therapy compared to SoC in terms of Disease free survival (DFS) in patients with NMIBC | Up to 4 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The efficacy of Durvalumab + BCG (induction plus maintenance) therapy compare to SoC in terms of DFS after 24 months of last subject's last dose of IP | Up to 4 years | — |
| Disease-related symptoms and HRQoL in patients with NMIBC treated with Durvalumab + BCG combination therapies compared to SoC and compared to each other using the EORTC QLQ-C30 questionnaire | Up to 4 years | EORTC QLQ-C30 measures cancer patients' functioning (HRQoL) and symptoms for all cancer types and consists of functional, symptom and a global measure of health status scales |
| Patient-reported treatment tolerability using specific PRO CTCAE symptoms | Up to 4 years | — |
| The serum concentration of Durvalumab plus BCG combination therapies | Up to 4 years | — |
| The immunogenicity of Durvalumab when used in combination with BCG treatment assessed by descriptive summary of presence of ADAs | Up to 4 years | Serum will be tested for the presence of anti-drug antibodies. |
| The efficacy of Durvalumab + BCG (induction plus maintenance) therapy compare to SoC in terms of OS | Up to 7 years | — |
| The efficacy of Durvalumab + BCG (induction plus maintenance) combination therapy compared to SoC in terms of time to muscle invasive bladder cancer and/or metastatic disease | Up to 7 years | — |
| The efficacy of Durvalumab + BCG combination therapies compared to each other in terms of DFS after 24 months of last subject's last dose of IP | Up to 4 years | — |
| The efficacy of Durvalumab + BCG (induction only) combination therapy compared to SoC in terms of OS | Up to 7 years | — |
| The efficacy of Durvalumab + BCG combination therapies compared to each other in terms of OS | Up to 7 years | — |
| The efficacy of Durvalumab + BCG (induction only) combination therapy compared to SoC in terms of time to muscle invasive bladder cancer and/or metastatic disease | Up to 7 years | — |
| The efficacy of Durvalumab + BCG combination therapies compared to each other in terms of time to muscle invasive bladder cancer and/or metastatic disease | Up to 7 years | — |
| Disease-related symptoms and HRQoL in patients with NMIBC treated with Durvalumab + BCG combination therapies compared to SoC and compared to each other using the the EORTC QLQ NMIBC24 questionnaire | Up to 4 years | EORTC QLQ-NMIBC24 assesses disease-specific symptoms of patients with intermediate to high-risk NMIBC. |
| The efficacy of durvalumab + BCG combination therapy compared to SoC in terms of CRR for patients with CIS prior to study entry or at baseline cystoscopy | Up to 4 years | CRR at 6 months in patients with CIS prior to the study entry or at baseline cystoscopy |
| The efficacy of Durvalumab + BCG (induction only) combination therapy compared to SoC in terms of DFS after 24 months of last subject's last dose of IP | Up to 4 years | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of treatment-related adverse events as assessed by CTCAE v4.0 in patients receiving Durvalumab + BCG combination therapies compared to SoC | Up to 4 years | The safety and tolerability profile of Durvalumab + BCG combination therapies compared to SoC using vital signs, laboratory data, electrocardiograms (ECGs), and adverse event data. |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Japan, Netherlands, Poland, Russia, Spain, United Kingdom
Outcome results
None listed