Durvalumab+ Gemcitabine/Cisplatin (Neoadjuvant Treatment) and Durvalumab (Adjuvant Treatment) in Patients With MIBC

Study Overview
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Brief Summary
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A Global Study to Determine the Efficacy and Safety of Durvalumab in Combination with Gemcitabine+Cisplatin for Neoadjuvant Treatment and Durvalumab Alone for Adjuvant Treatment in Patients with Muscle-Invasive Bladder Cancer

Official Title
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A Phase III, Randomized, Open-Label, Multi-Center, Global Study to Determine the Efficacy and Safety of Durvalumab in Combination With Gemcitabine+Cisplatin for Neoadjuvant Treatment Followed by Durvalumab Alone for Adjuvant Treatment in Patients With Muscle-Invasive Bladder Cancer.

Conditions
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Muscle Invasive Bladder Cancer

Intervention / Treatment
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* Drug: Durvalumab
* Drug: Cisplatin
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion: Patient resectable muscle-invasive bladder cancer with clinical stage T2-T4aN0/1M0 with transitional and mixed transitional cell histology Patients must be planning to undergo a radical cystectomy Patients who have not received prior systemic chemotherapy or immunotherapy for treatment of MIBC ECOG performance status of 0 or 1 Must have a life expectancy of at least 12 weeks at randomization Exclusion: Evidence of lymph node (N2-N3) or metastatic (M1) disease at time of screening. Prior pelvic radiotherapy treatment within 2 years of randomization to study Prior exposure to immune-mediated therapy (with exclusion of Bacillus-Calmette Guerin [BCG]), including but not limited to other anti-CTLA-4, anti-PD-1, anti PD-L1, or anti-PD-L2 antibodies. Current or prior use of immunosuppressive medication within 14 days before the first dose of investigational product (IP). The following are exceptions to this criterion: Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection); Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent; Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication) Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Uncontrolled intercurrent illness Active infection including Tuberculosis, Hepatitis B, Hepatitis C, and Human Immunodeficiency

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Chemotherapy + Durvalumab | Drug: Durvalumab<br>* Anti- PD-L1 Antibody<br>Drug: Cisplatin<br>* Chemotherapy Agent<br>Drug: Gemcitabine<br>* Chemotherapy agent<br>|
| Active Comparator: Arm 2<br>Chemotherapy alone | Drug: Cisplatin<br>* Chemotherapy Agent<br>Drug: Gemcitabine<br>* Chemotherapy agent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic complete response (pCR) rates at time of cystectomy |  | Up to 6 months | 
| Event-free survival (EFS) per central review defined as time from randomization to event |  | Up to 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who achieve <P2 at time of cystectomy |  | Up to 6 months | 
| EFS at 24 months (EFS24) defined as time from randomization to event |  | Up to 24 months | 
| Proportion of patients who undergo cystectomy |  | Up to 6 months | 
| Overall survival rate at 5 years |  | Up to 60 months | 
| PFS2 defined as time from randomization to event following subsequent therapy |  | Up to 84 months | 
| Safety and Tolerability as evaluated by adverse events occurring throughout the study |  | Up to 84 months | 
| Immunogenicity of durvalumab when used in combination with gemcitabine/cisplatin as measured by presence of antidrug antibodies (ADA) |  | Up to 12 months | 
| Overall Survival |  | Up to 84 months | 
| Metastasis-free survival per investigator assessment or local biopsy review. |  | Up to 48 months | 
| Disease-specific survival per investigator assessment or local biopsy review. |  | up to 48 months | 
| Disease-free survival |  | Up to 48 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bladder Cancer, Immunotherapy, PD-L1, Durvalumab (MEDI4736)