Adult patients (age =18 years) with histologically or cytologically documented transitional cell carcinoma (transitional cell and mixed transitional/non transitional cell histologies) of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra), unresectable Stage IV (ie, =T4bN0M0 for bladder), and who are chemotherapy-naïve. MedDRA version: 20.0 Level: LLT Classification code 10022880 Term: Invasive bladder c
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1, Patients with histologically or cytologically documented, unresectable, Stage IV transitional cell carcinoma of the urothelium who have not been previously treated with first-line chemotherapy. 2, Patients eligible or ineligible for cisplatin-based chemotherapy. Cisplatin ineligibility is defined as meeting 1 of the following criteria: • Creatinine clearance =65 years) yes F.1.3.1 Number of subjects for this age range 365
Exclusion criteria
Exclusion criteria: 1, Prior exposure to immune-mediated therapy, including but not limited to, other anti CTLA 4, anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies, including therapeutic anticancer vaccines. Prior local intervesical chemotherapy or immunotherapy is allowed if completed at least 28 days prior to the initiation of study treatment.2, History of allogenic organ transplantation that requires use of immunosuppressive agents. 3, Active or prior documented autoimmune or inflammatory disorders. The following are exceptions to this criterion: • Patients with vitiligo or alopecia • Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement •Any chronic skin condition that does not require systemic therapy •Patients w/o active disease in the last 3 years may be included but only after prior consultation w/ AstraZeneca •Patients w/ celiac disease controlled by diet alone may be included but only after prior consultation w/ AstraZeneca but only after prior consultation w/ AstraZeneca. 4, Brain metastases or spinal cord compression unless the patient's condition is stable and off steroids for at least 14 days prior to the start of study treatment. Patients with suspected or known brain metastases at screening should have an MRI(preferred)/CT, preferably with IV contrast to access baseline disease status. 5, Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV). 6, Current or prior use of immunosuppressive medication within 14 days before the first dose of MEDI4736 or tremelimumab. 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). 7, Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of IP.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To assess the efficacy of MEDI4736 + tremelimumab combination therapy versus SoC in terms of OS in patients with unresectable Stage IV UC; 2. To assess the efficacy of MEDI4736 monotherapy versus SoC in terms of OS in patients with unresectable Stage IV PD L1 High UC ; Secondary Objective: 1. To assess the efficacy of MEDI4736 +tremelimumab combination therapy versus SoC in terms of PFS in patients with UC. 2. To assess the efficacy of MEDI4736 monotherapy compared to SoC in terms of PFS in patients with PD-L1-High UC 3. To further assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of ORR. 4. To further assess the efficacy of MEDI4736 monotherapy compared to SoC in terms of ORR 5. To assess disease-related symptoms and HRQoL in UC patients treated with MEDI4736 monotherapy and MEDI4736 + tremelimumab combination therapy compared with SoC and each other using the FACTBL questionnaire. 6. To assess the PK of MEDI4736 monotherapy and MEDI4736 + tremelimumab combination therapy. 7. To investigate the immunogenicity of MEDI4736 monotherapy and MEDI4736 + tremelimumab combination therapy 8. To assess the efficacy profile of MEDI4736 monotherapy in patients who are not cisplatin-eligible ;Primary end point(s): Overall survival (OS);Timepoint(s) of evaluation of this end point: Up to 4 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1, Progression-free survival (PFS) 2, OS24. 3, Proportion of patients alive and progression-free at 12 months. 4, Objective response rate. 5, Duration of response. 6, Disease control rate. 7, Best objective response.;Timepoint(s) of evaluation of this end point: Baseline to the end of treatment | — |
Countries
Australia, Austria, Belgium, Brazil, Canada, Chile, Denmark, France, Germany, Greece, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Portugal, Russian Federation, Spain, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Trial Transparency
AstraZeneca AB
Outcome results
None listed