A Study of Atezolizumab Compared With Chemotherapy in Participants With Locally Advanced or Metastatic Urothelial Bladder Cancer [IMvigor211]
Condition: Bladder Cancer
MeSH terms: Urinary Bladder Neoplasms
Intervention: Atezolizumab (MPDL3280A) [TECENTRIQ], an engineered anti-PDL1 antibody; Docetaxel; Paclitaxel; Vinflunine
Intervention description: Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on Day 1 of each 21-day cycle.; Docetaxel 75 mg/m^2 will be administered intravenously on Day 1 of each 21-day cycle.; Paclitaxel 175 mg/m^2 will be administered intravenously on Day 1 of each 21-day cycle.; Vinflunine 320 mg/m^2 will be administered intravenously on Day 1 of each 21-day cycle.
Intervention MeSH terms: Paclitaxel; Docetaxel; Atezolizumab; Antibodies
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 931.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a Phase III, global, multicenter, open-label, two-arm, randomized, controlled study
      designed to evaluate the efficacy and safety of atezolizumab compared with chemotherapy in
      participants with locally advanced or metastatic urothelial bladder cancer (UBC) who have
      progressed during or following a platinum-containing regimen. The anticipated time on study
      treatment is based on continued clinical benefit, i.e., until disease progression or
      unacceptable toxicity. The target sample size is 931 participants.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically documented locally advanced or metastatic UBC
             (including renal pelvis, ureters, urinary bladder, and urethra).

          -  Representative tumor specimens as specified by the protocol

          -  Disease progression during or following treatment with at least one
             platinum-containing regimen for inoperable, locally advanced or metastatic UBC or
             disease recurrence

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Life expectancy greater than or equal to (>/=) 12 weeks

          -  Measurable disease, as defined by RECIST v1.1

          -  Adequate hematologic and end organ function

          -  For women of childbearing potential, agreement to refrain from heterosexual
             intercourse or use contraceptive methods that result in a failure rate of < 1% per
             year during the treatment period and for at least 5 months after the last dose of
             atezolizumab, 3 months after the last dose of vinflunine and 6 months from the last
             dose of paclitaxel or docetaxel.

          -  For men, agreement to refrain from heterosexual intercourse or use contraceptive
             methods that result in a failure rate of < 1% per year during the treatment period and
             for at least 3 months after the last dose of vinflunine and 6 months from the last
             dose of paclitaxel or docetaxel, and agreement to refrain from donating sperm

        Exclusion Criteria:

          -  Any approved anti-cancer therapy within 3 weeks prior to initiation of study treatment

          -  Treatment with any other investigational agent or participation in another clinical
             trial with therapeutic intent within 28 days prior to enrollment

          -  Active or untreated central nervous system (CNS) metastases as determined by computed
             tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and
             prior radiographic assessments

          -  Leptomeningeal disease

          -  Malignancies other than UBC within 5 years prior to Cycle 1, Day 1, with the exception
             of those with a negligible risk of metastasis or death and treated with expected
             curative outcome, or localized prostate cancer treated with curative intent and
             absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer

          -  Pregnant and lactating women

          -  Significant cardiovascular disease

          -  Severe infections within 4 weeks prior to randomization

          -  Major surgical procedure other than for diagnosis within 4 weeks prior to
             randomization

          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to
             chimeric or humanized antibodies or fusion proteins; known hypersensitivity or allergy
             to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the
             atezolizumab formulation

          -  History of autoimmune disease

          -  Prior allogeneic stem cell or solid organ transplant

          -  History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
             pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening
             chest CT scan

          -  Positive test for human immunodeficiency virus (HIV) and/or active hepatitis B or
             hepatitis C or tuberculosis

          -  Administration of a live, attenuated vaccine within 4 weeks prior to randomization

          -  Prior treatment with cluster of differentiation 137 (CD137) agonists or immune
             checkpoint blockade therapies, including anti-cytotoxic T-lymphocyte-associated
             protein 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1) or anti-programmed
             death-ligand 1 (anti-PD-L1) therapeutic antibodies