A Study Of Avelumab In Patients With Locally Advanced Or Metastatic Urothelial Cancer (JAVELIN Bladder 100)
Condition: Urothelial Cancer
Intervention: Avelumab; Best Supportive Care; Following the planned interim analysis for this study: Avelumab
Intervention description: 1 hour intravenous infusion every 2 weeks (Q2W) in 4 week cycles; BSC will be administered as deemed appropriate by the treating physician, and could include treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management (including palliative radiotherapy), etc. BSC does not include any active anti-tumor therapy, however local radiotherapy of isolated lesions with palliative intent is acceptable.; 1 hour intravenous infusion every 2 weeks (Q2W) in 4 week cycles
Intervention MeSH terms: Avelumab; Antibodies, Monoclonal
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 700.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Bladder cancer; Urologic neoplasms; urothelial carcinoma; PD-L1; programmed cell death protein; maintenance treatment

Summary:

      The main purpose of this study is to compare maintenance treatment with avelumab plus best
      supportive care (BSC) with BSC alone, to determine if avelumab has an effect on survival in
      patients with locally advanced or metastatic urothelial cancer that did not worsen during or
      following completion of first-line chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed, unresectable locally advanced or metastatic transitional
             cell carcinoma of the urothelium

          -  Stage IV disease at the start of first-line chemotherapy

          -  Measurable disease (per RECIST v1.1) prior to the start of first-line chemotherapy

          -  Prior first-line chemotherapy must have consisted of at least 4 cycles and no more
             than 6 cycles of gemcitabine + cisplatin and/or gemcitabine + carboplatin

          -  No evidence of progressive disease following completion of first-line chemotherapy
             (i.e., ongoing CR, PR, or SD per RECIST v1.1 guidelines )

        Exclusion Criteria:

          -  Prior adjuvant or neoadjuvant systemic therapy within 12 months of randomization

          -  Prior immunotherapy with IL-2, IFN-α, or an anti-PD-1, anti-PD-L1, anti-PD-L2,
             anti-CD137, or CTLA 4 antibody (including ipilimumab), or any other antibody or drug
             specifically targeting T-cell co-stimulation or immune checkpoint pathways

          -  Persisting toxicity related to prior therapy (Grade >1 NCI CTCAE v4.0); however,
             alopecia, sensory neuropathy (Grade 2 or less), or other (Grade 2 or less) adverse
             events not constituting a safety risk based on the investigator's judgement are
             acceptable.

          -  Patients with known symptomatic central nervous system (CNS) metastases requiring
             steroids

          -  Diagnosis of any other malignancy within 5 years prior to randomization, except for
             adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the
             breast or of the cervix, low grade prostate cancer on surveillance without any plans
             for treatment intervention, or prostate cancer that has been adequately treated with
             prostatectomy or radiotherapy and currently with no evidence of disease or symptoms.