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A Study of Atezolizumab Versus Observation as Adjuvant Therapy in Participants With High-Risk Muscle-Invasive Urothelial Carcinoma (UC) After Surgical Resection

NCT02450331

Description:

This Phase III, open-label, randomized, multicenter study is to evaluate the efficacy and safety of adjuvant treatment with atezolizumab compared with observation in participants with muscle-invasive UC who are at high risk for recurrence following resection. Eligible participants were randomized by a 1:1 ratio into atezolizumab group or control group.

Related Conditions:
  • Bladder Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Atezolizumab Versus Observation as Adjuvant Therapy in Participants With High-Risk Muscle-Invasive Urothelial Carcinoma (UC) After Surgical Resection
  • Official Title: A Phase III, Open-Label, Multicenter, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Versus Observation as Adjuvant Therapy in Patients With High-Risk Muscle-Invasive Urothelial Carcinoma After Surgical Resection

Clinical Trial IDs

  • ORG STUDY ID: WO29636
  • SECONDARY ID: 2014-005603-25
  • NCT ID: NCT02450331

Conditions

  • Carcinoma, Transitional Cell

Interventions

DrugSynonymsArms
AtezolizumabTECENTRIQ®; MPDL3280AAtezolizumab

Purpose

This Phase III, open-label, randomized, multicenter study is to evaluate the efficacy and safety of adjuvant treatment with atezolizumab compared with observation in participants with muscle-invasive UC who are at high risk for recurrence following resection. Eligible participants were randomized by a 1:1 ratio into atezolizumab group or control group.

Trial Arms

NameTypeDescriptionInterventions
AtezolizumabExperimentalParticipants will receive intravenous (IV) atezolizumab on Day 1 of each 21-day cycle for 16 cycles (up to 1 year).
  • Atezolizumab
ObservationNo InterventionParticipants will undergo observation starting on Day 1 for 16 cycles (up to 1 year).

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Histologically confirmed muscle-invasive UC (also termed transitional cell carcinoma)
                 of the bladder or upper urinary tract (i.e., renal pelvis or ureters)
    
              -  For participants treated with prior neoadjuvant chemotherapy: tumor stage of ypT2-4a
                 or ypN+ (ypT2-4 or ypN+ for participants with upper urinary tract UC) and M0
    
              -  For participants who have not received prior neoadjuvant chemotherapy: tumor stage of
                 pT3-4a or pN+ (pT3-4 or pN+ for participants with upper urinary tract UC) and M0
    
              -  Representative formalin-fixed paraffin-embedded tumor specimens from surgical
                 resection (i.e., radical cystectomy, nephroureterectomy, or lymph node dissection) in
                 paraffin blocks (blocks preferred) or at least 15 unstained slides, with an associated
                 pathology report, for central testing and determined to be evaluable for tumor
                 programmed death-ligand 1 (PD-L1) expression prior to study enrollment
    
              -  Absence of residual disease and absence of metastasis, as confirmed by a negative
                 baseline computed tomography (CT) or magnetic resonance imaging scan of the pelvis,
                 abdomen, and chest no more than 4 weeks prior to randomization
    
              -  Full recovery from cystectomy or nephroureterectomy within 14 weeks following surgery
    
              -  Eastern Cooperative Oncology Group performance status of less than or equal to (</=) 2
    
              -  Life expectancy greater than or equal to (>/=) 12 weeks
    
              -  Adequate hematologic and end-organ function
    
              -  For women who are not postmenopausal or surgically sterile: agreement to remain
                 abstinent or use contraceptive methods that result in a failure rate of less than (<)
                 1 percent (%) per year during the treatment period and for at least 5 months after the
                 last dose of atezolizumab
    
            Exclusion Criteria:
    
              -  Any approved anti-cancer therapy within 3 weeks prior to initiation of study treatment
    
              -  Adjuvant chemotherapy or radiation therapy for UC following surgical resection
    
              -  Treatment with any other investigational agent or participation in another clinical
                 trial with therapeutic intent within 28 days or five half-lives of the drug prior to
                 enrollment
    
              -  Malignancies other than UC within 5 years prior to Cycle 1, Day 1
    
              -  Pregnancy or breastfeeding
    
              -  Significant cardiovascular disease
    
              -  Severe infections within 4 weeks prior to Cycle 1, Day 1
    
              -  Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day
                 1
    
              -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to
                 chimeric or humanized antibodies or fusion proteins
    
              -  Known hypersensitivity 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 and/or active hepatitis B or hepatitis
                 C or tuberculosis
    
              -  Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1
    
              -  Prior treatment with cluster of differentiation 137 (CD137) agonists or immune
                 checkpoint blockade therapies, including anti-CD40, anti-cytotoxic
                 T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1),
                 and anti-PD-L1 therapeutic antibodies
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Disease-Free Survival (DFS), as Assessed by Investigator
    Time Frame:Randomization up to first occurrence of DFS event (up to approximately 50 months)
    Safety Issue:
    Description:DFS is defined as the time from randomization to the time of first occurrence of a DFS event. DFS events include: local (pelvic) recurrence of UC (including soft tissue and regional lymph nodes); urinary tract recurrence of UC (including all pathological stages and grades); distant metastasis of UC; or death from any cause. Tumor assessment will be performed using radiographic evaluations.

    Secondary Outcome Measures

    Measure:Overall Survival (OS)
    Time Frame:Randomization until death due to any cause (up to approximately 50 months)
    Safety Issue:
    Description:Overall survival is defined as the time from randomization to the date of death from any cause, regardless of whether the death occurs during study treatment or following treatment discontinuation.
    Measure:Disease-Specific Survival (DSS), as Assessed by Investigator
    Time Frame:Randomization until death due to UC (up to approximately 50 months)
    Safety Issue:
    Description:DSS is defined as the time from randomization until the date of death from UC.
    Measure:Distant Metastasis-Free Survival (DMFS)
    Time Frame:Randomization up to diagnosis of distant metastases or death from any cause (up to approximately 50 months)
    Safety Issue:
    Description:DMFS is defined as the time from randomization to the date of diagnosis of distant (that is, non-locoregional) metastases or death from any cause. Tumor assessment will be performed using radiographic evaluations.
    Measure:Non-Urinary Tract Recurrence-Free Survival (NURFS)
    Time Frame:Randomization up to time of first occurrence of a NURFS event (up to approximately 50 months)
    Safety Issue:
    Description:NURFS is defined as the time from randomization to the time of first occurrence of a NURFS event. NURFS events include: local (pelvic) recurrence of UC (including soft tissue and regional lymph nodes); distant metastasis of UC; or death from any cause. Tumor assessment will be performed using radiographic evaluations.
    Measure:Percentage of Participants With Adverse Events (AEs)
    Time Frame:Screening up to approximately 50 months
    Safety Issue:
    Description:Percentage of participants with at least one Adverse Event.
    Measure:Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
    Time Frame:Baseline up to approximately 50 months
    Safety Issue:
    Description:Percentage of participants with anti-therapeutic antibodies to atezolizumab.
    Measure:EuroQol 5-Dimension 5-Level (EQ-5D-5L) Visual Analogue Scale Score
    Time Frame:Day 1 of Cycle 1 up to approximately 50 months (Cycle length = 21 days)
    Safety Issue:
    Description:The EQ-5D-5L is a generic preference-based HRQoL questionnaire that provides a single index value for health status and is used to inform pharmacoeconomic evaluations and to measure general health status. Visual analog scale (VAS) allows the patient to indicate, on a scale of 0-100, how his or her health is on the day of assessment, with 100 being the "best imaginable health state" and 0 being the "worst imaginable health state."
    Measure:Minimum Observed Serum Atezolizumab Concentration (Cmin)
    Time Frame:Pre-dose (Hour 0) on Day 1 of Cycles 1, 2, 3, 4, every 8 cycles from Cycle 8, at treatment discontinuation, 120 days after treatment discontinuation (up to approximately 50 months))(Cycle length = 21 days)
    Safety Issue:
    Description:Minimum observed serum atezolizumab concentration (Cmin) prior to infusion on Day 1 of Cycles 1, 2, 3, and 4; every 8 cycles starting on Cycle 8; at treatment discontinuation; and at 120 days after the last dose of atezolizumab.
    Measure:Maximum Observed Serum Atezolizumab Concentration (Cmax)
    Time Frame:Day 1 of Cycle 1 (Cycle length = 21 days)
    Safety Issue:
    Description:Maximum observed serum atezolizumab concentration (Cmax) after infusion on Day 1 of Cycle 1.

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Active, not recruiting
    Lead Sponsor:Hoffmann-La Roche

    Last Updated

    April 2, 2021