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A Study of Atezolizumab Compared With Chemotherapy in Participants With Locally Advanced or Metastatic Urothelial Bladder Cancer [IMvigor211]

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT02302807
Collaborator
(none)
931
Enrollment
217
Locations
2
Arms
45.8
Actual Duration (Months)
4.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
931 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab (Anti-PD-L1 Antibody) Compared With Chemotherapy in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer After Failure With Platinum-Containing Chemotherapy
Actual Study Start Date :
Jan 13, 2015
Actual Primary Completion Date :
Mar 13, 2017
Actual Study Completion Date :
Nov 8, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A: Atezolizumab

Atezolizumab will be administered intravenously at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle. Participants will receive atezolizumab as long as they continue to experience clinical benefit in the opinion of the investigator until unacceptable toxicity or symptomatic deterioration attributed to disease progression as determined by the investigator.

Drug: Atezolizumab (MPDL3280A) [TECENTRIQ], an engineered anti-PDL1 antibody
Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on Day 1 of each 21-day cycle.
Other Names:
  • Tecentriq

    		•
    Active Comparator: Arm B: Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel)

    Participants randomized to the chemotherapy arm will receive vinflunine, paclitaxel, or docetaxel per the investigator's choice. Vinflunine 320 milligrams per square meter (mg/m^2), paclitaxel 175 mg/m^2, or docetaxel 75 mg/m^2 will be administered intravenously on Day 1 of each 21-day cycle until disease progression per standard RECIST v1.1 or unacceptable toxicity.

    Drug: Docetaxel
    Docetaxel 75 mg/m^2 will be administered intravenously on Day 1 of each 21-day cycle.

    Drug: Paclitaxel
    Paclitaxel 175 mg/m^2 will be administered intravenously on Day 1 of each 21-day cycle.

    Drug: Vinflunine
    Vinflunine 320 mg/m^2 will be administered intravenously on Day 1 of each 21-day cycle.

    Outcome Measures

    Primary Outcome Measures

    1. Overall Survival (OS) [Between randomization and death due to any cause, up to approximately 25 months after first participant enrolled]

      OS was defined as time from randomization to death from any cause.

    Secondary Outcome Measures

    1. Progression-free Survival (PFS) as Determined by the Investigator With Use of RECIST v1.1 [Up to approximately 25 months after first participant enrolled]

      PFS was defined as the time between the date of randomization and the date of first documented progression of disease (PD) or death, whichever occurred first. PD was determined on the basis of investigator assessment with use of RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters had to demonstrate an absolute increase of >/= 5 millimeters (mm).

    2. Unconfirmed Duration of Response (DOR) as Determined by the Investigator With Use of RECIST v1.1 [Up to approximately 25 months after first participant enrolled]

      DOR was defined as the time from first occurrence of a CR or PR, whichever came first, to first documented PD or death, whichever occurred first. Disease progression was determined on the basis of investigator assessment with use of RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 mm.

    3. Percentage of Participants With Adverse Events (AEs) [Up to approximately 46 months after first participant enrolled]

      An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

    4. Percentage of Participants With Post-Baseline Anti-therapeutic Antibodies (ATA) to Atezolizumab [Predose (0 hours) on Day 1 of Cycles 1, 2, 3, 4 and every 8 cycles thereafter; at treatment discontinuation (up to 25 months); at 120 days after last dose of atezolizumab (up to 25 months; each cycle is 21 days)]

      Participants were considered post-baseline ATA positive if they had post-baseline ATAs to Atezolizumab that were treatment-induced or treatment-enhanced. Participants had treatment-induced ATAs if they had a baseline-negative ATA result and developed ATAs at any time after initial drug administration. Participants had treatment-enhanced ATAs if they had a baseline-positive ATA result that showed an enhanced signal that was >/= 0.60 titer units at any time after initial drug initiation.

    5. Minimum Observed Serum Atezolizumab Concentration (Cmin) [Predose (0 hours) on Day 1 of Cycles 1, 2, 3, 4 and every 8 cycles thereafter; at treatment discontinuation (up to 25 months); at 120 days after last dose of atezolizumab (up to 25 months; each cycle is 21 days)]

      Cmin was measured for all participants that received at least one dose of Atezolizumab.

    6. Percentage of Participants With Unconfirmed Objective Response Rate (ORR) as Determined by the Investigator With Use of Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) [Up to approximately 25 months after first participant enrolled]

      ORR was defined as the percentage of participants, who had an objective response. Objective response was defined as either a complete response (CR) or partial response (PR) as determined by the investigator with use of Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). Objective response in this study did not need to be a confirmed response. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. ORR=CR+PR

    7. Maximum Observed Serum Atezolizumab Concentration (Cmax) [30 minutes post dose on Day 1 of Cycles 1]

      Cmax was measured for all participants that received at least one dose of Atezolizumab.

    8. Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) Score: Global Health Status Scale [Cycle 1 Day 1 (prior to any health care interaction), on Day 1 of each subsequent cycle, and at 30 days after the last treatment dose (Up to approximately 25 months; each cycle is 21 days)]

      The EORTC QLQ-C30 includes five functional scales (physical, role, cognitive, emotional, social); a global health status (GHS)/quality of life (QoL) scale; and items measuring fatigue, pain, nausea and vomiting, dyspnea, appetite loss, sleep disturbance, constipation, diarrhea, and financial difficulties. The score range for each scale and single-item measure is 0 to 100, where higher scores indicate a higher response level (i.e., better functioning, better QoL, worse symptoms). Key scales included physical functioning, and fatigue, and GHS.

    9. Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) Score: Physical Functioning Scale [Cycle 1 Day 1 (prior to any health care interaction), on Day 1 of each subsequent cycle, and at 30 days after the last treatment dose (Up to approximately 25 months; each cycle is 21 days)]

      The EORTC QLQ-C30 includes five functional scales (physical, role, cognitive, emotional, social); a global health status (GHS)/quality of life (QoL) scale; and items measuring fatigue, pain, nausea and vomiting, dyspnea, appetite loss, sleep disturbance, constipation, diarrhea, and financial difficulties. The score range for each scale and single-item measure is 0 to 100, where higher scores indicate a higher response level (i.e., better functioning, better QoL, worse symptoms). Key scales included physical functioning, and fatigue, and GHS.

    10. Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) Score: Fatigue Symptom Scale [Cycle 1 Day 1 (prior to any health care interaction), on Day 1 of each subsequent cycle, and at 30 days after the last treatment dose (Up to approximately 25 months; each cycle is 21 days)]

      The EORTC QLQ-C30 includes five functional scales (physical, role, cognitive, emotional, social); a global health status (GHS)/quality of life (QoL) scale; and items measuring fatigue, pain, nausea and vomiting, dyspnea, appetite loss, sleep disturbance, constipation, diarrhea, and financial difficulties. The score range for each scale and single-item measure is 0 to 100, where higher scores indicate a higher response level (i.e., better functioning, better QoL, worse symptoms). Key scales included physical functioning, and fatigue, and GHS.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Georgetown University Medical Center Lombardi Cancer Center Washington District of Columbia United States 20007
    2 Emory University; Winship Cancer Institute Atlanta Georgia United States 30308
    3 Comprehensive Cancer Centers of Nevada Las Vegas Nevada United States 89128
    4 Duke Cancer Center Durham North Carolina United States 27710
    5 Bon Secours - St. Francis Hospital Greenville South Carolina United States 29607
    6 Vanderbilt-Ingram Cancer Ctr Nashville Tennessee United States 37232
    7 Royal Brisbane and Women's Hospital; Medical Oncology Herston Queensland Australia 4029
    8 Royal Adelaide Hospital; Oncology Adelaide South Australia Australia 5000
    9 Monash Medical Centre; Oncology Clayton Victoria Australia 3168
    10 Austin and Repatriation Medical Centre; Cancer Services Melbourne Victoria Australia 3084
    11 Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Abt. für Onkologie Wien Austria 1090
    12 Kaiser-Franz-Josef-Spital; Zent.Onkologie und Hamatologie Wien Austria 1100
    13 ZNA Middelheim Antwerpen Belgium 2020
    14 Institut Jules Bordet Bruxelles Belgium 1000
    15 UZ Gent Gent Belgium 9000
    16 UZ Leuven Gasthuisberg Leuven Belgium 3000
    17 Tom Baker Cancer Centre-Calgary Calgary Alberta Canada T2N 4N2
    18 Bcca - Cancer Center Southern Interior Kelowna British Columbia Canada V1Y 5L3
    19 BCCA-Vancouver Cancer Centre Vancouver British Columbia Canada V5Z 4E6
    20 Bcca - Vancouver Island Cancer Centre; Oncology Victoria British Columbia Canada V8R 6V5
    21 Royal Victoria Hospital Barrie Ontario Canada L4M 6M2
    22 London Regional Cancer Centre London Ontario Canada N6A 4L6
    23 Lakeridge Health Oshawa; Oncology Oshawa Ontario Canada L1G 2B9
    24 The Ottawa Hospital Cancer Centre; Oncology Ottawa Ontario Canada K1H 8L6
    25 Sault Area Hospitals Sault Ste Marie Ontario Canada P6A 2C4
    26 Sunnybrook Odette Cancer Centre Toronto Ontario Canada M4N 3M5
    27 McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology Montreal Quebec Canada H3T 1E2
    28 Masarykuv onkologicky ustav Brno Czechia 656 53
    29 Fakultni nemocnice Olomouc Olomouc Czechia 775 20
    30 MULTISCAN, s.r.o., Radiologicke centrum Pardubice Pardubice Czechia 532 03
    31 Vseobecna fakultni nemocnice v Praze Praha 2 Czechia 128 08
    32 Fakultni nemocnice Kralovske Vinohrady Praha Czechia 100 34
    33 Herlev Hospital; Onkologisk afdeling Herlev Denmark 2730
    34 Rigshospitalet; Onkologisk Klinik København Ø Denmark 2100
    35 Docrates Cance Center Helsinki Finland 00180
    36 Turku University Central Hospital; Urology clinic Turku Finland 20520
    37 Ico - Paul Papin Angers France 49000
    38 Institut Sainte Catherine;Recherche Clinique Avignon France 84918
    39 Chr De Besancon - Hopital Jean Minjoz Besancon France 25030
    40 Hopital Saint Andre Bordeaux France 33075
    41 Institut Bergonie; Oncologie Bordeaux France 33076
    42 Centre Francois Baclesse; Recherche Clinique Caen France 14076
    43 CHU Henri Mondor; Service d'Oncologie Medicale Creteil France 94010
    44 Clinique Chenieux; Oncology Limoges France 87039
    45 Centre Leon Berard; Departement Oncologie Medicale Lyon France 69373
    46 Institut J Paolii Calmettes Marseille France 13009
    47 Institut régional du Cancer Montpellier Montpellier France 34298
    48 Centre D'Oncologie de Gentilly; Oncology Nancy France 54100
    49 Centre Antoine Lacassagne Nice France 06189
    50 CHU De Nimes, Hopital Caremeau; Service De Neurologie Du Prof. Pierre Labauge Nimes France 30029
    51 Hopital Cochin; Unite Fonctionnelle D Oncologie Paris France 75014
    52 Institut Curie; Recherche Clinique Paris France 75231
    53 Hopital Saint Louis; Oncologie Medicale Paris France 75475
    54 Hopital Europeen Georges Pompidou; Service D'Oncologie Medicale Paris France 75908
    55 Centre Hospitalier Lyon Sud Pierre Benite France 69495
    56 CHU de Rouen - Hôpital Charles Nicolle Rouen France 76031
    57 ICO - Site René Gauducheau Saint Herblain France 44805
    58 Hopital Hautepierre; Hematologie Oncologie Strasbourg France 67098
    59 Hopital Foch; Oncologie Suresnes France 92151
    60 Institut Claudius Regaud; Departement Oncologie Medicale Toulouse France 31059
    61 Institut Gustave Roussy; Departement Oncologie Medicale Villejuif France 94805
    62 Uniklinik RWTH Aachen; Klinik für Urologie Aachen Germany 52074
    63 Charité - Universitätsmedizin Berlin; CC 8: Chirurgische Medizin; Klinik für Urologie Berlin Germany 12200
    64 Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik für Urologie Dresden Germany 01307
    65 Universitätsklinikum Düsseldorf; Urologische Klinik Düsseldorf Germany 40225
    66 Friedrich-Alexander-Universität Erlangen-Nürnberg; Medizinische Klinik V Erlangen Germany 91054
    67 Universitätsklinikum Freiburg; Chirurgische Klinik; Abteilung Urologie Freiburg Germany 79106
    68 Universitätsmedizin Göttingen Georg-August-Universität; Klinik für Urologie Göttingen Germany 37075
    69 Universitätsklinikum Hamburg-Eppendorf Onkologisches Zentrum Medizinische Klinik II Hamburg Germany 20246
    70 Nationales Centrum für Tumorerkrankungen Heidelberg (NCT); Thoraxklinik Heidelberg Heidelberg Germany 69120
    71 Universitätsklinikum des Saarlandes; Klinik für Urologie und Kinderurologie Homburg/Saar Germany 66424
    72 Universitätsklinikum Magdeburg A.ö.R., Klinik f. Urologie u. Kinderurologie Magdeburg Germany 39120
    73 Medizinische Fakultät Mannheim, Universitätsklinikum Mannheim, Klinik für Urologie Mannheim Germany 68167
    74 Klinikum rechts der Isar der TU München; Urologische Klinik und Poliklinik München Germany 81675
    75 Universitätsklinikum Tübingen; Klinik für Urologie Tübingen Germany 72076
    76 Universitätsklinikum Ulm; Klinik für Urologie Ulm Germany 89081
    77 Alexandras General Hospital of Athens; Oncology Department Athens Greece 115 28
    78 Univ General Hosp Heraklion; Medical Oncology Heraklion Greece 711 10
    79 University Hospital of Patras Medical Oncology Patras Greece 265 04
    80 Euromedical General Clinic of Thessaloniki; Oncology Department Thessaloniki Greece 546 45
    81 Semmelwies University of Medicine; Urology Dept. Budapest Hungary 1082
    82 Orszagos Onkologiai Intezet; "C" Belgyógyászati-Onkológiai és Klinikai Farmakológiai Osztály Budapest Hungary 1122
    83 Uzsoki Utcai Korhaz Budapest Hungary 1145
    84 Kecskemeti Onkoradilogai Centrum Kecskemét Hungary 6000
    85 Hetenyi Geza County Hospital; Onkologiai Kozpont Szolnok Hungary 5004
    86 Azienda Ospedaliera A. Cardarelli; Dip. Oncopneumoematologico Napoli Campania Italy 80131
    87 IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica Meldola Emilia-Romagna Italy 47014
    88 A.O. Universitaria Policlinico Di Modena; Oncologia Modena Emilia-Romagna Italy 41100
    89 A.O. Universitaria S. Maria Della Misericordia Di Udine; Oncologia Udine Friuli-Venezia Giulia Italy 33100
    90 Azienda Ospedaliera San Camillo Forlanini; Oncologia Medica Roma Lazio Italy 00152
    91 Asst Papa Giovanni XXIII; Oncologia Medica Bergamo Lombardia Italy 24127
    92 ASST DI CREMONA; Dip. Medicina - S.C. Oncologia Cremona Lombardia Italy 26100
    93 Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2 Milano Lombardia Italy 20133
    94 Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico Candiolo Piemonte Italy 10060
    95 IRCCS Ospedale Casa Sollievo Della Sofferenza; Oncologia San Giovanni Rotondo Puglia Italy 71013
    96 Casa Di Cura Di Alta Specialita La Maddalena; Dept. Oncologico Di Iii Livello Palermo Sicilia Italy 90146
    97 Azienda USL8 Arezzo-Presidio Ospedaliero 1 San Donato;U.O.C. Oncologia Arezzo Toscana Italy 52100
    98 Azienda Ospedaliero-Universitaria Careggi;S.C. Oncologia Medica 1 Firenze Toscana Italy 50139
    99 Nagoya University Hospital; Urology Aichi Japan 466-8560
    100 Hirosaki University School of Medicine & Hospital; Urology Aomori Japan 036-8563
    101 Chiba Cancer Center; Urology Chiba Japan 260-8717
    102 National Cancer Center Hospital East; Breast and Medical Oncology Chiba Japan 277-8577
    103 National Hospital Organization Shikoku Cancer Center; Urology Ehime Japan 791-0280
    104 Harasanshin Hospital; Urology Fukuoka Japan 812-0033
    105 Kyushu University Hospital; Urology Fukuoka Japan 812-8582
    106 Gunma University Hospital; Urology Gunma Japan 371-8511
    107 Hiroshima City Hiroshima Citizens Hospital; Urology Hiroshima Japan 730-8518
    108 Sapporo Medical University Hospital; Urology Hokkaido Japan 060-8543
    109 Hokkaido University Hospital; Urology Hokkaido Japan 060-8648
    110 University of Tsukuba Hospital; Urology Ibaraki Japan 305-8576
    111 Iwate Medical University Hospital; Urology Iwate Japan 020-8505
    112 Yokohama City University Hospital; Urology Kanagawa Japan 236-0004
    113 Kumamoto University Hospital; Urology Kumamoto Japan 860-8556
    114 Niigata Cancer Center Hospital;Urology Niigata Japan 951-8566
    115 Osaka International Cancer Institute; Urology Osaka Japan 541-8567
    116 Osaka University Hospital; Urology Osaka Japan 565-0871
    117 Kindai University Hospital; Urology Osaka Japan 589-8511
    118 Shizuoka Cancer Center; Urology Shizuoka Japan 411-8777
    119 Tokushima University Hospital; Urology Tokushima Japan 770-8503
    120 National Cancer Center Hospital; Urology Tokyo Japan 104-0045
    121 Toranomon Hospital; Medical Oncology Tokyo Japan 105-8470
    122 Nippon Medical School Hospital; Urology Tokyo Japan 113-8603
    123 The Cancer Institute Hospital, JFCR; Urology Tokyo Japan 135-8550
    124 Seoul National University Hospital Seoul Korea, Republic of 03080
    125 Asan Medical Center - Oncology Seoul Korea, Republic of 05505
    126 Samsung Medical Center Seoul Korea, Republic of 6351
    127 The Netherlands Cancer Institute - Antoni Van Leeuwenhoekziekenhuis Amsterdam Netherlands 1066 CX
    128 Spaarne Ziekenhuis; Inwendige Geneeskunde Hoofddorp Netherlands 2134 TM
    129 Maastricht University Medical Centre; Medical Oncology Maastricht Netherlands 6229 HX
    130 St. Antonius Ziekenhuis Nieuwegein Nieuwegein Netherlands 3430 EM
    131 Isala Klinieken Zwolle Netherlands 8011 JW
    132 Sørlandet Sykehus Kristiansand Kristiansand Norway 4604
    133 Uni Hospital of Tromso; Dept. of Oncology Tromsø Norway 9019
    134 St. Olavs Hospital; Kreftavdelingen Trondheim Norway 7000
    135 Medical University of Bialystok; Oncology clinic Bialystok Poland 15-027
    136 Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii Gdansk Poland 80-214
    137 COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej Lublin Poland 20-090
    138 Oddzial Chemioterapii Szpitala Klinicznego Nr 1 w Poznaniu Poznan Poland 60-569
    139 Centrum onkologii Instytutu im. Marii Sklodowskiej-Curie; Klinika Nowotworow Ukladu Moczowego Warszawa Poland 02-781
    140 Uniwersytecki Szpital Kliniczny im. Jana Miklulicza-Radeckiego we Wrocławiu; Departament Of Urology Wroclaw Poland 50-556
    141 Hospital de Santa Maria; Servico de Oncologia Medica Lisboa Portugal 1649-035
    142 Hospital Beatriz Angelo; Departamento de Oncologia Loures Portugal 2674-514
    143 IPO do Porto; Servico de Oncologia Medica Porto Portugal 4200-072
    144 Spitalul Judetean de Urgenta Dr Constantin Opris Baia Mare Romania 430031
    145 Institute Of Oncology Bucharest; Medical Oncology Bucharest Romania 022338
    146 Institut Oncologic Ion Chiricuta; Departament Radioterapie Cluj-napoca Romania 400015
    147 Oncology Center Sf. Nectarie Craiova Romania 200347
    148 Euroclinic Center of Oncology SRL Iasi Romania 700106
    149 Spital Clinic Judetean Mures; Oncologie Targu Mures Romania 540142
    150 ONCOMED - Medical Centre Timisoara Romania 300239
    151 GBUZ Nizhegorodskay Region: Clinical Diagnostic Center Nizhni Novgorod Niznij Novgorod Russian Federation 603001
    152 Altai Regional Oncological Center Barnaul Russian Federation 656049
    153 Federal State Institution, Moscow Research Oncology Institute n.a. P.A. Hertzen; Oncourology Moscow Russian Federation 125284
    154 St. Petersburg Oncology Hospital St Petersburg Russian Federation 198255
    155 SBI of Healthcare of Stavropol region Stavropol Regional Clinical Oncology Dispensary Stavropol Russian Federation 355045
    156 Clinical Center of Serbia; Clinic of Urology Belgrade Serbia 11000
    157 Institute for Oncology and Radiology of Serbia; Medical Oncology Belgrade Serbia 11000
    158 Oncology Institute of Vojvodina Sremska Kamenica Serbia 21204
    159 Institute of Oncology Ljubljana Ljubljana Slovenia 1000
    160 Corporacio Sanitaria Parc Tauli; Servicio de Oncologia Sabadell Barcelona Spain 08208
    161 Hospital Universitario Reina Sofia; Servicio de Oncologia Córdoba Cordoba Spain 14004
    162 Hospital Universitario Son Espases; Servicio de Oncologia Palma De Mallorca Islas Baleares Spain 07014
    163 Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia Santiago de Compostela LA Coruña Spain 15706
    164 Clinica Universitaria de Navarra; Servicio de Oncologia Pamplona Navarra Spain 31008
    165 Hospital Univ Vall d'Hebron; Servicio de Oncologia Barcelona Spain 08035
    166 Hospital Clinic i Provincial; Servicio de Farmacia Barcelona Spain 08036
    167 Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia Barcelona Spain 08041
    168 Institut Catala d Oncologia Hospital Duran i Reynals Barcelona Spain 08908
    169 Hospital San Pedro De Alcantara; Servicio de Oncologia Caceres Spain 10003
    170 Hospital General Universitario Gregorio Marañon; Servicio de Oncologia Madrid Spain 28007
    171 Hospital Ramon y Cajal; Servicio de Oncologia Madrid Spain 28034
    172 Hospital Universitario Clínico San Carlos; Servicio de Oncologia Madrid Spain 28040
    173 Hospital Universitario 12 de Octubre; Servicio de Oncologia Madrid Spain 28041
    174 Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia Malaga Spain 29010
    175 Hospital de Navarra; Servicio de Oncologia Navarra Spain 31008
    176 Hospital Universitario Virgen del Rocio; Servicio de Oncologia Sevilla Spain 41013
    177 Hospital General Universitario de Valencia; Servicio de oncologia Valencia Spain 41014
    178 Hospital Clínico Universitario de Valencia; Servicio de Oncología Valencia Spain 46010
    179 Sahlgrenska Universitetssjukhuset; Jubileumskliniken Göteborg Sweden 413 45
    180 Karolinska Hospital; Oncology - Radiumhemmet Stockholm Sweden 171 76
    181 Norrlands Uni Hospital; Onkologi Avd. Umea Sweden 090185
    182 Inselspital Bern; Universitätsklinik für medizinische Onkologie Bern Switzerland 3010
    183 Kantonsspital Graubünden;Onkologie und Hämatologie Chur Switzerland 7000
    184 HUG; Oncologie Geneve Switzerland 1211
    185 Kantonsspital St. Gallen; Onkologie/Hämatologie St. Gallen Switzerland 9007
    186 UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie Zürich Switzerland 8091
    187 China Medical University Hospital; Urology Taichung Taiwan 40447
    188 Taichung Veterans General Hospital; Division of Urology Taichung Taiwan 407
    189 National Taiwan Uni Hospital; Dept of Oncology Taipei Taiwan 100
    190 TAIPEI VETERANS GENERAL HOSPITAL, Urology Taipei Taiwan 11217
    191 Uludag Uni Hospital; Oncology Bursa Turkey 16059
    192 Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department Edirne Turkey 22770
    193 Bezmialem Vakif Univ Medical Istanbul Turkey 34286
    194 Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology Istanbul Turkey 34300
    195 Istanbul VKV American Hospital; Medical Oncology Istanbul Turkey 34365
    196 Ege Uni Medical Faculty Hospital; Oncology Dept Izmir Turkey 35100
    197 Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department Malatya Turkey 44280
    198 Hacettepe Uni Medical Faculty Hospital; Oncology Dept Sıhhiye, Ankara Turkey 06100
    199 University Hospital Birmingham The Cancer Centre, Queen Elizabeth Hospital Birmingham United Kingdom B15 2TH
    200 Bristol Haematology and Oncology Centre Bristol United Kingdom BS2 8ED
    201 Addenbrooke's Hospital Cambridge United Kingdom CB2 0QQ
    202 Cheltenham General Hospital Cheltenham United Kingdom GL53 7AN
    203 University Hospital coventry; Oncology Department Coventry United Kingdom CV2 2DX
    204 Royal Devon & Exeter Hospital; Oncology Centre Exeter United Kingdom EX2 5DW
    205 Royal Lancaster Infirmary, Morecambe Bay Hospitals Nhs Trust Lancaster United Kingdom LA1 4RP
    206 St James Institute of Oncology Leeds United Kingdom LS9 7TF
    207 Leicester Royal Infirmary; Dept. of Medical Oncology Leicester United Kingdom LE1 5WW
    208 Barts and The London London United Kingdom EC1M 6BQ
    209 Royal Free Hospital; Dept of Oncology London United Kingdom NW3 2QG
    210 Northern Centre for Cancer Care; Northern Centre for Cancer Care Newcastle Upon Tyne United Kingdom NE7 7DN
    211 Nottingham City Hospital Nottingham United Kingdom NG5 1PB
    212 Churchill Hospital Oxford United Kingdom OX3 7LJ
    213 Scunthorpe General Hospital; Dept of Oncology Scunthorpe United Kingdom DN16 7BH
    214 Southampton General Hospital; Medical Oncology Southampton United Kingdom SO16 6YD
    215 Royal Marsden Hospital; Dept of Medical Oncology Sutton United Kingdom SM2 5PT
    216 Royal Cornwall Hospital Truro United Kingdom TR1 3LQ
    217 The Clatterbridge Cancer Centre NHS Foundation Trust Wirral United Kingdom CH63 4JY

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT02302807
    Other Study ID Numbers:
    • GO29294
    • 2014-003231-19
    First Posted:
    Nov 27, 2014
    Last Update Posted:
    Aug 1, 2019
    Last Verified:
    Jul 1, 2019
    Additional relevant MeSH terms:
    Urinary Bladder Neoplasms
    Paclitaxel
    Docetaxel
    Atezolizumab
    Antibodies

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel) Atezolizumab
    Arm/Group Description Participants randomized to the chemotherapy arm received vinflunine, paclitaxel, or docetaxel per the investigators choice. Vinflunine 320 milligrams per square meter (mg/m^2), paclitaxel 175 mg/m^2, or docetaxel 75 mg/m^2 were administered intravenously on Day 1 of each 21-day cycle until disease progression per standard RECIST v1.1 or unacceptable toxicity. Atezolizumab was administered intravenously at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle. Participants received atezolizumab as long as they continued to experience clinical benefit in the opinion of the investigator until unacceptable toxicity or symptomatic deterioration attributed to disease progression as determined by the investigator.
    Period Title: Overall Study
    STARTED 464 467
    Received Treatment 443 459
    COMPLETED 0 0
    NOT COMPLETED 464 467

    Baseline Characteristics

    Arm/Group Title Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel) Atezolizumab Total
    Arm/Group Description Participants randomized to the chemotherapy arm received vinflunine, paclitaxel, or docetaxel per the investigators choice. Vinflunine 320 milligrams per square meter (mg/m^2), paclitaxel 175 mg/m^2, or docetaxel 75 mg/m^2 were administered intravenously on Day 1 of each 21-day cycle until disease progression per standard RECIST v1.1 or unacceptable toxicity. Atezolizumab was administered intravenously at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle. Participants received atezolizumab as long as they continued to experience clinical benefit in the opinion of the investigator until unacceptable toxicity or symptomatic deterioration attributed to disease progression as determined by the investigator. Total of all reporting groups
    Overall Participants 464 467 931
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    66.1
    (9.3)
    65.9
    (9.6)
    66.0
    (9.4)
    Sex: Female, Male (Count of Participants)
    Female
    103
    22.2%
    110
    23.6%
    213
    22.9%
    Male
    361
    77.8%
    357
    76.4%
    718
    77.1%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    16
    3.4%
    13
    2.8%
    29
    3.1%
    Not Hispanic or Latino
    368
    79.3%
    363
    77.7%
    731
    78.5%
    Unknown or Not Reported
    80
    17.2%
    91
    19.5%
    171
    18.4%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    55
    11.9%
    63
    13.5%
    118
    12.7%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    2
    0.4%
    1
    0.2%
    3
    0.3%
    White
    336
    72.4%
    335
    71.7%
    671
    72.1%
    More than one race
    1
    0.2%
    0
    0%
    1
    0.1%
    Unknown or Not Reported
    70
    15.1%
    68
    14.6%
    138
    14.8%

    Outcome Measures

    1. Primary Outcome
    Title Overall Survival (OS)
    Description OS was defined as time from randomization to death from any cause.
    Time Frame Between randomization and death due to any cause, up to approximately 25 months after first participant enrolled

    Outcome Measure Data

    Analysis Population Description
    Intent To Treat (ITT) was defined as all randomized participants, irrespective of whether the assigned treatment was actually received.
    Arm/Group Title IC2/3 Chemotherapy IC2/3 Atezolizumab IC1/2/3 Chemotherapy IC1/2/3 Atezolizumab Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel) Atezolizumab
    Arm/Group Description PD-L1 immunohistochemistry (IHC) score of IC2/3 PD-L1 immunohistochemistry (IHC) score of IC2/3 PD-L1 immunohistochemistry (IHC) score of IC1/2/3 PD-L1 immunohistochemistry (IHC) score of IC1/2/3 Participants randomized to the chemotherapy arm received vinflunine, paclitaxel, or docetaxel per the investigators choice. Vinflunine 320 milligrams per square meter (mg/m^2), paclitaxel 175 mg/m^2, or docetaxel 75 mg/m^2 were administered intravenously on Day 1 of each 21-day cycle until disease progression per standard RECIST v1.1 or unacceptable toxicity. Atezolizumab was administered intravenously at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle. Participants received atezolizumab as long as they continued to experience clinical benefit in the opinion of the investigator until unacceptable toxicity or symptomatic deterioration attributed to disease progression as determined by the investigator.
    Measure Participants 118 116 309 316 464 467
    Median (95% Confidence Interval) [Months]
    10.6
    11.1
    8.2
    8.9
    8.0
    8.6
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection IC2/3 Chemotherapy, IC2/3 Atezolizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4134
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.87
    Confidence Interval (2-Sided) 95%
    0.63 to 1.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection IC1/2/3 Chemotherapy, IC1/2/3 Atezolizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.87
    Confidence Interval (2-Sided) 95%
    0.71 to 1.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel), Atezolizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.85
    Confidence Interval (2-Sided) 95%
    0.73 to 0.99
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Progression-free Survival (PFS) as Determined by the Investigator With Use of RECIST v1.1
    Description PFS was defined as the time between the date of randomization and the date of first documented progression of disease (PD) or death, whichever occurred first. PD was determined on the basis of investigator assessment with use of RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters had to demonstrate an absolute increase of >/= 5 millimeters (mm).
    Time Frame Up to approximately 25 months after first participant enrolled

    Outcome Measure Data

    Analysis Population Description
    Intent To Treat (ITT) was defined as all randomized participants, irrespective of whether the assigned treatment was actually received.
    Arm/Group Title Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel) Atezolizumab IC2/3 Chemotherapy IC2/3 Atezolizumab IC1/2/3 Chemotherapy IC1/2/3 Atezolizumab
    Arm/Group Description Participants randomized to the chemotherapy arm received vinflunine, paclitaxel, or docetaxel per the investigators choice. Vinflunine 320 milligrams per square meter (mg/m^2), paclitaxel 175 mg/m^2, or docetaxel 75 mg/m^2 were administered intravenously on Day 1 of each 21-day cycle until disease progression per standard RECIST v1.1 or unacceptable toxicity. Atezolizumab was administered intravenously at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle. Participants received atezolizumab as long as they continued to experience clinical benefit in the opinion of the investigator until unacceptable toxicity or symptomatic deterioration attributed to disease progression as determined by the investigator. PD-L1 immunohistochemistry (IHC) score of IC2/3 PD-L1 immunohistochemistry (IHC) score of IC2/3 PD-L1 immunohistochemistry (IHC) score of IC1/2/3 PD-L1 immunohistochemistry (IHC) score of IC1/2/3
    Measure Participants 464 467 118 116 309 316
    Median (95% Confidence Interval) [months]
    4.0
    2.1
    4.2
    2.4
    4.1
    2.1
    3. Secondary Outcome
    Title Unconfirmed Duration of Response (DOR) as Determined by the Investigator With Use of RECIST v1.1
    Description DOR was defined as the time from first occurrence of a CR or PR, whichever came first, to first documented PD or death, whichever occurred first. Disease progression was determined on the basis of investigator assessment with use of RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 mm.
    Time Frame Up to approximately 25 months after first participant enrolled

    Outcome Measure Data

    Analysis Population Description
    DOR analyses was performed on the subset of patients who achieved an objective response.
    Arm/Group Title Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel) Atezolizumab IC2/3 Chemotherapy IC2/3 Atezolizumab IC1/2/3 Chemotherapy IC1/2/3 Atezolizumab
    Arm/Group Description Participants randomized to the chemotherapy arm received vinflunine, paclitaxel, or docetaxel per the investigators choice. Vinflunine 320 milligrams per square meter (mg/m^2), paclitaxel 175 mg/m^2, or docetaxel 75 mg/m^2 were administered intravenously on Day 1 of each 21-day cycle until disease progression per standard RECIST v1.1 or unacceptable toxicity. Atezolizumab was administered intravenously at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle. Participants received atezolizumab as long as they continued to experience clinical benefit in the opinion of the investigator until unacceptable toxicity or symptomatic deterioration attributed to disease progression as determined by the investigator. PD-L1 immunohistochemistry (IHC) score of IC2/3 PD-L1 immunohistochemistry (IHC) score of IC2/3 PD-L1 immunohistochemistry (IHC) score of IC1/2/3 PD-L1 immunohistochemistry (IHC) score of IC1/2/3
    Measure Participants 96 71 34 30 68 51
    Median (95% Confidence Interval) [months]
    5.3
    21.7
    6.4
    13.0
    5.5
    13
    4. Secondary Outcome
    Title Percentage of Participants With Adverse Events (AEs)
    Description An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
    Time Frame Up to approximately 46 months after first participant enrolled

    Outcome Measure Data

    Analysis Population Description
    Safety analyses was performed on all randomized patients who received any amount of study treatment, with patients grouped according to whether any amount of atezolizumab was received including the case when atezolizumab was received in error.
    Arm/Group Title Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel) Atezolizumab IC2/3 Chemotherapy IC2/3 Atezolizumab IC1/2/3 Chemotherapy IC1/2/3 Atezolizumab
    Arm/Group Description Participants randomized to the chemotherapy arm received vinflunine, paclitaxel, or docetaxel per the investigators choice. Vinflunine 320 milligrams per square meter (mg/m^2), paclitaxel 175 mg/m^2, or docetaxel 75 mg/m^2 were administered intravenously on Day 1 of each 21-day cycle until disease progression per standard RECIST v1.1 or unacceptable toxicity. Atezolizumab was administered intravenously at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle. Participants received atezolizumab as long as they continued to experience clinical benefit in the opinion of the investigator until unacceptable toxicity or symptomatic deterioration attributed to disease progression as determined by the investigator. PD-L1 immunohistochemistry (IHC) score of IC2/3 PD-L1 immunohistochemistry (IHC) score of IC2/3 PD-L1 immunohistochemistry (IHC) score of IC1/2/3 PD-L1 immunohistochemistry (IHC) score of IC1/2/3
    Measure Participants 443 459 112 114 297 312
    Number [percentage]
    98.2
    95.0
    98.2
    96.5
    98.7
    96.2
    5. Secondary Outcome
    Title Percentage of Participants With Post-Baseline Anti-therapeutic Antibodies (ATA) to Atezolizumab
    Description Participants were considered post-baseline ATA positive if they had post-baseline ATAs to Atezolizumab that were treatment-induced or treatment-enhanced. Participants had treatment-induced ATAs if they had a baseline-negative ATA result and developed ATAs at any time after initial drug administration. Participants had treatment-enhanced ATAs if they had a baseline-positive ATA result that showed an enhanced signal that was >/= 0.60 titer units at any time after initial drug initiation.
    Time Frame Predose (0 hours) on Day 1 of Cycles 1, 2, 3, 4 and every 8 cycles thereafter; at treatment discontinuation (up to 25 months); at 120 days after last dose of atezolizumab (up to 25 months; each cycle is 21 days)

    Outcome Measure Data

    Analysis Population Description
    ATA evaluable population is defined as patients who received atezolizumab treatment and had at least one post-treatment ATA result.
    Arm/Group Title Atezolizumab IC1/2/3 Atezolizumab IC2/3 Atezolizumab
    Arm/Group Description Atezolizumab was administered intravenously at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle. Participants received atezolizumab as long as they continued to experience clinical benefit in the opinion of the investigator until unacceptable toxicity or symptomatic deterioration attributed to disease progression as determined by the investigator. PD-L1 immunohistochemistry (IHC) score of IC2/3 PD-L1 immunohistochemistry (IHC) score of IC2/3
    Measure Participants 427 289 106
    Number [percentage of participants]
    33.3
    7.2%
    35.0
    7.5%
    33.0
    3.5%
    6. Secondary Outcome
    Title Minimum Observed Serum Atezolizumab Concentration (Cmin)
    Description Cmin was measured for all participants that received at least one dose of Atezolizumab.
    Time Frame Predose (0 hours) on Day 1 of Cycles 1, 2, 3, 4 and every 8 cycles thereafter; at treatment discontinuation (up to 25 months); at 120 days after last dose of atezolizumab (up to 25 months; each cycle is 21 days)

    Outcome Measure Data

    Analysis Population Description
    The PK-evaluable population is defined as patients who received atezolizumab treatment and had at least one measureable PK concentration.
    Arm/Group Title Atezolizumab
    Arm/Group Description Atezolizumab was administered intravenously at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle. Participants received atezolizumab as long as they continued to experience clinical benefit in the opinion of the investigator until unacceptable toxicity or symptomatic deterioration attributed to disease progression as determined by the investigator.
    Measure Participants 467
    Cycle 2, day 1
    67.5
    (29.1)
    Cycle 3, day 1
    95.1
    (46.5)
    Cycle 4, day 1
    122
    (56.9)
    Cycle 8, day 1
    159
    (72.4)
    Cycle 16, day 1
    190
    (94.7)
    Cycle 24, day 1
    190
    (98.7)
    Cycle 32, day 1
    223
    (87.4)
    7. Secondary Outcome
    Title Percentage of Participants With Unconfirmed Objective Response Rate (ORR) as Determined by the Investigator With Use of Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)
    Description ORR was defined as the percentage of participants, who had an objective response. Objective response was defined as either a complete response (CR) or partial response (PR) as determined by the investigator with use of Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). Objective response in this study did not need to be a confirmed response. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. ORR=CR+PR
    Time Frame Up to approximately 25 months after first participant enrolled

    Outcome Measure Data

    Analysis Population Description
    ORR analyses was performed on all randomized patients who had measureable disease at baseline
    Arm/Group Title Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel) Atezolizumab IC2/3 Chemotherapy IC2/3 Atezolizumab IC1/2/3 Chemotherapy IC1/2/3 Atezolizumab
    Arm/Group Description Participants randomized to the chemotherapy arm received vinflunine, paclitaxel, or docetaxel per the investigators choice. Vinflunine 320 milligrams per square meter (mg/m^2), paclitaxel 175 mg/m^2, or docetaxel 75 mg/m^2 were administered intravenously on Day 1 of each 21-day cycle until disease progression per standard RECIST v1.1 or unacceptable toxicity. Atezolizumab was administered intravenously at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle. Participants received atezolizumab as long as they continued to experience clinical benefit in the opinion of the investigator until unacceptable toxicity or symptomatic deterioration attributed to disease progression as determined by the investigator. PD-L1 immunohistochemistry (IHC) score of IC2/3 PD-L1 immunohistochemistry (IHC) score of IC2/3 PD-L1 immunohistochemistry (IHC) score of IC1/2/3 PD-L1 immunohistochemistry (IHC) score of IC1/2/3
    Measure Participants 461 462 116 113 306 312
    Number (95% Confidence Interval) [Percentage of participants]
    20.8
    4.5%
    15.4
    3.3%
    29.3
    3.1%
    26.5
    NaN
    22.2
    NaN
    16.3
    NaN
    8. Secondary Outcome
    Title Maximum Observed Serum Atezolizumab Concentration (Cmax)
    Description Cmax was measured for all participants that received at least one dose of Atezolizumab.
    Time Frame 30 minutes post dose on Day 1 of Cycles 1

    Outcome Measure Data

    Analysis Population Description
    The PK-evaluable population is defined as patients who received atezolizumab treatment and had at least one measureable PK concentration.
    Arm/Group Title Atezolizumab
    Arm/Group Description Atezolizumab was administered intravenously at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle. Participants received atezolizumab as long as they continued to experience clinical benefit in the opinion of the investigator until unacceptable toxicity or symptomatic deterioration attributed to disease progression as determined by the investigator.
    Measure Participants 467
    Geometric Mean (Standard Deviation) [mcg/mL]
    334
    (125)
    9. Secondary Outcome
    Title Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) Score: Global Health Status Scale
    Description The EORTC QLQ-C30 includes five functional scales (physical, role, cognitive, emotional, social); a global health status (GHS)/quality of life (QoL) scale; and items measuring fatigue, pain, nausea and vomiting, dyspnea, appetite loss, sleep disturbance, constipation, diarrhea, and financial difficulties. The score range for each scale and single-item measure is 0 to 100, where higher scores indicate a higher response level (i.e., better functioning, better QoL, worse symptoms). Key scales included physical functioning, and fatigue, and GHS.
    Time Frame Cycle 1 Day 1 (prior to any health care interaction), on Day 1 of each subsequent cycle, and at 30 days after the last treatment dose (Up to approximately 25 months; each cycle is 21 days)

    Outcome Measure Data

    Analysis Population Description
    All randomized patients with non-missing baseline assessment and at least one non-missing post-baseline assessment.
    Arm/Group Title Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel) Atezolizumab
    Arm/Group Description Participants randomized to the chemotherapy arm received vinflunine, paclitaxel, or docetaxel per the investigators choice. Vinflunine 320 milligrams per square meter (mg/m^2), paclitaxel 175 mg/m^2, or docetaxel 75 mg/m^2 were administered intravenously on Day 1 of each 21-day cycle until disease progression per standard RECIST v1.1 or unacceptable toxicity. Atezolizumab was administered intravenously at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle. Participants received atezolizumab as long as they continued to experience clinical benefit in the opinion of the investigator until unacceptable toxicity or symptomatic deterioration attributed to disease progression as determined by the investigator.
    Measure Participants 381 408
    Baseline (Cycle 1, Day 1)
    61.49
    (22.30)
    64.19
    (21.72)
    Change from baseline: Cycle 2, Day 1
    -5.47
    (20.02)
    -6.18
    (20.07)
    Change from baseline: Cycle 3, Day 1
    -3.76
    (22.34)
    -4.67
    (20.89)
    Change from baseline: Cycle 4, Day 1
    -1.48
    (19.71)
    -0.53
    (20.23)
    Change from baseline: Cycle 12, Day 1
    -3.95
    (24.33)
    -0.56
    (22.31)
    Change from baseline: Cycle 20, Day 1
    -2.27
    (16.28)
    1.10
    (21.88)
    Change from baseline: Cycle 28, Day 1
    -11.67
    (7.45)
    -5.26
    (33.82)
    Change from baseline:Treatment Discont. Visit
    -10.77
    (24.15)
    -16.71
    (24.39)
    10. Secondary Outcome
    Title Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) Score: Physical Functioning Scale
    Description The EORTC QLQ-C30 includes five functional scales (physical, role, cognitive, emotional, social); a global health status (GHS)/quality of life (QoL) scale; and items measuring fatigue, pain, nausea and vomiting, dyspnea, appetite loss, sleep disturbance, constipation, diarrhea, and financial difficulties. The score range for each scale and single-item measure is 0 to 100, where higher scores indicate a higher response level (i.e., better functioning, better QoL, worse symptoms). Key scales included physical functioning, and fatigue, and GHS.
    Time Frame Cycle 1 Day 1 (prior to any health care interaction), on Day 1 of each subsequent cycle, and at 30 days after the last treatment dose (Up to approximately 25 months; each cycle is 21 days)

    Outcome Measure Data

    Analysis Population Description
    All randomized patients with non-missing baseline assessment and at least one non-missing post-baseline assessment.
    Arm/Group Title Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel) Atezolizumab
    Arm/Group Description Participants randomized to the chemotherapy arm received vinflunine, paclitaxel, or docetaxel per the investigators choice. Vinflunine 320 milligrams per square meter (mg/m^2), paclitaxel 175 mg/m^2, or docetaxel 75 mg/m^2 were administered intravenously on Day 1 of each 21-day cycle until disease progression per standard RECIST v1.1 or unacceptable toxicity. Atezolizumab was administered intravenously at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle. Participants received atezolizumab as long as they continued to experience clinical benefit in the opinion of the investigator until unacceptable toxicity or symptomatic deterioration attributed to disease progression as determined by the investigator.
    Measure Participants 381 408
    Baseline (Cycle 1, Day 1)
    74.23
    (22.55)
    76.37
    (19.66)
    Change from baseline: Cycle 2, Day 1
    -4.80
    (15.70)
    -7.56
    (18.24)
    Change from baseline: Cycle 3, Day 1
    -5.64
    (17.37)
    -7.06
    (19.62)
    Change from baseline: Cycle 4, Day 1
    -4.41
    (16.25)
    -3.81
    (17.49)
    Change from baseline: Cycle 12, Day 1
    -6.97
    (20.20)
    0.89
    (16.23)
    Change from baseline: Cycle 20, Day 1
    -3.03
    (11.30)
    3.48
    (13.56)
    Change from baseline: Cycle 28, Day 1
    -18.67
    (24.68)
    3.51
    (20.53)
    Change from baseline: Treatment Discont. Visit
    -15.58
    (25.67)
    -20.19
    (25.52)
    11. Secondary Outcome
    Title Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) Score: Fatigue Symptom Scale
    Description The EORTC QLQ-C30 includes five functional scales (physical, role, cognitive, emotional, social); a global health status (GHS)/quality of life (QoL) scale; and items measuring fatigue, pain, nausea and vomiting, dyspnea, appetite loss, sleep disturbance, constipation, diarrhea, and financial difficulties. The score range for each scale and single-item measure is 0 to 100, where higher scores indicate a higher response level (i.e., better functioning, better QoL, worse symptoms). Key scales included physical functioning, and fatigue, and GHS.
    Time Frame Cycle 1 Day 1 (prior to any health care interaction), on Day 1 of each subsequent cycle, and at 30 days after the last treatment dose (Up to approximately 25 months; each cycle is 21 days)

    Outcome Measure Data

    Analysis Population Description
    All randomized patients with non-missing baseline assessment and at least one non-missing post-baseline assessment.
    Arm/Group Title Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel) Atezolizumab
    Arm/Group Description Participants randomized to the chemotherapy arm received vinflunine, paclitaxel, or docetaxel per the investigators choice. Vinflunine 320 milligrams per square meter (mg/m^2), paclitaxel 175 mg/m^2, or docetaxel 75 mg/m^2 were administered intravenously on Day 1 of each 21-day cycle until disease progression per standard RECIST v1.1 or unacceptable toxicity. Atezolizumab was administered intravenously at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle. Participants received atezolizumab as long as they continued to experience clinical benefit in the opinion of the investigator until unacceptable toxicity or symptomatic deterioration attributed to disease progression as determined by the investigator.
    Measure Participants 381 408
    Fatigue Symptom: Baseline (Cycle 1, Day 1)
    34.67
    (26.66)
    32.87
    (23.88)
    Fatigue Symptom: Cycle 2, Day 1
    10.71
    (23.13)
    10.56
    (21.82)
    Change from baseline: Cycle 3, Day 1
    11.04
    (25.48)
    9.41
    (24.80)
    Change from baseline: Cycle 4, Day 1
    7.48
    (22.63)
    3.67
    (23.57)
    Change from baseline: Cycle 12, Day 1
    5.70
    (27.44)
    -0.95
    (23.27)
    Change from baseline: Cycle 20, Day 1
    11.11
    (28.97)
    -8.05
    (21.97)
    Change from baseline: Cycle 28, Day 1
    15.56
    (16.85)
    -12.28
    (28.42)
    Change from baseline: Treatment Discont. Visit
    17.27
    (28.15)
    19.60
    (25.95)

    Adverse Events

    Time Frame From the first study drug to the data cutoff date: 8 Nov 2018 (up to 46 months)
    Adverse Event Reporting Description
    Arm/Group Title Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel) Atezolizumab
    Arm/Group Description Participants randomized to the chemotherapy arm will receive vinflunine, paclitaxel, or docetaxel per the investigator's choice. Vinflunine 320 milligrams per square meter (mg/m^2), paclitaxel 175 mg/m^2, or docetaxel 75 mg/m^2 will be administered intravenously on Day 1 of each 21-day cycle until disease progression per standard RECIST v1.1 or unacceptable toxicity. Atezolizumab was administered intravenously at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle. Participants received atezolizumab as long as they continued to experience clinical benefit in the opinion of the investigator until unacceptable toxicity or symptomatic deterioration attributed to disease progression as determined by the investigator.
    All Cause Mortality
    Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel) Atezolizumab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 393/443 (88.7%) 379/459 (82.6%)
    Serious Adverse Events
    Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel) Atezolizumab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 189/443 (42.7%) 192/459 (41.8%)
    Blood and lymphatic system disorders
    Anemia 5/443 (1.1%) 5 9/459 (2%) 9
    Bone Marrow Failure 2/443 (0.5%) 2 0/459 (0%) 0
    Febrile Neutropenia 22/443 (5%) 25 1/459 (0.2%) 1
    Neutropenia 14/443 (3.2%) 15 0/459 (0%) 0
    Thrombocytopenia 1/443 (0.2%) 1 2/459 (0.4%) 2
    Cardiac disorders
    Acute Coronary Syndrome 2/443 (0.5%) 2 0/459 (0%) 0
    Acute Myocardial Infarction 0/443 (0%) 0 2/459 (0.4%) 2
    Angina Pectoris 1/443 (0.2%) 1 0/459 (0%) 0
    Atrial Fibrillation 0/443 (0%) 0 1/459 (0.2%) 1
    Atrioventricular Block 1/443 (0.2%) 1 0/459 (0%) 0
    Cardiac Arrest 0/443 (0%) 0 2/459 (0.4%) 2
    Cardio-Respiratory Arrest 1/443 (0.2%) 1 0/459 (0%) 0
    Myocardial Infarction 0/443 (0%) 0 1/459 (0.2%) 1
    Pericardial Effusion 0/443 (0%) 0 2/459 (0.4%) 2
    Endocrine disorders
    Hyperthyroidism 0/443 (0%) 0 1/459 (0.2%) 1
    Hypothyroidism 0/443 (0%) 0 2/459 (0.4%) 2
    Adrenal Insufficiency 0/443 (0%) 0 1/459 (0.2%) 1
    Eye disorders
    Cataract 1/443 (0.2%) 1 1/459 (0.2%) 2
    Macular Fibrosis 0/443 (0%) 0 1/459 (0.2%) 1
    Papilloedema 1/443 (0.2%) 1 0/459 (0%) 0
    Visual Impairment 0/443 (0%) 0 1/459 (0.2%) 1
    Gastrointestinal disorders
    Abdominal Pain 9/443 (2%) 9 5/459 (1.1%) 5
    Abdominal Pain Lower 0/443 (0%) 0 3/459 (0.7%) 3
    Anal Haemorrhage 0/443 (0%) 0 2/459 (0.4%) 2
    Ascites 1/443 (0.2%) 1 0/459 (0%) 0
    Autoimmune Colitis 0/443 (0%) 0 1/459 (0.2%) 1
    Colitis 0/443 (0%) 0 3/459 (0.7%) 3
    Colitis Ulcerative 0/443 (0%) 0 2/459 (0.4%) 2
    Constipation 20/443 (4.5%) 23 2/459 (0.4%) 2
    Diarrhoea 3/443 (0.7%) 3 6/459 (1.3%) 6
    Duodenal Obstruction 0/443 (0%) 0 1/459 (0.2%) 1
    Enteritis 0/443 (0%) 0 2/459 (0.4%) 2
    Enterocolitis 1/443 (0.2%) 1 0/459 (0%) 0
    Enterovesical Fistula 0/443 (0%) 0 1/459 (0.2%) 1
    Gastric Haemorrhage 1/443 (0.2%) 1 0/459 (0%) 0
    Gastrointestinal Haemorrhage 1/443 (0.2%) 1 0/459 (0%) 0
    Ileal Perforation 0/443 (0%) 0 1/459 (0.2%) 1
    Ileus 6/443 (1.4%) 6 1/459 (0.2%) 2
    Inguinal Hernia 1/443 (0.2%) 1 0/459 (0%) 0
    Intestinal Obstruction 2/443 (0.5%) 2 2/459 (0.4%) 2
    Intestinal Perforation 0/443 (0%) 0 1/459 (0.2%) 1
    Jejunal Perforation 1/443 (0.2%) 1 0/459 (0%) 0
    Large Intestinal Obstruction 2/443 (0.5%) 2 2/459 (0.4%) 2
    Nausea 4/443 (0.9%) 4 0/459 (0%) 0
    Pancreatitis 0/443 (0%) 0 3/459 (0.7%) 3
    Rectal Haemorrhage 0/443 (0%) 0 1/459 (0.2%) 1
    Small Intestinal Obstruction 4/443 (0.9%) 4 1/459 (0.2%) 1
    Subileus 4/443 (0.9%) 4 2/459 (0.4%) 3
    Vomiting 2/443 (0.5%) 2 4/459 (0.9%) 5
    Dysphagia 0/443 (0%) 0 1/459 (0.2%) 1
    Enterocolitis Haemorrhagic 0/443 (0%) 0 1/459 (0.2%) 1
    Gastrointestinal Disorder 0/443 (0%) 0 1/459 (0.2%) 1
    General disorders
    Death 2/443 (0.5%) 2 3/459 (0.7%) 3
    Fatigue 5/443 (1.1%) 6 4/459 (0.9%) 4
    General Physical Health Deterioration 4/443 (0.9%) 4 2/459 (0.4%) 2
    Influenza Like Illness 0/443 (0%) 0 1/459 (0.2%) 1
    Injection Site Reaction 1/443 (0.2%) 1 0/459 (0%) 0
    Malaise 2/443 (0.5%) 2 1/459 (0.2%) 1
    Multiple Organ Dysfunction Syndrome 2/443 (0.5%) 2 0/459 (0%) 0
    Non-Cardiac Chest Pain 1/443 (0.2%) 1 0/459 (0%) 0
    Obstruction 1/443 (0.2%) 1 0/459 (0%) 0
    Oedema 0/443 (0%) 0 1/459 (0.2%) 1
    Oedema Peripheral 0/443 (0%) 0 1/459 (0.2%) 1
    Pain 4/443 (0.9%) 4 3/459 (0.7%) 3
    Peripheral Swelling 0/443 (0%) 0 1/459 (0.2%) 1
    Pyrexia 5/443 (1.1%) 5 17/459 (3.7%) 18
    Strangulated Hernia 1/443 (0.2%) 1 1/459 (0.2%) 1
    Asthenia 0/443 (0%) 0 2/459 (0.4%) 2
    Unevaluable Event 0/443 (0%) 0 1/459 (0.2%) 1
    Hepatobiliary disorders
    Autoimmune Hepatitis 0/443 (0%) 0 4/459 (0.9%) 5
    Biliary Dilation 1/443 (0.2%) 1 0/459 (0%) 0
    Cholecystitis 0/443 (0%) 0 2/459 (0.4%) 2
    Hepatocellular Injury 0/443 (0%) 0 1/459 (0.2%) 1
    Hyperbilirubinaemia 0/443 (0%) 0 1/459 (0.2%) 1
    Jaundice 1/443 (0.2%) 1 0/459 (0%) 0
    Portal Vein Thrombosis 0/443 (0%) 0 1/459 (0.2%) 1
    Immune system disorders
    Drug Hypersensitivity 0/443 (0%) 0 1/459 (0.2%) 1
    Hypersensitivity 0/443 (0%) 0 1/459 (0.2%) 1
    Infections and infestations
    Arthritis Infective 1/443 (0.2%) 1 0/459 (0%) 0
    Bacteraemia 1/443 (0.2%) 1 0/459 (0%) 0
    Bacterial Infection 0/443 (0%) 0 1/459 (0.2%) 1
    Bronchitis 1/443 (0.2%) 1 0/459 (0%) 0
    Cystitis 0/443 (0%) 0 1/459 (0.2%) 1
    Device Related Infection 0/443 (0%) 0 2/459 (0.4%) 2
    Enterococcal Infection 1/443 (0.2%) 2 0/459 (0%) 0
    Enterococcal Sepsis 0/443 (0%) 0 1/459 (0.2%) 1
    Erysipelas 1/443 (0.2%) 1 1/459 (0.2%) 3
    Escherichia Infection 0/443 (0%) 0 1/459 (0.2%) 1
    Escherichia Pyelonephritis 0/443 (0%) 0 1/459 (0.2%) 1
    Escherichia Sepsis 1/443 (0.2%) 1 1/459 (0.2%) 1
    Gastroenteritis 1/443 (0.2%) 1 0/459 (0%) 0
    Infection 3/443 (0.7%) 3 1/459 (0.2%) 1
    Kidney Infection 1/443 (0.2%) 1 0/459 (0%) 0
    Klebsiella Infection 0/443 (0%) 0 2/459 (0.4%) 2
    Lower Respiratory Tract Infection 0/443 (0%) 0 1/459 (0.2%) 1
    Lung Infection 0/443 (0%) 0 2/459 (0.4%) 2
    Meningoencephalitis Viral 0/443 (0%) 0 1/459 (0.2%) 1
    Neutropenic Infection 1/443 (0.2%) 1 0/459 (0%) 0
    Neutropenic Sepsis 2/443 (0.5%) 2 0/459 (0%) 0
    Ophthalmic Herpes Zoster 0/443 (0%) 0 1/459 (0.2%) 1
    Peritonitis 0/443 (0%) 0 1/459 (0.2%) 1
    Pneumonia 7/443 (1.6%) 7 4/459 (0.9%) 5
    Pyelonephritis 0/443 (0%) 0 1/459 (0.2%) 1
    Respiratory Tract Infection 1/443 (0.2%) 1 3/459 (0.7%) 3
    Sepsis 15/443 (3.4%) 16 8/459 (1.7%) 8
    Septic Shock 2/443 (0.5%) 2 2/459 (0.4%) 2
    Spinal Cord Infection 0/443 (0%) 0 1/459 (0.2%) 1
    Staphylococcal Infection 0/443 (0%) 0 1/459 (0.2%) 1
    Toxic Shock Syndrome 1/443 (0.2%) 1 0/459 (0%) 0
    Urinary Tract Infection 14/443 (3.2%) 17 21/459 (4.6%) 25
    Urinary Tract Infection Bacterial 1/443 (0.2%) 1 0/459 (0%) 0
    Urosepsis 12/443 (2.7%) 12 2/459 (0.4%) 2
    Escherichia Bacteraemia 0/443 (0%) 0 1/459 (0.2%) 1
    Influenza 0/443 (0%) 0 1/459 (0.2%) 1
    Pyonephrosis 0/443 (0%) 0 1/459 (0.2%) 1
    Vascular Device Infection 4/443 (0.9%) 4 0/459 (0%) 0
    Injury, poisoning and procedural complications
    Compression Fracture 0/443 (0%) 0 1/459 (0.2%) 1
    Femoral Neck Fracture 1/443 (0.2%) 1 0/459 (0%) 0
    Infusion Related Reaction 0/443 (0%) 0 2/459 (0.4%) 2
    Lower Limb Fracture 0/443 (0%) 0 1/459 (0.2%) 1
    Lumbar Vertebral Fracture 1/443 (0.2%) 1 0/459 (0%) 0
    Spinal Compression Fracture 1/443 (0.2%) 1 0/459 (0%) 0
    Stoma Site Haemorrhage 0/443 (0%) 0 1/459 (0.2%) 1
    Toxicity to Various Agents 1/443 (0.2%) 1 1/459 (0.2%) 1
    Urostomy Complication 1/443 (0.2%) 1 0/459 (0%) 0
    Skin Injury 0/443 (0%) 0 1/459 (0.2%) 1
    Investigations
    Alanine Aminotransferase Increased 0/443 (0%) 0 2/459 (0.4%) 2
    Aspartate Aminotransferase Increased 0/443 (0%) 0 1/459 (0.2%) 1
    Blood Bilirubin Increased 1/443 (0.2%) 1 2/459 (0.4%) 2
    Blood Creatinine Increased 1/443 (0.2%) 1 1/459 (0.2%) 1
    Liver Function Test Abnormal 0/443 (0%) 0 1/459 (0.2%) 1
    Neutrophil Count Decreased 4/443 (0.9%) 4 0/459 (0%) 0
    Platelet Count Decreased 1/443 (0.2%) 1 0/459 (0%) 0
    Transaminases Increased 0/443 (0%) 0 1/459 (0.2%) 1
    White Blood Cell Count Decreased 1/443 (0.2%) 1 0/459 (0%) 0
    Gamma-Glutamyltransferase Increased 0/443 (0%) 0 1/459 (0.2%) 1
    Metabolism and nutrition disorders
    Decreased Appetite 0/443 (0%) 0 1/459 (0.2%) 1
    Dehydration 3/443 (0.7%) 4 2/459 (0.4%) 2
    Diabetes Mellitus 0/443 (0%) 0 1/459 (0.2%) 1
    Diabetic Ketoacidosis 0/443 (0%) 0 1/459 (0.2%) 1
    Failure to Thrive 0/443 (0%) 0 1/459 (0.2%) 1
    Hypercalcaemia 1/443 (0.2%) 1 3/459 (0.7%) 3
    Hyperkalaemia 0/443 (0%) 0 1/459 (0.2%) 1
    Hyperglycaemia 0/443 (0%) 0 1/459 (0.2%) 2
    Hypokalaemia 1/443 (0.2%) 1 1/459 (0.2%) 1
    Hyponatraemia 3/443 (0.7%) 3 4/459 (0.9%) 4
    Hypoglycaemia 0/443 (0%) 0 1/459 (0.2%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/443 (0.2%) 1 1/459 (0.2%) 1
    Back Pain 4/443 (0.9%) 4 6/459 (1.3%) 6
    Bone Pain 3/443 (0.7%) 3 1/459 (0.2%) 1
    Groin Pain 0/443 (0%) 0 1/459 (0.2%) 1
    Myalgia 1/443 (0.2%) 1 0/459 (0%) 0
    Myositis 0/443 (0%) 0 1/459 (0.2%) 1
    Pain in Extremity 1/443 (0.2%) 1 1/459 (0.2%) 1
    Pathological Fracture 1/443 (0.2%) 1 0/459 (0%) 0
    Rhabdomyolysis 0/443 (0%) 0 1/459 (0.2%) 1
    Arthritis 0/443 (0%) 0 1/459 (0.2%) 1
    Gouty Arthritis 0/443 (0%) 0 1/459 (0.2%) 1
    Osteoarthritis 0/443 (0%) 0 1/459 (0.2%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Colon Cancer 0/443 (0%) 0 1/459 (0.2%) 1
    Mantle Cell Lymphoma 0/443 (0%) 0 1/459 (0.2%) 1
    Neoplasm Malignant 0/443 (0%) 0 1/459 (0.2%) 1
    Tumor Associated Fever 0/443 (0%) 0 1/459 (0.2%) 1
    Cancer Pain 0/443 (0%) 0 1/459 (0.2%) 1
    Gastric Cancer 0/443 (0%) 0 1/459 (0.2%) 1
    Nervous system disorders
    Brain Oedema 0/443 (0%) 0 1/459 (0.2%) 1
    Dizziness 0/443 (0%) 0 1/459 (0.2%) 1
    Dyskinesia 0/443 (0%) 0 1/459 (0.2%) 1
    Epilepsy 0/443 (0%) 0 1/459 (0.2%) 1
    Headache 1/443 (0.2%) 1 0/459 (0%) 0
    Ischaemic Stroke 0/443 (0%) 0 2/459 (0.4%) 2
    Leukoencephalopathy 1/443 (0.2%) 1 0/459 (0%) 0
    Radiculopathy 1/443 (0.2%) 1 0/459 (0%) 0
    Sciatica 0/443 (0%) 0 1/459 (0.2%) 1
    Syncope 0/443 (0%) 0 2/459 (0.4%) 2
    Transient Ischaemic Attack 0/443 (0%) 0 1/459 (0.2%) 1
    Parkinson's Disease 0/443 (0%) 0 1/459 (0.2%) 1
    Product Issues
    Device Dislocation 1/443 (0.2%) 1 0/459 (0%) 0
    Device Occlusion 3/443 (0.7%) 5 1/459 (0.2%) 2
    Psychiatric disorders
    Completed Suicide 0/443 (0%) 0 1/459 (0.2%) 1
    Confusional State 1/443 (0.2%) 1 0/459 (0%) 0
    Renal and urinary disorders
    Acute Kidney Injury 6/443 (1.4%) 6 11/459 (2.4%) 12
    Anuria 0/443 (0%) 0 1/459 (0.2%) 1
    Bladder Perforation 1/443 (0.2%) 1 0/459 (0%) 0
    Bladder Tamponade 0/443 (0%) 0 1/459 (0.2%) 1
    Haematuria 7/443 (1.6%) 9 10/459 (2.2%) 19
    Hydronephrosis 0/443 (0%) 0 3/459 (0.7%) 3
    Postrenal Failure 0/443 (0%) 0 1/459 (0.2%) 1
    Renal Failure 5/443 (1.1%) 5 4/459 (0.9%) 4
    Renal Haematoma 0/443 (0%) 0 1/459 (0.2%) 1
    Urethral Haemorrhage 0/443 (0%) 0 1/459 (0.2%) 1
    Urinary Bladder Haemorrhage 0/443 (0%) 0 1/459 (0.2%) 1
    Urinary Retention 1/443 (0.2%) 1 6/459 (1.3%) 6
    Urinary Tract Obstruction 0/443 (0%) 0 1/459 (0.2%) 1
    Urinary Tract Pain 0/443 (0%) 0 1/459 (0.2%) 1
    Urinoma 1/443 (0.2%) 1 0/459 (0%) 0
    Reproductive system and breast disorders
    Vaginal Haemorrhage 0/443 (0%) 0 1/459 (0.2%) 1
    Genital Haemorrhage 0/443 (0%) 0 1/459 (0.2%) 1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 0/443 (0%) 0 7/459 (1.5%) 7
    Pleural Effusion 1/443 (0.2%) 1 2/459 (0.4%) 2
    Pneumonia Aspiration 1/443 (0.2%) 1 1/459 (0.2%) 1
    Pneumonitis 2/443 (0.5%) 2 4/459 (0.9%) 4
    Pneumothorax 0/443 (0%) 0 1/459 (0.2%) 1
    Productive Cough 0/443 (0%) 0 1/459 (0.2%) 1
    Pulmonary Embolism 2/443 (0.5%) 2 4/459 (0.9%) 4
    Respiratory Distress 0/443 (0%) 0 1/459 (0.2%) 1
    Respiratory Failure 0/443 (0%) 0 2/459 (0.4%) 2
    Haemoptysis 0/443 (0%) 0 1/459 (0.2%) 1
    Skin and subcutaneous tissue disorders
    Psoriasis 0/443 (0%) 0 1/459 (0.2%) 1
    Toxic Epidermal Necrolysis 0/443 (0%) 0 1/459 (0.2%) 1
    Vascular disorders
    Deep Vein Thrombosis 2/443 (0.5%) 2 4/459 (0.9%) 4
    Embolism 0/443 (0%) 0 1/459 (0.2%) 1
    Hypertension 2/443 (0.5%) 2 0/459 (0%) 0
    Thrombophlebitis 3/443 (0.7%) 3 0/459 (0%) 0
    Thrombosis 1/443 (0.2%) 1 0/459 (0%) 0
    Internal Haemorrhage 1/443 (0.2%) 1 0/459 (0%) 0
    Other (Not Including Serious) Adverse Events
    Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel) Atezolizumab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 417/443 (94.1%) 413/459 (90%)
    Blood and lymphatic system disorders
    Anaemia 124/443 (28%) 142 90/459 (19.6%) 94
    Neutropenia 57/443 (12.9%) 75 5/459 (1.1%) 6
    Gastrointestinal disorders
    Abdominal Pain 58/443 (13.1%) 63 52/459 (11.3%) 60
    Abdominal Pain Upper 27/443 (6.1%) 32 23/459 (5%) 23
    Constipation 163/443 (36.8%) 221 131/459 (28.5%) 147
    Diarrhoea 94/443 (21.2%) 115 97/459 (21.1%) 145
    Dry Mouth 8/443 (1.8%) 8 30/459 (6.5%) 36
    Nausea 137/443 (30.9%) 171 106/459 (23.1%) 124
    Stomatitis 35/443 (7.9%) 41 13/459 (2.8%) 16
    Vomiting 81/443 (18.3%) 108 55/459 (12%) 67
    General disorders
    Asthenia 107/443 (24.2%) 144 92/459 (20%) 108
    Fatigue 136/443 (30.7%) 162 129/459 (28.1%) 153
    Mucosal Inflammation 47/443 (10.6%) 64 27/459 (5.9%) 30
    Oedema Peripheral 36/443 (8.1%) 43 52/459 (11.3%) 59
    Pain 31/443 (7%) 34 24/459 (5.2%) 24
    Pyrexia 62/443 (14%) 76 93/459 (20.3%) 128
    Infections and infestations
    Nasopharyngitis 11/443 (2.5%) 15 27/459 (5.9%) 43
    Urinary Tract Infection 58/443 (13.1%) 76 84/459 (18.3%) 141
    Investigations
    Blood Creatinine Increased 11/443 (2.5%) 12 36/459 (7.8%) 38
    Neutrophil Count Decreased 26/443 (5.9%) 49 0/459 (0%) 0
    Weight Decreased 45/443 (10.2%) 46 47/459 (10.2%) 47
    Metabolism and nutrition disorders
    Decreased Appetite 113/443 (25.5%) 136 135/459 (29.4%) 147
    Hypokalaemia 23/443 (5.2%) 26 16/459 (3.5%) 17
    Musculoskeletal and connective tissue disorders
    Arthralgia 60/443 (13.5%) 79 47/459 (10.2%) 66
    Back Pain 51/443 (11.5%) 53 80/459 (17.4%) 95
    Bone Pain 24/443 (5.4%) 28 24/459 (5.2%) 27
    Myalgia 55/443 (12.4%) 68 25/459 (5.4%) 27
    Pain in Extremity 48/443 (10.8%) 55 37/459 (8.1%) 46
    Nervous system disorders
    Dizziness 30/443 (6.8%) 32 29/459 (6.3%) 29
    Dysgeusia 25/443 (5.6%) 27 12/459 (2.6%) 14
    Headache 26/443 (5.9%) 35 38/459 (8.3%) 44
    Neuropathy Peripheral 55/443 (12.4%) 67 8/459 (1.7%) 9
    Paraesthesia 29/443 (6.5%) 32 18/459 (3.9%) 18
    Peripheral Sensory Neuropathy 41/443 (9.3%) 43 6/459 (1.3%) 7
    Psychiatric disorders
    Anxiety 24/443 (5.4%) 24 27/459 (5.9%) 27
    Insomnia 42/443 (9.5%) 42 45/459 (9.8%) 48
    Renal and urinary disorders
    Haematuria 26/443 (5.9%) 32 45/459 (9.8%) 60
    Respiratory, thoracic and mediastinal disorders
    Cough 30/443 (6.8%) 36 59/459 (12.9%) 69
    Dyspnoea 46/443 (10.4%) 50 62/459 (13.5%) 70
    Skin and subcutaneous tissue disorders
    Alopecia 125/443 (28.2%) 127 1/459 (0.2%) 1
    Pruritus 19/443 (4.3%) 27 64/459 (13.9%) 86
    Rash 28/443 (6.3%) 37 54/459 (11.8%) 72
    Vascular disorders
    Hypertension 20/443 (4.5%) 22 23/459 (5%) 24

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

    Results Point of Contact

    Name/Title Medical Communications
    Organization Hoffmann-La Roche
    Phone 800-821-8590
    Email genentech@druginfo.com
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT02302807
    Other Study ID Numbers:
    • GO29294
    • 2014-003231-19
    First Posted:
    Nov 27, 2014
    Last Update Posted:
    Aug 1, 2019
    Last Verified:
    Jul 1, 2019