Clinical trial NCT03191786: A Study of Atezolizumab Compared With a Single-Agent Chemotherapy in Treatment Naïve Participants With Locally Advanced or Recurrent or Metastatic Non-Small Cell Lung Cancer Who Are Deemed Unsuitable For Platinum-Doublet Chemotherapy
Official title: A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab Compared With Chemotherapy in Patients With Treatment Naïve Advanced or Recurrent (Stage IIIb Not Amenable for Multimodality Treatment) or Metastatic (Stage IV) Non-Small Cell Lung Cancer Who Are Deemed Unsuitable for Platinum-Containing Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-Small Cell Lung Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2017-06-19
Enrollment: 453
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This Phase III, global, multicenter, open-label, randomized, controlled study will evaluate the efficacy and safety of atezolizumab (an anti-programmed death-ligand 1 \[anti-PD-L1\] antibody) compared with a single agent chemotherapy regimen by investigator choice (vinorelbine or gemcitabine) in treatment-naïve participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) who are deemed unsuitable for any platinum-doublet chemotherapy due to poor performance status (Eastern Cooperative Oncology Group \[ECOG\] performance status of 2-3).


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC as per the American Joint Committee on Cancer (AJCC) 7th edition
* No sensitizing epidermal growth factor receptor (EGFR) mutation (L858R or exon 19 deletions) or anaplastic lymphoma kinase (ALK) fusion oncogene detected
* No prior systemic treatment for advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC as per the AJCC 7th edition
* Life expectancy greater than or equal to (\>/=) 8 weeks
* Deemed unsuitable by the investigator for any platinum-doublet chemotherapy due to poor performance status (ECOG performance status of 2-3). However, participants \>= 70 years of age who have an ECOG PS of 0 or 1 may be included due to: a) substantial comorbidities; b) contraindication(s) for any platinum-doublet chemotherapy
* Representative formalin-fixed paraffin-embedded (FPPE) tumor tissue block obtained during course of disease (archival tissue) or at screening
* Participants with treated, asymptomatic central nervous system (CNS) metastases are eligible, provided they meet all of the following criteria: Measurable disease outside CNS; Only supratentorial and cerebellar metastases allowed; No ongoing requirement for corticosteroids as therapy for CNS disease; No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to randomization; No evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study
* Adequate hematologic and end organ function
* Female participants of childbearing potential randomized to the atezolizumab treatment arm agree to use protocol defined methods of contraception

Exclusion Criteria:

Cancer-Specific Exclusion Criteria:

* Participants younger than 70 years who have an ECOG performance status of 0 or 1
* Active or untreated CNS metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation of the brain during screening and prior radiographic assessments
* Uncontrolled tumor-related pain
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
* Uncontrolled or symptomatic hyerpcalcemia (ionized calcium \> 1.5 mmol/L or calcium \>12 mg/dL or corrected serum calcium \>ULN)
* History of other malignancy within 5 years prior to screening, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
* National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 (v4.0) Grade 3 or higher toxicities due to any prior therapy (example \[e.g.\], radiotherapy) (excluding alopecia), which have not shown improvement and are strictly considered to interfere with current study medication
* Participants who have received prior neo-adjuvant, adjuvant chemotherapy, radiotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from randomization since the last chemotherapy, radiotherapy, or chemoradiotherapy

General Medical Exclusion Criteria:

* History of autoimmune disease except autoimmune-related hypothyroidism and controlled Type I diabetes mellitus
* History of idiopathic pulmonary fibrosis (IPF), organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis
* Known positivity for human immunodeficiency virus (HIV)
* Known active hepatitis B or hepatitis C
* Active tuberculosis
* Severe infections within 4 weeks prior to randomization
* Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (Class II or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina
* Major surgical procedure other than for diagnosis within 4 weeks prior to randomization or anticipation of need for a major surgical procedure during the course of the study
* Prior allogeneic bone marrow transplantation or solid organ transplant
* Participants with an illness or condition that may interfere with capacity or compliance with the study protocol, as per investigator's judgment
* Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days prior to randomization

Exclusion Criteria Related to Atezolizumab:

* 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
* Oral or IV antibiotic treatment
* Administration of a live, attenuated vaccine within 4 weeks before randomization or anticipation that such a live attenuated vaccine will be required during the study
* Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibodies
* Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to randomization
* Treatment with systemic corticosteroids or other immunosuppressive medications
* Participants not willing to stop treatment with traditional herbal medicines

Exclusion Criteria Related to Chemotherapy:

* Known sensitivity and contraindications to the 2 comparative chemotherapy agents (that is \[i.e.\] vinorelbine, oral or intravenous, and gemcitabine, intravenous)

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization up to death from any cause (up to approximately 55 months)
Secondary outcomes:
measure: OS Rates at the 6, 12, 18, 24-Months Timepoints
timeFrame: 6, 12, 18 and 24 months
measure: Percentage of Participants With Objective Response, as Determined by the Investigator Using Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)
timeFrame: From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months)
measure: Progression-Free Survival (PFS), as Determined by the Investigator Using RECIST v1.1
timeFrame: From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months)
measure: Duration of Response (DOR), as Determined by the Investigator Using RECIST v1.1
timeFrame: Time from the first occurrence of a documented objective response to the time of disease progression or death from any cause, whichever occurs first (up to approximately 55 months)
measure: Percentage of Participants With At Least One Adverse Event (AE)
timeFrame: Baseline up to 90 days after last dose of atezolizumab (approximately 62 months)
measure: Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC-QLQ-C30) Score
timeFrame: Baseline, Day 1 of each treatment cycle up to 30 days after last dose (up to approximately 55 months) (Cycle length = 21 days)
measure: Change From Baseline in EORTC QLQ Supplementary Lung Cancer Module 13 (EORTC QLQ-LC13) Score
timeFrame: Baseline, Day 1 of each treatment cycle up to 30 days after last dose (up to approximately 55 months) (Cycle length = 21 days)
measure: Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms as Assessed by EORTC QLQ-C30 Score
timeFrame: From baseline up to approximately 55 months
measure: TTD in Patient-Reported Lung Cancer Symptoms As Assessed by EORTC QLQ-LC13 Score
timeFrame: From baseline up to approximately 55 months
measure: OS in Participants With Programmed Death-Ligand 1 (PD-L1) Positive Status
timeFrame: From randomization up to death from any cause (up to approximately 55 months)
measure: PFS as Determined by the Investigator Using RECIST v1.1 in Participants With PD-L1 Positive Status
timeFrame: From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months)
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Fundación CENIT para la Investigación en Neurociencias
city: Mar del Plata
country: Argentina
facility: Hospital Privado de Comunidad
city: Viedma
country: Argentina
facility: Clinica Viedma S.A.
city: Brussel
country: Belgium
facility: UZ Brussel
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi Notre Dame
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceicao
state: RS
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas - PUCRS
state: RS
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo - ICESP
state: SP
city: Pleven
country: Bulgaria
facility: Umhat Dr Georgi Stranski; Clinic of Chemotherapy
city: Plovdiv
country: Bulgaria
facility: Complex Oncology Center (COC)-Plovidiv
city: Vancouver
country: Canada
facility: BCCA-Vancouver Cancer Centre
state: British Columbia
city: Moncton
country: Canada
facility: Regional health authority A vitalite health network
state: New Brunswick
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Changsha
country: China
facility: Hu Nan Provincial Cancer Hospital
city: Hangzhou City
country: China
facility: The Second Affiliated Hospital of Zhejiang University School of Medicine
city: Hefei
country: China
facility: Anhui Provincial Hospital
city: Shanghai
country: China
facility: Shanghai Chest Hospital
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
city: Wuhan
country: China
facility: Union Hospital of Tongji Medical College, Dept. of Cancer Center; Cancer Center
city: Bogota
country: Colombia
facility: Fundacion Cardioinfantil
city: Medellin
country: Colombia
facility: Fundación Centro de Investigación Clínica CIC
city: Monteria
country: Colombia
facility: Oncomedica S.A.
city: Pereira
country: Colombia
facility: Oncólogos de Occidente
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc; Pneumologicka klinika
city: Odense C
country: Denmark
facility: Odense Universitetshospital, Onkologisk Afdeling R
city: Berlin
country: Germany
facility: Evang. Lungenklinik Berlin Klinik für Pneumologie
city: Gauting
country: Germany
facility: Asklepios Klinik Gauting; Onkologisches Studienzentrum
city: Großhansdorf
country: Germany
facility: LungenClinic Großhansdorf GmbH; Klinische Forschung
city: Halle
country: Germany
facility: Krankenhaus Martha-Maria Halle-Doelau gGmbH; Klinik fuer Innere Medizin II
city: Immenhausen
country: Germany
facility: Fachklinik für Lungenerkrankungen
city: Marburg
country: Germany
facility: Klinikum der Philipps-Universität Marburg
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg; Klinik und Poliklinik für Innere Medizin II, Pneumologie
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen; Innere Medizin VIII, Medizinische Onkologie und Pneumologie
city: New Delhi
country: India
facility: Max Super Speciality Hospital
state: Delhi
city: New Delhi
country: India
facility: Indraprastha Apollo Hospitals
state: Delhi
city: New Delhi
country: India
facility: Rajiv Gandhi Cancer Inst.&Research Center; Medical Oncology
state: Delhi
city: Ahmedabad
country: India
facility: HealthCare Global Cancer Centre; Medical Oncology
state: Gujarat
city: Vadodara
country: India
facility: Kailash Cancer Hospital and Research Center
state: Gujarat
city: Mahim(West)
country: India
facility: P.D. Hinduja Nat. Hospital & Med. Research Centre
state: Maharashtra
city: Mumbai
country: India
facility: Tata Memorial Hospital; Dept of Medical Oncology
state: Maharashtra
city: Mumbai
country: India
facility: Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute; Department of Rheumatologz
state: Maharashtra
city: Nashik
country: India
facility: HCG Manavata Cancer Centre
state: Maharashtra
city: Pune
country: India
facility: Grant Medical Foundation, Ruby Hall Clinic
state: Maharashtra
city: Pune
country: India
facility: Deenanath Mangeshkar Hospital & Research Centre
state: Maharashtra
city: Hyderabad
country: India
facility: Indo-American Cancer Hospital & Research Center
state: Telangana
city: Kolkata
country: India
facility: Tata Medical Center; Department of Medical Oncology
state: WEST Bengal
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital - Institute for Cancer Research
city: Limerick
country: Ireland
facility: University Hospital Limerick - Clinical Trials Department
city: Ravenna
country: Italy
facility: Ospedale Provinciale Santa Maria Delle Croci; Oncologia Medica
state: Emilia-Romagna
city: Roma
country: Italy
facility: Azienda Ospedaliera San Camillo Forlanini; U.O.C. Pneumologia Ad Indirizzo Oncologico 1
state: Lazio
city: Monza MI
country: Italy
facility: Azienda Ospedaliera San Gerardo di Monza
state: Lombardia
city: Almaty
country: Kazakhstan
facility: Kazakh Scientific Research Institution Of Oncology and Radiology
city: Almaty
country: Kazakhstan
facility: Almaty Oncology Center
city: Luxembourg
country: Luxembourg
facility: Centre Hospitalier de Luxembourg
city: Cdmx
country: Mexico
facility: Health Pharma Professional Research
state: Mexico CITY (federal District)
city: San Luis Potosí
country: Mexico
facility: Oncologico Potosino
state: SAN LUIS Potosi
city: Chihuahua
country: Mexico
facility: Centro Estatal de Cancerologia de Chihuahua; ONCOLOGY
city: Otwock
country: Poland
facility: Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy; Oddzial Iii
city: Warszawa
country: Poland
facility: Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad; Klinika Nowot.Pluca i Klatki Piers
city: Coimbra
country: Portugal
facility: CHUC - Unidade de Pneumologia Oncológica; Hospital de Dia de Oncologia Edificio Sao Jeronimo
city: Porto
country: Portugal
facility: IPO do Porto; Servico de Oncologia Medica
city: Cluj Napoca
country: Romania
facility: Institutul Oncologic Prof. Dr. Ion Chiricuta Cluj Napoca; Oncologie Medicala
city: Floresti
country: Romania
facility: Centrul de Radioterapie AMETHYST
city: Timi?oara
country: Romania
facility: Oncocenter Timisoara
city: Nitra
country: Slovakia
facility: Specializovana nemocnica sv. Svorada Zobor, n.o.; Oddelenie klinickej onkologie
city: Trnava
country: Slovakia
facility: Fakultna nemocnica Trnava
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia
state: LA Coruña
city: Bilbao
country: Spain
facility: Hospital de Cruces; Servicio de Oncologia
state: Vizcaya
city: Barcelona
country: Spain
facility: Institut Catala d Oncologia Hospital Duran i Reynals
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario Clínico San Carlos; Servicio de Oncologia
city: Malaga
country: Spain
facility: Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia
city: Murcia
country: Spain
facility: Hospital General Universitario J.M Morales Meseguer; Servicio de Oncologia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena; Servicio de Oncologia
city: Valencia
country: Spain
facility: Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia
city: Bellinzona
country: Switzerland
facility: Ospedale Regionale di Bellinzona Medizin Onkologie
city: Thun
country: Switzerland
facility: Spital STS AG - Spital Thun Medizin Onkologie; MEDIZINISCHE KLINIK
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur; Medizinische Onkologie
city: Bebington
country: United Kingdom
facility: Clatterbridge Cancer Centre
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Cornwall
country: United Kingdom
facility: Royal Cornwall Hospital; Dept of Clinical Oncology
city: Glasgow
country: United Kingdom
facility: New Victoria Hospital
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust - University College Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital Nhs Trust; Medical Oncology
city: York
country: United Kingdom
facility: YORK DISTRICT HOSPITAL; Haematology/Oncology Department
city: Hanoi
country: Vietnam
facility: Bach Mai Hospital
city: Hochiminh city
country: Vietnam
facility: Cho Ray Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: