Clinical trial NCT02763579: A Study of Carboplatin Plus Etoposide With or Without Atezolizumab in Participants With Untreated Extensive-Stage (ES) Small Cell Lung Cancer (SCLC)
Official title: A Phase I/III, Randomized, Double-Blind, Placebo-Controlled Study of Carboplatin Plus Etoposide With or Without Atezolizumab (Anti-PD-L1 Antibody) in Patients With Untreated Extensive-Stage Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Small Cell Lung Carcinoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-05-05
Enrollment: 503
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 randomized, Phase I/III, multicenter, double-blinded, placebo-controlled study was designed to evaluate the safety and efficacy of atezolizumab (anti-programmed death-ligand 1 \[PD-L1\] antibody) in combination with carboplatin plus (+) etoposide compared with treatment with placebo + carboplatin + etoposide in chemotherapy-naive participants with ES-SCLC. Participants will be randomized in a 1:1 ratio to receive either atezolizumab + carboplatin + etoposide or placebo + carboplatin + etoposide on 21-day cycles for four cycles in the induction phase followed by maintenance with atezolizumab or placebo until progressive disease (PD) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Treatment can be continued until persistent radiographic PD or symptomatic deterioration.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration Lung Study Group \[VALG\] staging system)
* No prior systemic treatment for ES-SCLC
* Eastern Cooperative Oncology Group performance status of 0 or 1
* Measurable disease, as defined by RECIST v1.1
* Adequate hematologic and end organ function
* Treatment-free for at least 6 months since last chemo/radiotherapy, among those treated (with curative intent) with prior chemo/radiotherapy for limited-stage SCLC

Exclusion Criteria:

* Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation
* Malignancies other than SCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
* Pregnant or lactating women
* History of autoimmune disease
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
* Positive test result for human immunodeficiency virus (HIV)
* Active hepatitis B or hepatitis C
* Severe infections at the time of randomization
* Significant cardiovascular disease
* Prior treatment with cluster of differentiation (CD) 137 agonists or immune checkpoint blockade therapies, anti-programmed death-1 (PD-1), and anti-PD-L1 therapeutic antibody
* History of severe (or known) hypersensitivity to chimeric or humanized antibodies or fusion proteins or any component of atezolizumab formulation.

Primary outcomes:
measure: Duration of Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1 in the Global Population
timeFrame: Baseline until PD or death, whichever occurs first (up to approximately 23 months)
measure: Duration of Overall Survival (OS) in the Global Population
timeFrame: Baseline until death from any cause (up to approximately 23 months)
Secondary outcomes:
measure: Percentage of Participants With Objective Response Rate (ORR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population
timeFrame: Baseline until partial response (PR) or complete response (CR), whichever occurs first (up to approximately 23 months)
measure: Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population
timeFrame: First occurrence of PR or CR until PD or death, whichever occurs first (up to approximately 23 months)
measure: PFS Rate at 6 Months and at 1 Year in Global Population
timeFrame: 6 months, 1 year
measure: OS Rate at 1 Year and 2 Years in the Global Population
timeFrame: 1 year, 2 years
measure: Time to Deterioration (TTD) Per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core 30 (C30) and Supplemental Lung Cancer Module (QLQ-LC13) in the Global Population
timeFrame: Baseline until deterioration per symptom subscale (up to approximately 23 months)
measure: Percentage of Participants With at Least One Adverse Event in the Global Population
timeFrame: Baseline until up to 90 days after end of treatment (up to approximately 49 months)
measure: Percentage of Participants With Anti-Drug Antibodies (ADA) to Atezolizumab in the Global Population
timeFrame: Predose (0 hours [H]) on Day (D) 1 of Cycles (C) 1, 2, 3, 4, 8, 16, and every 8 cycles (Q8C) thereafter (cycle = 21 days) until treatment discontinuation (up to 23 months) and 120 days after last dose (up to approximately 23 months overall)
measure: Maximum Observed Serum Concentration (Cmax) of Atezolizumab in the Global Population
timeFrame: Post-dose Day 1 of Cycle 1 (cycle length = 21 days)
measure: Minimum Observed Serum Concentration (Cmin) of Atezolizumab in the Global Population
timeFrame: Predose on Day 1 of Cycles 1, 3, 4, 8, 16 and 24 (cycle length = 21 days)
measure: Plasma Concentration of Carboplatin in the Global Population
timeFrame: Predose, before end of infusion, and after end of carboplatin infusion on Day 1 of Cycle 1 and Cycle 3 (cycle = 21 days)
measure: Plasma Concentration of Etoposide in the Global Population
timeFrame: Predose, before end of infusion, 1 and 4 hours after end of carboplatin infusion on Day 1 of Cycle 1 and Cycle 3 (cycle = 21 days)
Other outcomes:
Locations:
city: Fort Myers
country: United States
facility: Florida Cancer Specialists - Fort Myers (Broadway)
state: Florida
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists.
state: Florida
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers PC - Marietta
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Peoria
country: United States
facility: Illinois Cancer Care
state: Illinois
city: Zion
country: United States
facility: Cancer Treatment Centers of America - Midwestern Regional Medical Center
state: Illinois
city: Louisville
country: United States
facility: Louisville Oncology
state: Kentucky
city: Scarborough
country: United States
facility: New England Cancer Specialists
state: Maine
city: Baltimore
country: United States
facility: Weinberg CA Inst Franklin Sq
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada - Eastern Avenue
state: Nevada
city: Paramus
country: United States
facility: The Valley Hospital
state: New Jersey
city: Binghamton
country: United States
facility: Broome Oncology - Binghamton
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Chattanooga
country: United States
facility: Tennessee Oncology Chattanooga
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology PLLC - Nashville (20th Ave)
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Medical Center
state: Tennessee
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Roanoke
country: United States
facility: Blue Ridge Cancer Care
state: Virginia
city: Tacoma
country: United States
facility: Northwest Medical Specialties
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Chermside
country: Australia
facility: The Prince Charles Hospital; Oncology Dept.
state: Queensland
city: Parkville
country: Australia
facility: Royal Melbourne Hospital; Hematology and Medical Oncology
state: Victoria
city: Linz
country: Austria
facility: Kepler Universitätskliniken GmbH - Med Campus III; Abt. für Lungenkrankheiten
city: Salzburg
country: Austria
facility: Salzburger Landeskliniken; Universitätsklinik für Pneumologie/ Lungenheilkunde
city: Wien
country: Austria
facility: Klinik Penzing; Abteilung für Atemwegs- und Lungenkrankheiten
city: Wien
country: Austria
facility: Krankenhaus Nord - Klinik Floridsdorf; Abteilung Pulmologie
city: Salvador
country: Brazil
facility: Santa Casa de Misericordia de Salvador
state: BA
city: Lajeado
country: Brazil
facility: Hospital Bruno Born
state: RS
city: Porto Alegre
country: Brazil
facility: Hospital das Clinicas - UFRGS
state: RS
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo - ICESP
state: SP
city: Recoleta
country: Chile
facility: Bradford Hill Centro de Investigaciones Clinicas
city: Santiago
country: Chile
facility: OrlandiOncología
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Changchun
country: China
facility: Jilin Cancer Hospital
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Nanjing City
country: China
facility: Jiangsu Cancer Hospital
city: Shanghai City
country: China
facility: Fudan University Shanghai Cancer Center
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
city: Zhejiang
country: China
facility: Zhejiang Cancer Hospital
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc
city: Praha 4 - Krc
country: Czechia
facility: Thomayerova nemocnice
city: Praha 8
country: Czechia
facility: Fakultni nemocnice Na Bulovce
city: Bordeaux
country: France
facility: Institut Bergonie; Oncologie
city: Caen
country: France
facility: Centre Francois Baclesse; Oncologie
city: Lille
country: France
facility: Hopital Calmette; Pneumologie Oncologie Ouest
city: Marseille
country: France
facility: Hôpital Nord - AP-HM Marseille#
city: Gauting
country: Germany
facility: Asklepios-Fachklinik Muenchen-Gauting; Klinik Für Pneumologie
city: Großhansdorf
country: Germany
facility: LungenClinic Großhansdorf GmbH
city: Halle
country: Germany
facility: Krankenhaus Martha-Maria Halle-Doelau gGmbH; Klinik fuer Innere Medizin II
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg gGmbH
city: Immenhausen
country: Germany
facility: Fachklinik für Lungenerkrankungen
city: Athens
country: Greece
facility: Sotiria Chest Hospital of Athens
city: Athens
country: Greece
facility: Agioi Anargyroi; 3Rd Dept. of Medical Oncology
city: Patras
country: Greece
facility: University Hospital of Patras Medical Oncology
city: Budapest
country: Hungary
facility: Semmelweis Egyetem, AOK, Pulmonologiai Klinika
city: Budapest
country: Hungary
facility: Orszagos Koranyi TBC es Pulmonologiai Intezet
city: Debrecen
country: Hungary
facility: Debreceni Egyetem, Klinikai Kozpont, Tudogyogyaszati Klinika
city: Torokbalint
country: Hungary
facility: Tudogyogyintezet Torokbalint
city: Parma
country: Italy
facility: A.O. Universitaria Di Parma
state: Emilia-Romagna
city: Roma
country: Italy
facility: Policlinico Universitario Campus Biomedico; Uoc Oncologia Medica
state: Lazio
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
state: Lombardia
city: Milano
country: Italy
facility: Irccs Istituto Europeo di Oncologia (IEO); Divisione di Oncologia
state: Lombardia
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Ospedale Casa Sollievo Della Sofferenza; Oncologia
state: Puglia
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitaria Pisana - Ospedale Cisanello; Dipartimento Cardio Toraco Vascolare
state: Toscana
city: Fukuoka
country: Japan
facility: Kyushu University Hospital; Respiratory
city: Hyogo
country: Japan
facility: National Hospital Organization Himeji Medical Center
city: Kanagawa
country: Japan
facility: Kanagawa Cancer Center;Thoracic Oncology
city: Kyoto
country: Japan
facility: University Hospital Kyoto Prefectural University of Medicine,?Pulmonary Medicine
city: Miyagi
country: Japan
facility: Sendai Kousei Hospital; Pulmonary Medicine
city: Okayama
country: Japan
facility: Kurashiki Central Hospital; Respiratory Medicine
city: Osaka
country: Japan
facility: Kindai University Hospital; Medical Oncology
city: Osaka
country: Japan
facility: National Hospital Organization Kinki-Chuo Chest Medical Center; Internal Medicine
city: Satima
country: Japan
facility: Saitama Cancer Center; Thoracic Oncology
city: Shizuoka
country: Japan
facility: Shizuoka Cancer Center; Thoracic Oncology
city: Tokyo
country: Japan
facility: Tokyo Metropolitan Komagome Hospital; Thoracic Oncology and Respiratory Medicine
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR, Respiratory Medicine
city: Wakayama
country: Japan
facility: Wakayama Medical University Hospital; Respiratory Medicine and Medical Oncology
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Cdmx
country: Mexico
facility: Health Pharma Professional Research
state: Mexico CITY (federal District)
city: Gdansk
country: Poland
facility: Medical University of Gdansk
city: Lodz
country: Poland
facility: Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
city: Olsztyn
country: Poland
facility: Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc; Oddzial V Chemioterapii Nowotworow Pluc
city: Otwock
country: Poland
facility: Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy
city: Poznan
country: Poland
facility: Wielkopolskie Centrum Pulmonologii i Torakochirurgii w Poznaniu
city: Warszawa
country: Poland
facility: Centrum Onkologii - Inst.Im. Marii Sklodowskiej-Curie; Oncology
city: Moscovskaya Oblast
country: Russian Federation
facility: Moscow City Oncology Hospital #62
state: Moskovskaja Oblast
city: Moscow
country: Russian Federation
facility: N.N.Burdenko Main Military Clinical Hospital; Oncology Dept
state: Moskovskaja Oblast
city: Moscow
country: Russian Federation
facility: Russian Oncology Research Center n.a. N.N. Blokhin
state: Moskovskaja Oblast
city: Sankt-peterburg
country: Russian Federation
facility: City Clinical Onc.
state: Sankt Petersburg
city: St. Petersburg
country: Russian Federation
facility: Scientific Research Oncology Institute named after N.N. Petrov; Oncology
state: Sankt Petersburg
city: Novosibirsk
country: Russian Federation
facility: City Clinical Hospital No. 1
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
city: Nis
country: Serbia
facility: Clinical Center Nis; Clinic for pulmonary diseases
city: Sant Andreu de La Barca
country: Spain
facility: Hospital Univ Vall d'Hebron; Servicio de Oncologia
state: Barcelona
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario La Paz; Servicio de Oncologia
city: Malaga
country: Spain
facility: Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio; Servicio de Oncologia
city: Zaragoza
country: Spain
facility: Hosp Clinico Univ Lozano Blesa; División De Oncología Médica
city: Taipei
country: Taiwan
facility: National Taiwan Uni Hospital; Internal Medicine
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital; Chest Dept , Section of Thoracic Oncology
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation - Linkou; Chest Dept
city: Exeter
country: United Kingdom
facility: Royal Devon & Exeter Hospital; Oncology Centre
city: London
country: United Kingdom
facility: Barts and the London NHS Trust.
city: London
country: United Kingdom
facility: Guys and St Thomas NHS Foundation Trust, Guys Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital Nhs Trust; Medical Oncology
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Liu SV, Reck M, Mansfield AS, Mok T, Scherpereel A, Reinmuth N, Garassino MC, De Castro Carpeno J, Califano R, Nishio M, Orlandi F, Alatorre-Alexander J, Leal T, Cheng Y, Lee JS, Lam S, McCleland M, Deng Y, Phan S, Horn L. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 2021 Feb 20;39(6):619-630. doi: 10.1200/JCO.20.01055. Epub 2021 Jan 13.
citation: Mansfield AS, Kazarnowicz A, Karaseva N, Sanchez A, De Boer R, Andric Z, Reck M, Atagi S, Lee JS, Garassino M, Liu SV, Horn L, Wen X, Quach C, Yu W, Kabbinavar F, Lam S, Morris S, Califano R. Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial. Ann Oncol. 2020 Feb;31(2):310-317. doi: 10.1016/j.annonc.2019.10.021. Epub 2019 Dec 9.
citation: Nishio M, Sugawara S, Atagi S, Akamatsu H, Sakai H, Okamoto I, Takayama K, Hayashi H, Nakagawa Y, Kawakami T. Subgroup Analysis of Japanese Patients in a Phase III Study of Atezolizumab in Extensive-stage Small-cell Lung Cancer (IMpower133). Clin Lung Cancer. 2019 Nov;20(6):469-476.e1. doi: 10.1016/j.cllc.2019.07.005. Epub 2019 Jul 31.
citation: Horn L, Mansfield AS, Szczesna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M, Reck M, Mok T, Lam S, Shames DS, Liu J, Ding B, Lopez-Chavez A, Kabbinavar F, Lin W, Sandler A, Liu SV; IMpower133 Study Group. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med. 2018 Dec 6;379(23):2220-2229. doi: 10.1056/NEJMoa1809064. Epub 2018 Sep 25.