A Study of Carboplatin Plus Etoposide With or Without Atezolizumab in Participants With Untreated Extensive-Stage (ES) Small Cell Lung Cancer (SCLC)

NCT ID: NCT02763579

Last Updated: 2023-07-28

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

503 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-06-07

Study Completion Date

2022-07-07

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Small Cell Lung Carcinoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Atezolizumab + Carboplatin + Etoposide

Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m\^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.

Group Type EXPERIMENTAL

Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody

Intervention Type DRUG

Atezolizumab intravenous infusion was administered at a dose of 1200 mg on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4) and maintenance phase (Cycle 5 onward).

Carboplatin

Intervention Type DRUG

Carboplatin intravenous infusion to achieve an initial target AUC of 5 mg/mL/min was administered on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4).

Etoposide

Intervention Type DRUG

Etoposide intravenous infusion was administered at a dose of 100 mg/m\^2 on Days 1, 2, and 3 of each 21-day cycle during the induction phase (Cycles 1-4).

Placebo + Carboplatin + Etoposide

Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m\^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.

Group Type ACTIVE_COMPARATOR

Carboplatin

Intervention Type DRUG

Carboplatin intravenous infusion to achieve an initial target AUC of 5 mg/mL/min was administered on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4).

Etoposide

Intervention Type DRUG

Etoposide intravenous infusion was administered at a dose of 100 mg/m\^2 on Days 1, 2, and 3 of each 21-day cycle during the induction phase (Cycles 1-4).

Placebo

Intervention Type DRUG

Placebo intravenous infusion was administered on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4) and maintenance phase (Cycle 5 onward).

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody

Atezolizumab intravenous infusion was administered at a dose of 1200 mg on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4) and maintenance phase (Cycle 5 onward).

Intervention Type DRUG

Carboplatin

Carboplatin intravenous infusion to achieve an initial target AUC of 5 mg/mL/min was administered on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4).

Intervention Type DRUG

Etoposide

Etoposide intravenous infusion was administered at a dose of 100 mg/m\^2 on Days 1, 2, and 3 of each 21-day cycle during the induction phase (Cycles 1-4).

Intervention Type DRUG

Placebo

Placebo intravenous infusion was administered on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4) and maintenance phase (Cycle 5 onward).

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

MPDL3280A, RO5541267, Tecentriq

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Florida Cancer Specialists - Fort Myers (Broadway)

Fort Myers, Florida, United States

Site Status

Florida Hospital

Orlando, Florida, United States

Site Status

Florida Cancer Specialists.

St. Petersburg, Florida, United States

Site Status

Northwest Georgia Oncology Centers PC - Marietta

Marietta, Georgia, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Illinois Cancer Care

Peoria, Illinois, United States

Site Status

Cancer Treatment Centers of America - Midwestern Regional Medical Center

Zion, Illinois, United States

Site Status

Louisville Oncology

Louisville, Kentucky, United States

Site Status

New England Cancer Specialists

Scarborough, Maine, United States

Site Status

Weinberg CA Inst Franklin Sq

Baltimore, Maryland, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Comprehensive Cancer Centers of Nevada - Eastern Avenue

Las Vegas, Nevada, United States

Site Status

The Valley Hospital

Paramus, New Jersey, United States

Site Status

Broome Oncology - Binghamton

Binghamton, New York, United States

Site Status

Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status

Tennessee Oncology Chattanooga

Chattanooga, Tennessee, United States

Site Status

Tennessee Oncology PLLC - Nashville (20th Ave)

Nashville, Tennessee, United States

Site Status

Vanderbilt Medical Center

Nashville, Tennessee, United States

Site Status

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Site Status

Blue Ridge Cancer Care

Roanoke, Virginia, United States

Site Status

Northwest Medical Specialties

Tacoma, Washington, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia

Site Status

The Prince Charles Hospital; Oncology Dept.

Chermside, Queensland, Australia

Site Status

Royal Melbourne Hospital; Hematology and Medical Oncology

Parkville, Victoria, Australia

Site Status

Kepler Universitätskliniken GmbH - Med Campus III; Abt. für Lungenkrankheiten

Linz, , Austria

Site Status

Salzburger Landeskliniken; Universitätsklinik für Pneumologie/ Lungenheilkunde

Salzburg, , Austria

Site Status

Klinik Penzing; Abteilung für Atemwegs- und Lungenkrankheiten

Vienna, , Austria

Site Status

Krankenhaus Nord - Klinik Floridsdorf; Abteilung Pulmologie

Vienna, , Austria

Site Status

Santa Casa de Misericordia de Salvador

Salvador, Estado de Bahia, Brazil

Site Status

Hospital Bruno Born

Lajeado, Rio Grande do Sul, Brazil

Site Status

Hospital das Clinicas - UFRGS

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo, Brazil

Site Status

Bradford Hill Centro de Investigaciones Clinicas

Recoleta, , Chile

Site Status

OrlandiOncología

Santiago, , Chile

Site Status

Beijing Cancer Hospital

Beijing, , China

Site Status

Jilin Cancer Hospital

Changchun, , China

Site Status

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, , China

Site Status

Harbin Medical University Cancer Hospital

Harbin, , China

Site Status

Jiangsu Cancer Hospital

Nanjing, , China

Site Status

Zhongshan Hospital Fudan University

Shanghai, , China

Site Status

Fudan University Shanghai Cancer Center

Shanghai, , China

Site Status

Zhejiang Cancer Hospital

Zhejiang, , China

Site Status

Henan Cancer Hospital

Zhengzhou, , China

Site Status

Fakultni nemocnice Olomouc

Olomouc, , Czechia

Site Status

Fakultni nemocnice Na Bulovce

Prague, , Czechia

Site Status

Thomayerova nemocnice

Praha 4 - Krc, , Czechia

Site Status

Institut Bergonie; Oncologie

Bordeaux, , France

Site Status

Centre Francois Baclesse; Oncologie

Caen, , France

Site Status

Hopital Calmette; Pneumologie Oncologie Ouest

Lille, , France

Site Status

Hôpital Nord - AP-HM Marseille#

Marseille, , France

Site Status

Asklepios-Fachklinik Muenchen-Gauting; Klinik Für Pneumologie

Gauting, , Germany

Site Status

LungenClinic Großhansdorf GmbH

Großhansdorf, , Germany

Site Status

Krankenhaus Martha-Maria Halle-Doelau gGmbH; Klinik fuer Innere Medizin II

Halle, , Germany

Site Status

Thoraxklinik Heidelberg gGmbH

Heidelberg, , Germany

Site Status

Fachklinik für Lungenerkrankungen

Immenhausen, , Germany

Site Status

Sotiria Chest Hospital of Athens

Athens, , Greece

Site Status

Agioi Anargyroi; 3Rd Dept. of Medical Oncology

Athens, , Greece

Site Status

University Hospital of Patras Medical Oncology

Pátrai, , Greece

Site Status

Semmelweis Egyetem, AOK, Pulmonologiai Klinika

Budapest, , Hungary

Site Status

Orszagos Koranyi TBC es Pulmonologiai Intezet

Budapest, , Hungary

Site Status

Debreceni Egyetem, Klinikai Kozpont, Tudogyogyaszati Klinika

Debrecen, , Hungary

Site Status

Tudogyogyintezet Torokbalint

Törökbálint, , Hungary

Site Status

IRCCS Ospedale Casa Sollievo Della Sofferenza; Oncologia

San Giovanni Rotondo, Apulia, Italy

Site Status

A.O. Universitaria Di Parma

Parma, Emilia-Romagna, Italy

Site Status

Policlinico Universitario Campus Biomedico; Uoc Oncologia Medica

Rome, Lazio, Italy

Site Status

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Lombardy, Italy

Site Status

Irccs Istituto Europeo di Oncologia (IEO); Divisione di Oncologia

Milan, Lombardy, Italy

Site Status

Azienda Ospedaliera Universitaria Pisana - Ospedale Cisanello; Dipartimento Cardio Toraco Vascolare

Pisa, Tuscany, Italy

Site Status

Kyushu University Hospital; Respiratory

Fukuoka, , Japan

Site Status

National Hospital Organization Himeji Medical Center

Hyōgo, , Japan

Site Status

Kanagawa Cancer Center;Thoracic Oncology

Kanagawa, , Japan

Site Status

University Hospital Kyoto Prefectural University of Medicine,?Pulmonary Medicine

Kyoto, , Japan

Site Status

Sendai Kousei Hospital; Pulmonary Medicine

Miyagi, , Japan

Site Status

Kurashiki Central Hospital; Respiratory Medicine

Okayama, , Japan

Site Status

Kindai University Hospital; Medical Oncology

Osaka, , Japan

Site Status

National Hospital Organization Kinki-Chuo Chest Medical Center; Internal Medicine

Osaka, , Japan

Site Status

Saitama Cancer Center; Thoracic Oncology

Satima, , Japan

Site Status

Shizuoka Cancer Center; Thoracic Oncology

Shizuoka, , Japan

Site Status

Tokyo Metropolitan Komagome Hospital; Thoracic Oncology and Respiratory Medicine

Tokyo, , Japan

Site Status

The Cancer Institute Hospital of JFCR, Respiratory Medicine

Tokyo, , Japan

Site Status

Wakayama Medical University Hospital; Respiratory Medicine and Medical Oncology

Wakayama, , Japan

Site Status

Health Pharma Professional Research

Mexico City, Mexico CITY (federal District), Mexico

Site Status

Medical University of Gdansk

Gdansk, , Poland

Site Status

Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi

Lodz, , Poland

Site Status

Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc; Oddzial V Chemioterapii Nowotworow Pluc

Olsztyn, , Poland

Site Status

Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy

Otwock, , Poland

Site Status

Wielkopolskie Centrum Pulmonologii i Torakochirurgii w Poznaniu

Poznan, , Poland

Site Status

Centrum Onkologii - Inst.Im. Marii Sklodowskiej-Curie; Oncology

Warsaw, , Poland

Site Status

Moscow City Oncology Hospital #62

Moscovskaya Oblast, Moscow Oblast, Russia

Site Status

N.N.Burdenko Main Military Clinical Hospital; Oncology Dept

Moscow, Moscow Oblast, Russia

Site Status

Russian Oncology Research Center n.a. N.N. Blokhin

Moscow, Moscow Oblast, Russia

Site Status

Scientific Research Oncology Institute named after N.N. Petrov; Oncology

Saint Petersburg, Sankt-Peterburg, Russia

Site Status

City Clinical Onc.

Saint Petersburg, Sankt-Peterburg, Russia

Site Status

City Clinical Hospital No. 1

Novosibirsk, , Russia

Site Status

Clinical Center of Serbia

Belgrade, , Serbia

Site Status

Clinical Center Nis; Clinic for pulmonary diseases

Niš, , Serbia

Site Status

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Sant Andreu de la Barca, Barcelona, Spain

Site Status

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, , Spain

Site Status

Hospital Universitario La Paz; Servicio de Oncologia

Madrid, , Spain

Site Status

Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia

Málaga, , Spain

Site Status

Hospital Universitario Virgen del Rocio; Servicio de Oncologia

Seville, , Spain

Site Status

Hosp Clinico Univ Lozano Blesa; División De Oncología Médica

Zaragoza, , Spain

Site Status

National Taiwan Uni Hospital; Internal Medicine

Taipei, , Taiwan

Site Status

Taipei Veterans General Hospital; Chest Dept , Section of Thoracic Oncology

Taipei, , Taiwan

Site Status

Chang Gung Medical Foundation - Linkou; Chest Dept

Taoyuan District, , Taiwan

Site Status

Royal Devon & Exeter Hospital; Oncology Centre

Exeter, , United Kingdom

Site Status

Barts and the London NHS Trust.

London, , United Kingdom

Site Status

Guys and St Thomas NHS Foundation Trust, Guys Hospital

London, , United Kingdom

Site Status

Christie Hospital Nhs Trust; Medical Oncology

Manchester, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Australia Austria Brazil Chile China Czechia France Germany Greece Hungary Italy Japan Mexico Poland Russia Serbia South Korea Spain Taiwan United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

Bernabe R, Liu SV, Sanchez-Gastaldo A, Alonso Garcia M. Long-Term Survival and Stable Disease in a Patient with Extensive-Stage Small-Cell Lung Cancer after Treatment with Carboplatin, Etoposide and Atezolizumab. Oncol Ther. 2024 Mar;12(1):175-182. doi: 10.1007/s40487-023-00257-0. Epub 2024 Jan 27.

Reference Type DERIVED
PMID: 38280181 (View on PubMed)

Liu SV, Mok TSK, Nabet BY, Mansfield AS, De Boer R, Losonczy G, Sugawara S, Dziadziuszko R, Krzakowski M, Smolin A, Hochmair MJ, Garassino MC, Gay CM, Heymach JV, Byers LA, Lam S, Cardona A, Morris S, Adler L, Shames DS, Reck M. Clinical and molecular characterization of long-term survivors with extensive-stage small cell lung cancer treated with first-line atezolizumab plus carboplatin and etoposide. Lung Cancer. 2023 Dec;186:107418. doi: 10.1016/j.lungcan.2023.107418. Epub 2023 Oct 31.

Reference Type DERIVED
PMID: 37931445 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33439693 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31959349 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31466854 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30280641 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2015-004861-97

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GO30081

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.