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

Small Cell Lung Carcinoma Clinical Trial

— IMpower133  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02763579
• Other study ID #: GO30081
• Secondary ID: 2015-004861-97
• Status: Completed
• Phase: Phase 3
• Start date: June 7, 2016
• Est. completion date: July 7, 2022

Study information

• Verified date: July 2023
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 503
• Est. completion date: July 7, 2022
• Est. primary completion date: April 24, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Small Cell Lung Carcinoma

Intervention

Drug:
• 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).
• 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).
• 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).
• 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).

Locations

Country	Name	City	State
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	The Prince Charles Hospital; Oncology Dept.	Chermside	Queensland
Australia	Royal Melbourne Hospital; Hematology and Medical Oncology	Parkville	Victoria
Austria	Kepler Universitätskliniken GmbH - Med Campus III; Abt. für Lungenkrankheiten	Linz
Austria	Salzburger Landeskliniken; Universitätsklinik für Pneumologie/ Lungenheilkunde	Salzburg
Austria	Klinik Penzing; Abteilung für Atemwegs- und Lungenkrankheiten	Wien
Austria	Krankenhaus Nord - Klinik Floridsdorf; Abteilung Pulmologie	Wien
Brazil	Hospital Bruno Born	Lajeado	RS
Brazil	Hospital das Clinicas - UFRGS	Porto Alegre	RS
Brazil	Santa Casa de Misericordia de Salvador	Salvador	BA
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP
Chile	Bradford Hill Centro de Investigaciones Clinicas	Recoleta
Chile	OrlandiOncología	Santiago
China	Beijing Cancer Hospital	Beijing
China	Jilin Cancer Hospital	Changchun
China	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou
China	Harbin Medical University Cancer Hospital	Harbin
China	Jiangsu Cancer Hospital	Nanjing City
China	Zhongshan Hospital Fudan University	Shanghai
China	Fudan University Shanghai Cancer Center	Shanghai City
China	Zhejiang Cancer Hospital	Zhejiang
China	Henan Cancer Hospital	Zhengzhou
Czechia	Fakultni nemocnice Olomouc	Olomouc
Czechia	Thomayerova nemocnice	Praha 4 - Krc
Czechia	Fakultni nemocnice Na Bulovce	Praha 8
France	Institut Bergonie; Oncologie	Bordeaux
France	Centre Francois Baclesse; Oncologie	Caen
France	Hopital Calmette; Pneumologie Oncologie Ouest	Lille
France	Hôpital Nord - AP-HM Marseille#	Marseille
Germany	Asklepios-Fachklinik Muenchen-Gauting; Klinik Für Pneumologie	Gauting
Germany	LungenClinic Großhansdorf GmbH	Großhansdorf
Germany	Krankenhaus Martha-Maria Halle-Doelau gGmbH; Klinik fuer Innere Medizin II	Halle
Germany	Thoraxklinik Heidelberg gGmbH	Heidelberg
Germany	Fachklinik für Lungenerkrankungen	Immenhausen
Greece	Agioi Anargyroi; 3Rd Dept. of Medical Oncology	Athens
Greece	Sotiria Chest Hospital of Athens	Athens
Greece	University Hospital of Patras Medical Oncology	Patras
Hungary	Orszagos Koranyi TBC es Pulmonologiai Intezet	Budapest
Hungary	Semmelweis Egyetem, AOK, Pulmonologiai Klinika	Budapest
Hungary	Debreceni Egyetem, Klinikai Kozpont, Tudogyogyaszati Klinika	Debrecen
Hungary	Tudogyogyintezet Torokbalint	Torokbalint
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano	Lombardia
Italy	Irccs Istituto Europeo di Oncologia (IEO); Divisione di Oncologia	Milano	Lombardia
Italy	A.O. Universitaria Di Parma	Parma	Emilia-Romagna
Italy	Azienda Ospedaliera Universitaria Pisana - Ospedale Cisanello; Dipartimento Cardio Toraco Vascolare	Pisa	Toscana
Italy	Policlinico Universitario Campus Biomedico; Uoc Oncologia Medica	Roma	Lazio
Italy	IRCCS Ospedale Casa Sollievo Della Sofferenza; Oncologia	San Giovanni Rotondo	Puglia
Japan	Kyushu University Hospital; Respiratory	Fukuoka
Japan	National Hospital Organization Himeji Medical Center	Hyogo
Japan	Kanagawa Cancer Center;Thoracic Oncology	Kanagawa
Japan	University Hospital Kyoto Prefectural University of Medicine,?Pulmonary Medicine	Kyoto
Japan	Sendai Kousei Hospital; Pulmonary Medicine	Miyagi
Japan	Kurashiki Central Hospital; Respiratory Medicine	Okayama
Japan	Kindai University Hospital; Medical Oncology	Osaka
Japan	National Hospital Organization Kinki-Chuo Chest Medical Center; Internal Medicine	Osaka
Japan	Saitama Cancer Center; Thoracic Oncology	Satima
Japan	Shizuoka Cancer Center; Thoracic Oncology	Shizuoka
Japan	The Cancer Institute Hospital of JFCR, Respiratory Medicine	Tokyo
Japan	Tokyo Metropolitan Komagome Hospital; Thoracic Oncology and Respiratory Medicine	Tokyo
Japan	Wakayama Medical University Hospital; Respiratory Medicine and Medical Oncology	Wakayama
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Mexico	Health Pharma Professional Research	Cdmx	Mexico CITY (federal District)
Poland	Medical University of Gdansk	Gdansk
Poland	Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi	Lodz
Poland	Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc; Oddzial V Chemioterapii Nowotworow Pluc	Olsztyn
Poland	Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy	Otwock
Poland	Wielkopolskie Centrum Pulmonologii i Torakochirurgii w Poznaniu	Poznan
Poland	Centrum Onkologii - Inst.Im. Marii Sklodowskiej-Curie; Oncology	Warszawa
Russian Federation	Moscow City Oncology Hospital #62	Moscovskaya Oblast	Moskovskaja Oblast
Russian Federation	N.N.Burdenko Main Military Clinical Hospital; Oncology Dept	Moscow	Moskovskaja Oblast
Russian Federation	Russian Oncology Research Center n.a. N.N. Blokhin	Moscow	Moskovskaja Oblast
Russian Federation	City Clinical Hospital No. 1	Novosibirsk
Russian Federation	City Clinical Onc.	Sankt-peterburg	Sankt Petersburg
Russian Federation	Scientific Research Oncology Institute named after N.N. Petrov; Oncology	St. Petersburg	Sankt Petersburg
Serbia	Clinical Center of Serbia	Belgrade
Serbia	Clinical Center Nis; Clinic for pulmonary diseases	Nis
Spain	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid
Spain	Hospital Universitario La Paz; Servicio de Oncologia	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia	Malaga
Spain	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Sant Andreu de La Barca	Barcelona
Spain	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla
Spain	Hosp Clinico Univ Lozano Blesa; División De Oncología Médica	Zaragoza
Taiwan	National Taiwan Uni Hospital; Internal Medicine	Taipei
Taiwan	Taipei Veterans General Hospital; Chest Dept , Section of Thoracic Oncology	Taipei
Taiwan	Chang Gung Medical Foundation - Linkou; Chest Dept	Taoyuan
United Kingdom	Royal Devon & Exeter Hospital; Oncology Centre	Exeter
United Kingdom	Barts and the London NHS Trust.	London
United Kingdom	Guys and St Thomas NHS Foundation Trust, Guys Hospital	London
United Kingdom	Christie Hospital Nhs Trust; Medical Oncology	Manchester
United States	Weinberg CA Inst Franklin Sq	Baltimore	Maryland
United States	Broome Oncology - Binghamton	Binghamton	New York
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	Tennessee Oncology Chattanooga	Chattanooga	Tennessee
United States	Rush University Medical Center	Chicago	Illinois
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Florida Cancer Specialists - Fort Myers (Broadway)	Fort Myers	Florida
United States	Comprehensive Cancer Centers of Nevada - Eastern Avenue	Las Vegas	Nevada
United States	Louisville Oncology	Louisville	Kentucky
United States	University of Wisconsin	Madison	Wisconsin
United States	Northwest Georgia Oncology Centers PC - Marietta	Marietta	Georgia
United States	Tennessee Oncology PLLC - Nashville (20th Ave)	Nashville	Tennessee
United States	Vanderbilt Medical Center	Nashville	Tennessee
United States	Florida Hospital	Orlando	Florida
United States	The Valley Hospital	Paramus	New Jersey
United States	Illinois Cancer Care	Peoria	Illinois
United States	Blue Ridge Cancer Care	Roanoke	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	Florida Cancer Specialists.	Saint Petersburg	Florida
United States	New England Cancer Specialists	Scarborough	Maine
United States	Northwest Medical Specialties	Tacoma	Washington
United States	Cancer Treatment Centers of America - Midwestern Regional Medical Center	Zion	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Brazil,  Chile,  China,  Czechia,  France,  Germany,  Greece,  Hungary,  Italy,  Japan,  Korea, Republic of,  Mexico,  Poland,  Russian Federation,  Serbia,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1 in the Global Population	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least 20% increase in the sum of the longest diameter of target lesions compared to baseline, or unequivocal progression in non-target lesion(s), or the appearance of new lesion(s).	Baseline until PD or death, whichever occurs first (up to approximately 23 months)
Primary	Duration of Overall Survival (OS) in the Global Population	OS is defined as the time from randomization to death from any cause.	Baseline until death from any cause (up to approximately 23 months)
Secondary	Percentage of Participants With Objective Response Rate (ORR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population	Objective response (OR) is defined as complete response (CR) or partial response (PR) as determined by the investigator according to RECIST v1.1.	Baseline until partial response (PR) or complete response (CR), whichever occurs first (up to approximately 23 months)
Secondary	Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population	DOR is defined as the time interval from first occurrence of a documented objective response to the time of disease progression as determined by the investigator using RECIST v1.1 or death from any cause, whichever comes first.	First occurrence of PR or CR until PD or death, whichever occurs first (up to approximately 23 months)
Secondary	PFS Rate at 6 Months and at 1 Year in Global Population	PFS rates at 6 months and at 1 year is defined as the proportion of participants who are alive without disease progression 6 months and 1 year after randomization, respectively.	6 months, 1 year
Secondary	OS Rate at 1 Year and 2 Years in the Global Population	OS rates at 1 and 2 years is defined as the proportion of participants who are alive 1 year and 2 years after randomization, respectively.	1 year, 2 years
Secondary	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	TTD according to the EORTC QLQ-C30 and EORTC QLQ-LC13 measures were evaluated in each of the following linearly transformed symptom scores: cough, dyspnea (single item), dyspnea (multi-item subscale), chest pain, or arm/shoulder pain. The linear transformation gives each individual symptom subscale a possible score of 0 to 100. For the symptom to be considered "deteriorated," a score increase of =10 points above baseline must be held for at least two consecutive assessments or an initial score increase of =10 points is followed by death within 3 weeks from the last assessment. A = 10-point change in the symptoms subscale score is perceived by participants as clinically significant.	Baseline until deterioration per symptom subscale (up to approximately 23 months)
Secondary	Percentage of Participants With at Least One Adverse Event in the Global Population	The percentage of participants with at least one adverse event in the global population.	Baseline until up to 90 days after end of treatment (up to approximately 49 months)
Secondary	Percentage of Participants With Anti-Drug Antibodies (ADA) to Atezolizumab in the Global Population	The baseline prevalence and post-baseline incidence of ADAs against atezolizumab.	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)
Secondary	Maximum Observed Serum Concentration (Cmax) of Atezolizumab in the Global Population	Atezolizumab maximum observed plasma concentration (Cmax; 30 minutes following the end of the atezolizumab infusion) for each respective day.	Post-dose Day 1 of Cycle 1 (cycle length = 21 days)
Secondary	Minimum Observed Serum Concentration (Cmin) of Atezolizumab in the Global Population	Atezolizumab pre-dose plasma concentration (Cmin) for each respective day.	Predose on Day 1 of Cycles 1, 3, 4, 8, 16 and 24 (cycle length = 21 days)
Secondary	Plasma Concentration of Carboplatin in the Global Population	Plasma concentration of carboplatin in the Global population.	Predose, before end of infusion, and after end of carboplatin infusion on Day 1 of Cycle 1 and Cycle 3 (cycle = 21 days)
Secondary	Plasma Concentration of Etoposide in the Global Population	Plasma concentration of etoposide in the Global Population.	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)