A Study of Carboplatin Plus Etoposide With or Without Atezolizumab in Participants With Untreated Extensive-Stage (ES) Small Cell Lung Cancer (SCLC)
- Conditions
- Small Cell Lung Carcinoma
- Interventions
- Registration Number
- NCT02763579
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 503
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Atezolizumab + Carboplatin + Etoposide Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody 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. Placebo + Carboplatin + Etoposide Placebo 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. Atezolizumab + Carboplatin + Etoposide 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. Placebo + Carboplatin + Etoposide Carboplatin 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. Atezolizumab + Carboplatin + Etoposide Carboplatin 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. Placebo + Carboplatin + Etoposide 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.
- Primary Outcome Measures
Name Time Method Duration of Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1 in the Global Population Baseline until PD or death, whichever occurs first (up to approximately 23 months) 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).
Duration of Overall Survival (OS) in the Global Population Baseline until death from any cause (up to approximately 23 months) OS is defined as the time from randomization to death from any cause.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Objective Response Rate (ORR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population Baseline until partial response (PR) or complete response (CR), whichever occurs first (up to approximately 23 months) Objective response (OR) is defined as complete response (CR) or partial response (PR) as determined by the investigator according to RECIST v1.1.
OS Rate at 1 Year and 2 Years in the Global Population 1 year, 2 years 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.
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) The percentage of participants with at least one adverse event 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) Plasma concentration of carboplatin in the Global population.
Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population First occurrence of PR or CR until PD or death, whichever occurs first (up to approximately 23 months) 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.
PFS Rate at 6 Months and at 1 Year in Global Population 6 months, 1 year 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.
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 Baseline until deterioration per symptom subscale (up to approximately 23 months) 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.
Percentage of Participants With Anti-Drug Antibodies (ADA) to Atezolizumab in the Global Population 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) The baseline prevalence and post-baseline incidence of ADAs against atezolizumab.
Maximum Observed Serum Concentration (Cmax) of Atezolizumab in the Global Population Post-dose Day 1 of Cycle 1 (cycle length = 21 days) Atezolizumab maximum observed plasma concentration (Cmax; 30 minutes following the end of the atezolizumab infusion) for each respective day.
Minimum Observed Serum Concentration (Cmin) of Atezolizumab in the Global Population Predose on Day 1 of Cycles 1, 3, 4, 8, 16 and 24 (cycle length = 21 days) Atezolizumab pre-dose plasma concentration (Cmin) for each respective day.
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) Plasma concentration of etoposide in the Global Population.
Related Research Topics
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Trial Locations
- Locations (114)
Florida Cancer Specialists - Fort Myers (Broadway)
🇺🇸Fort Myers, Florida, United States
Comprehensive Cancer Centers of Nevada - Eastern Avenue
🇺🇸Las Vegas, Nevada, United States
Tennessee Oncology Chattanooga
🇺🇸Chattanooga, Tennessee, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
New England Cancer Specialists
🇺🇸Scarborough, Maine, United States
Weinberg CA Inst Franklin Sq
🇺🇸Baltimore, Maryland, United States
Virginia Cancer Specialists, PC
🇺🇸Fairfax, Virginia, United States
Cancer Treatment Centers of America - Midwestern Regional Medical Center
🇺🇸Zion, Illinois, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Florida Cancer Specialists.
🇺🇸Saint Petersburg, Florida, United States
Salzburger Landeskliniken; Universitätsklinik für Pneumologie/ Lungenheilkunde
🇦🇹Salzburg, Austria
Northwest Georgia Oncology Centers PC - Marietta
🇺🇸Marietta, Georgia, United States
Broome Oncology - Binghamton
🇺🇸Binghamton, New York, United States
Santa Casa de Misericordia de Salvador
🇧🇷Salvador, BA, Brazil
Klinik Penzing; Abteilung für Atemwegs- und Lungenkrankheiten
🇦🇹Wien, Austria
Chris O'Brien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
Wielkopolskie Centrum Pulmonologii i Torakochirurgii w Poznaniu
🇵🇱Poznan, Poland
Hospital Ramon y Cajal; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia
🇪🇸Malaga, Spain
Hospital Universitario La Paz; Servicio de Oncologia
🇪🇸Madrid, Spain
N.N.Burdenko Main Military Clinical Hospital; Oncology Dept
🇷🇺Moscow, Moskovskaja Oblast, Russian Federation
Hôpital Nord - AP-HM Marseille#
🇫🇷Marseille, France
Chang Gung Medical Foundation - Linkou; Chest Dept
🇨🇳Taoyuan, Taiwan
Centrum Onkologii - Inst.Im. Marii Sklodowskiej-Curie; Oncology
🇵🇱Warszawa, Poland
Irccs Istituto Europeo di Oncologia (IEO); Divisione di Oncologia
🇮🇹Milano, Lombardia, Italy
Sendai Kousei Hospital; Pulmonary Medicine
🇯🇵Miyagi, Japan
City Clinical Onc.
🇷🇺Sankt-peterburg, Sankt Petersburg, Russian Federation
Russian Oncology Research Center n.a. N.N. Blokhin
🇷🇺Moscow, Moskovskaja Oblast, Russian Federation
Taipei Veterans General Hospital; Chest Dept , Section of Thoracic Oncology
🇨🇳Taipei, Taiwan
Moscow City Oncology Hospital #62
🇷🇺Moscovskaya Oblast, Moskovskaja Oblast, Russian Federation
Royal Devon & Exeter Hospital; Oncology Centre
🇬🇧Exeter, United Kingdom
Kurashiki Central Hospital; Respiratory Medicine
🇯🇵Okayama, Japan
Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy
🇵🇱Otwock, Poland
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Tennessee Oncology PLLC - Nashville (20th Ave)
🇺🇸Nashville, Tennessee, United States
Vanderbilt Medical Center
🇺🇸Nashville, Tennessee, United States
Jiangsu Cancer Hospital
🇨🇳Nanjing City, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai City, China
Zhejiang Cancer Hospital
🇨🇳Zhejiang, China
Henan Cancer Hospital
🇨🇳Zhengzhou, China
OrlandiOncología
🇨🇱Santiago, Chile
Clinical Center Nis; Clinic for pulmonary diseases
🇷🇸Nis, Serbia
National Taiwan Uni Hospital; Internal Medicine
🇨🇳Taipei, Taiwan
Scientific Research Oncology Institute named after N.N. Petrov; Oncology
🇷🇺St. Petersburg, Sankt Petersburg, Russian Federation
City Clinical Hospital No. 1
🇷🇺Novosibirsk, Russian Federation
Tudogyogyintezet Torokbalint
🇭🇺Torokbalint, Hungary
Saitama Cancer Center; Thoracic Oncology
🇯🇵Satima, Japan
Illinois Cancer Care
🇺🇸Peoria, Illinois, United States
The Valley Hospital
🇺🇸Paramus, New Jersey, United States
Beijing Cancer Hospital
🇨🇳Beijing, China
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
Bradford Hill Centro de Investigaciones Clinicas
🇨🇱Recoleta, Chile
Royal Melbourne Hospital; Hematology and Medical Oncology
🇦🇺Parkville, Victoria, Australia
Kepler Universitätskliniken GmbH - Med Campus III; Abt. für Lungenkrankheiten
🇦🇹Linz, Austria
The Prince Charles Hospital; Oncology Dept.
🇦🇺Chermside, Queensland, Australia
Krankenhaus Nord - Klinik Floridsdorf; Abteilung Pulmologie
🇦🇹Wien, Austria
Instituto do Cancer do Estado de Sao Paulo - ICESP
🇧🇷Sao Paulo, SP, Brazil
Hospital das Clinicas - UFRGS
🇧🇷Porto Alegre, RS, Brazil
Hospital Bruno Born
🇧🇷Lajeado, RS, Brazil
Jilin Cancer Hospital
🇨🇳Changchun, China
The First Affiliated Hospital of Guangzhou Medical University
🇨🇳Guangzhou, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, China
Zhongshan Hospital Fudan University
🇨🇳Shanghai, China
Thomayerova nemocnice
🇨🇿Praha 4 - Krc, Czechia
Fakultni nemocnice Na Bulovce
🇨🇿Praha 8, Czechia
LungenClinic Großhansdorf GmbH
🇩🇪Großhansdorf, Germany
Institut Bergonie; Oncologie
🇫🇷Bordeaux, France
Asklepios-Fachklinik Muenchen-Gauting; Klinik Für Pneumologie
🇩🇪Gauting, Germany
Centre Francois Baclesse; Oncologie
🇫🇷Caen, France
Krankenhaus Martha-Maria Halle-Doelau gGmbH; Klinik fuer Innere Medizin II
🇩🇪Halle, Germany
Hopital Calmette; Pneumologie Oncologie Ouest
🇫🇷Lille, France
Sotiria Chest Hospital of Athens
🇬🇷Athens, Greece
Semmelweis Egyetem, AOK, Pulmonologiai Klinika
🇭🇺Budapest, Hungary
Thoraxklinik Heidelberg gGmbH
🇩🇪Heidelberg, Germany
Fachklinik für Lungenerkrankungen
🇩🇪Immenhausen, Germany
University Hospital of Patras Medical Oncology
🇬🇷Patras, Greece
Agioi Anargyroi; 3Rd Dept. of Medical Oncology
🇬🇷Athens, Greece
Orszagos Koranyi TBC es Pulmonologiai Intezet
🇭🇺Budapest, Hungary
Debreceni Egyetem, Klinikai Kozpont, Tudogyogyaszati Klinika
🇭🇺Debrecen, Hungary
A.O. Universitaria Di Parma
🇮🇹Parma, Emilia-Romagna, Italy
Policlinico Universitario Campus Biomedico; Uoc Oncologia Medica
🇮🇹Roma, Lazio, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Lombardia, Italy
Azienda Ospedaliera Universitaria Pisana - Ospedale Cisanello; Dipartimento Cardio Toraco Vascolare
🇮🇹Pisa, Toscana, Italy
IRCCS Ospedale Casa Sollievo Della Sofferenza; Oncologia
🇮🇹San Giovanni Rotondo, Puglia, Italy
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
National Hospital Organization Kinki-Chuo Chest Medical Center; Internal Medicine
🇯🇵Osaka, Japan
Shizuoka Cancer Center; Thoracic Oncology
🇯🇵Shizuoka, Japan
Tokyo Metropolitan Komagome Hospital; Thoracic Oncology and Respiratory Medicine
🇯🇵Tokyo, Japan
The Cancer Institute Hospital of JFCR, Respiratory Medicine
🇯🇵Tokyo, Japan
Wakayama Medical University Hospital; Respiratory Medicine and Medical Oncology
🇯🇵Wakayama, Japan
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Health Pharma Professional Research
🇲🇽Cdmx, Mexico CITY (federal District), Mexico
Medical University of Gdansk
🇵🇱Gdansk, Poland
Hospital Univ Vall d'Hebron; Servicio de Oncologia
🇪🇸Sant Andreu de La Barca, Barcelona, Spain
Clinical Center of Serbia
🇷🇸Belgrade, Serbia
Hosp Clinico Univ Lozano Blesa; División De Oncología Médica
🇪🇸Zaragoza, Spain
Barts and the London NHS Trust.
🇬🇧London, United Kingdom
Northwest Medical Specialties
🇺🇸Tacoma, Washington, United States
Kindai University Hospital; Medical Oncology
🇯🇵Osaka, Japan
Blue Ridge Cancer Care
🇺🇸Roanoke, Virginia, United States
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Fakultni nemocnice Olomouc
🇨🇿Olomouc, Czechia
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Universitario Virgen del Rocio; Servicio de Oncologia
🇪🇸Sevilla, Spain
Guys and St Thomas NHS Foundation Trust, Guys Hospital
🇬🇧London, United Kingdom
Christie Hospital Nhs Trust; Medical Oncology
🇬🇧Manchester, United Kingdom
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
Florida Hospital
🇺🇸Orlando, Florida, United States
Louisville Oncology
🇺🇸Louisville, Kentucky, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States