A Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Patients With Untreated Extensive-Stage Small Cell Lung Cancer
- Conditions
- Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT04256421
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This study will evaluate the efficacy of tiragolumab plus atezolizumab and carboplatin and etoposide (CE) compared with placebo plus atezolizumab and CE in participants with chemotherapy-naive extensive-stage small cell lung cancer (ES-SCLC). Eligible participants will be stratified by Eastern Cooperative Oncology Group (ECOG) Performance Status (0 vs. 1), LDH (\</= upper limit of normal \[ULN\] vs. \> ULN), and presence or history of brain metastasis (yes vs. no) and randomly assigned in a 1:1 ratio to receive one of the following treatment regimens during induction phase:
* Arm A: Tiragolumab plus atezolizumab plus CE
* Arm B: Placebo plus atezolizumab plus CE
Following the induction phase, participants will continue maintenance therapy with either atezolizumab plus tiragolumab (Arm A) or atezolizumab plus placebo (Arm B).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 490
- Histologically or cytologically confirmed extensive-stage small cell lung cancer (ES-SCLC)
- No prior systemic treatment for ES-SCLC
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (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
- Symptomatic or actively progressing central nervous system (CNS) metastases
- Malignancies other than small cell lung cancer (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
- Active or history of autoimmune disease or immune deficiency
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
- Positive test result for human immunodeficiency virus (HIV)
- Active hepatitis B or hepatitis C
- Severe infection at the time of randomization
- Treatment with any other investigational agent within 28 days prior to initiation of study treatment
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA-4), anti-TIGIT, anti-PD-1, and anti-PD-L1 therapeutic antibodies
- Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug elimination half-lives prior to randomization
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + Atezolizumab + CE Placebo Participants will receive atezolizumab on Day 1 of each 21-day cycle followed by placebo on Day 1 of each 21-day cycle. Carboplatin will be administered followed by etoposide on Day 1 for 4 cycles. Participants will also receive etoposide on Days 2 and 3. Tiragolumab + Atezolizumab + CE Atezolizumab Participants will receive atezolizumab on Day 1 of each 21-day cycle followed by tiragolumab on Day 1 of each 21-day cycle. Carboplatin will be administered followed by etoposide on Day 1 for 4 cycles. Participants will also receive etoposide on Days 2 and 3. Placebo + Atezolizumab + CE Atezolizumab Participants will receive atezolizumab on Day 1 of each 21-day cycle followed by placebo on Day 1 of each 21-day cycle. Carboplatin will be administered followed by etoposide on Day 1 for 4 cycles. Participants will also receive etoposide on Days 2 and 3. Placebo + Atezolizumab + CE Etoposide Participants will receive atezolizumab on Day 1 of each 21-day cycle followed by placebo on Day 1 of each 21-day cycle. Carboplatin will be administered followed by etoposide on Day 1 for 4 cycles. Participants will also receive etoposide on Days 2 and 3. Placebo + Atezolizumab + CE Carboplatin Participants will receive atezolizumab on Day 1 of each 21-day cycle followed by placebo on Day 1 of each 21-day cycle. Carboplatin will be administered followed by etoposide on Day 1 for 4 cycles. Participants will also receive etoposide on Days 2 and 3. Tiragolumab + Atezolizumab + CE Tiragolumab Participants will receive atezolizumab on Day 1 of each 21-day cycle followed by tiragolumab on Day 1 of each 21-day cycle. Carboplatin will be administered followed by etoposide on Day 1 for 4 cycles. Participants will also receive etoposide on Days 2 and 3. Tiragolumab + Atezolizumab + CE Carboplatin Participants will receive atezolizumab on Day 1 of each 21-day cycle followed by tiragolumab on Day 1 of each 21-day cycle. Carboplatin will be administered followed by etoposide on Day 1 for 4 cycles. Participants will also receive etoposide on Days 2 and 3. Tiragolumab + Atezolizumab + CE Etoposide Participants will receive atezolizumab on Day 1 of each 21-day cycle followed by tiragolumab on Day 1 of each 21-day cycle. Carboplatin will be administered followed by etoposide on Day 1 for 4 cycles. Participants will also receive etoposide on Days 2 and 3.
- Primary Outcome Measures
Name Time Method Investigator-Assessed Progression Free Survival (PFS) in the Primary Analysis Set (PAS) From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 50 months) Overall Survival (OS) in the PAS From randomization to death from any cause (up to 50 months)
- Secondary Outcome Measures
Name Time Method PFS in the Full Analysis Set (FAS) From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 50 months) OS in the FAS From randomization to death from any cause (up to 50 months) Investigator-Assessed Confirmed Objective Response Rate (ORR) in the PAS From randomization up to 50 months Investigator-Assessed Confirmed ORR in the FAS From randomization up to 50 months Investigator-Assessed Duration of Response (DOR) in the PAS From the first occurrence of a documented confirmed objective response to disease progression or death from any cause, whichever occurs first (up to 50 months) Investigator-Assessed DOR in the FAS From the first occurrence of a documented confirmed objective response to disease progression or death from any cause, whichever occurs first (up to 50 months) Investigator-Assessed PFS Rates at 6 Months and 12 Months in the PAS 6 months, 12 months Investigator-Assessed PFS Rates at 6 Months and 12 Months in the FAS 6 months, 12 months Overall Survival Rates at 12 Months and 24 Months in the PAS 12 months, 24 months Overall Survival Rates at 12 Months and 24 Months in the FAS 12 months, 24 months Time to Confirmed Deterioration (TTCD) Assessed Using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core (QLQ-C30) Score in the PAS From randomization until the first confirmed clinically meaningful deterioration up to 50 months TTCD using EORTC QLQ-C30 is an initial 10-point decrease in global health status (GHS)/quality of life (QoL) and functioning from baseline that must be held for at least two consecutive assessments or an initial clinically meaningful decrease above baseline followed by death. EORTC QLQ-C30: a self-reported measure, consisting of 30 questions that assess 5 aspects of participants functioning (physical, emotional, role, cognitive and social), 3 symptom scales (fatigue, nausea and vomiting and pain), GHS and QoL, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) with a recall period of the previous week. Functioning items are scored on a 4-point scale: 1=Not at all to 4=Very much, with higher score indicating worse outcome. Symptom items (GHS and QoL) are scored on a 7-point scale: 1=Very poor to 7=Excellent. Scores will be linearly transformed with a minimum score of 0 and maximum score of 100. Higher score indicates better outcome.
TTCD Assessed Using EORTC QLQ-C30 Score in the FAS From randomization until the first confirmed clinically meaningful deterioration up to 50 months TTCD using EORTC QLQ-C30 is an initial 10-point decrease in global health status (GHS)/quality of life (QoL) and functioning from baseline that must be held for at least two consecutive assessments or an initial clinically meaningful decrease above baseline followed by death. EORTC QLQ-C30: a self-reported measure, consisting of 30 questions that assess 5 aspects of participants functioning (physical, emotional, role, cognitive and social), 3 symptom scales (fatigue, nausea and vomiting and pain), GHS and QoL, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) with a recall period of the previous week. Functioning items are scored on a 4-point scale: 1=Not at all to 4=Very much, with higher score indicating worse outcome. Symptom items (GHS and QoL) are scored on a 7-point scale: 1=Very poor to 7=Excellent. Scores will be linearly transformed with a minimum score of 0 and maximum score of 100. Higher score indicates better outcome.
Percentage of Participants With Adverse Events Up to 50 months Minimum Serum Concentration (Cmin) of Tiragolumab Predose and postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at treatment discontinuation (TD) visit (up to 50 months) Cmin of Atezolizumab Predose and postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at TD visit (up to 50 months) Maximum Serum Concentration (Cmax) of Tiragolumab Predose and postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at TD visit (up to 50 months) Cmax of Atezolizumab Predose and postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at TD visit (up to 50 months) Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab Predose on Day 1 of Cycles 1 (each cycle is 21 days), 2, 3, 4, 8,12 and 16 and at TD visit (up to 50 months) Percentage of Participants With ADAs to Atezolizumab Predose on Day 1 of Cycles 1 (each cycle is 21 days), 2, 3, 4, 8,12 and 16 and at TD visit (up to 50 months) Change from Baseline in EuroQol 5-Dimension, 5-Level (EQ-5D-5L) Index-based and Visual Analog Scale Scores From baseline up to 50 months The EQ-5D-5L is a validated self-report health status questionnaire that is used to calculate a health status utility score for use in health economic analyses. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, as well as a visual analog scale (VAS) that measures health state. A single composite score is calculated based on the responses as an indicator of the participant's health status.
Trial Locations
- Locations (118)
LungenClinic Großhansdorf GmbH
🇩🇪Großhansdorf, Germany
Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad
🇵🇱Warszawa, Poland
Istanbul University Cerrahpa?a-Cerrahpa?a Medical Faculty
🇹🇷Istanbul, Turkey
Rocky Mountain Cancer Centers - Lone Tree
🇺🇸Lone Tree, Colorado, United States
MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)
🇺🇸Washington, District of Columbia, United States
Florida Cancer Specialists
🇺🇸Fort Myers, Florida, United States
SCRI Florida Cancer Specialists North
🇺🇸Sarasota, Florida, United States
Northwest Georgia Oncology Centers PC - Marietta
🇺🇸Marietta, Georgia, United States
Illinois Cancer Care
🇺🇸Peoria, Illinois, United States
New England Cancer Specialists
🇺🇸Scarborough, Maine, United States
Weinberg Cancer Institution at Franklin Square
🇺🇸Baltimore, Maryland, United States
Minnesota Oncology Hematology
🇺🇸Minneapolis, Minnesota, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Henderson, Nevada, United States
Sarah Cannon Research Institute / Tennessee Oncology
🇺🇸Chattanooga, Tennessee, United States
Sarah Cannon Research Inst.
🇺🇸Nashville, Tennessee, United States
Texas Oncology Cancer Center
🇺🇸Austin, Texas, United States
Chris O'Brien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
Nepean Hospital
🇦🇺Kingswood, New South Wales, Australia
Tiroler Landeskrankenanstalten Ges.M.B.H.
🇦🇹Innsbruck, Austria
Klinik Penzing
🇦🇹Wien, Austria
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Krankenhaus Nord - Klinik Floridsdorf
🇦🇹Wien, Austria
AZ St Maarten Campus Leopoldstr
🇧🇪Mechelen, Belgium
Blue Ridge Cancer Care
🇺🇸Roanoke, Virginia, United States
Sunshine Coast University Hospital
🇦🇺Birtinya, Queensland, Australia
Lyell McEwin Hospital
🇦🇺Elizabeth Vale, South Australia, Australia
University of Wisconsin School of Medicine and Public Health
🇺🇸Madison, Wisconsin, United States
Clinique Ste-Elisabeth
🇧🇪Namur, Belgium
AZ Delta (Campus Rumbeke)
🇧🇪Roeselare, Belgium
Vitaz
🇧🇪Sint Niklaas, Belgium
Hospital Sao Rafael - HSR
🇧🇷Salvador, Bahia, Brazil
Oncocentro Serviços Médicos e Hospitalares Ltda
🇧🇷Fortaleza, Ceará, Brazil
Hospital de Clínicas de Passo Fundo
🇧🇷Passo Fundo, Rio Grande Do Sul, Brazil
Hospital Nossa Senhora da Conceicao
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Instituto do Cancer do Estado de Sao Paulo - ICESP
🇧🇷Sao Paulo, São Paulo, Brazil
Fakultni nemocnice Olomouc
🇨🇿Olomouc, Czechia
Vitkovicka Nemocnice Bma, A.S.
🇨🇿Ostrava, Czechia
Thomayerova nemocnice
🇨🇿Praha 4 - Krc, Czechia
Helios Klinikum Emil von Behring GmbH
🇩🇪Berlin, Germany
Asklepios Klinik Harburg
🇩🇪Hamburg, Germany
Fachklinik für Lungenerkrankungen
🇩🇪Immenhausen, Germany
Universitätsklinikum Schleswig-Holstein
🇩🇪Lübeck, Germany
Asklepios Klinik Gauting
🇩🇪München-Gauting, Germany
General Hospital "G.Papanikolaou"
🇬🇷Asvestochori, Greece
Uoa Sotiria Hospital
🇬🇷Athens, Greece
Metropolitan General Hospital
🇬🇷Cholargos, Greece
Univ General Hosp Heraklion
🇬🇷Heraklion, Greece
Orszagos Koranyi TBC es Pulmonologiai Intezet
🇭🇺Budapest, Hungary
Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rend.Int.
🇭🇺Szolnok, Hungary
Tudogyogyintezet Torokbalint
🇭🇺Torokbalint, Hungary
AORN Ospedali dei Colli Ospedale Monaldi
🇮🇹Napoli, Campania, Italy
AUSL della Romagna
🇮🇹Ravenna, Emilia-Romagna, Italy
IRCCS Istituto Clinico Humanitas
🇮🇹Rozzano, Lombardia, Italy
Azienda Sanitaria Ospedaliera S Luigi Gonzaga
🇮🇹Orbassano, Piemonte, Italy
Irccs Ist. Tumori Giovanni Paolo Ii
🇮🇹Bari, Puglia, Italy
Azienda Ospedaliero-Universitaria ?PoliclinicoVittorio Emanuele?- P.O. G. Rodolico
🇮🇹Catania, Sicilia, Italy
Kindai University Hospital
🇯🇵Osaka, Japan
NHO Kinki-Chuo Chest Medical Center
🇯🇵Osaka, Japan
National Cancer Center Hospital
🇯🇵Tokyo, Japan
IRCCS Istituto Oncologico Veneto (IOV)
🇮🇹Padova, Veneto, Italy
National Cancer Center Hospital East
🇯🇵Chiba, Japan
Kyushu University Hospital
🇯🇵Fukuoka, Japan
Niigata Cancer Center Hospital
🇯🇵Niigata, Japan
Shizuoka Cancer Center
🇯🇵Shizuoka, Japan
The Cancer Institute Hospital of JFCR
🇯🇵Tokyo, Japan
Wakayama Medical University Hospital
🇯🇵Wakayama, Japan
Chungbuk National University Hospital
🇰🇷Cheongju-si, Korea, Republic of
National Cancer Center
🇰🇷Gyeonggi-do, Korea, Republic of
Osaka International Cancer Institute
🇯🇵Osaka, Japan
Saitama Cancer Center
🇯🇵Saitama, Japan
Seoul National University Bundang Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Samsung Changwon Hospital
🇰🇷Gyeongsangnam-do, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Gazi University Medical Faculty
🇹🇷Ankara, Turkey
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul St Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Ulsan University Hosiptal
🇰🇷Ulsan, Korea, Republic of
Maastricht University Medical Center
🇳🇱Maastricht, Netherlands
Erasmus MC
🇳🇱Rotterdam, Netherlands
Auckland City Hospital
🇳🇿Auckland, New Zealand
Szpital Specjalistyczny Podkarpacki O?rodek Onkologiczny
🇵🇱Brzozow, Poland
Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii
🇵🇱Gdansk, Poland
Krakowski Szpital Specjalistyczny im sw.Jana Pawla II
🇵🇱Krakow, Poland
Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie
🇵🇱Olsztyn, Poland
Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy
🇵🇱Otwock, Poland
Wielkopolskie Centrum Pulmonologii i Torakochirurgii w Poznaniu
🇵🇱Poznan, Poland
Principal Military Clinical Hospital n.a. N.N. Burdenko
🇷🇺Moscow, Moskovskaja Oblast, Russian Federation
Blokhin Cancer Research Center
🇷🇺Moscow, Moskovskaja Oblast, Russian Federation
Scientific Research Institute n.a. N.N. Petrov
🇷🇺Saint Petersburg, Sankt Petersburg, Russian Federation
Clinical Center of Serbia
🇷🇸Belgrade, Serbia
Clinical Hospital Center ''Bezanijska Kosa''
🇷🇸Belgrade, Serbia
Institute for Pulmonary Diseases of Vojvodina
🇷🇸Sremska Kamenica, Serbia
National University Hospital
🇸🇬Singapore, Singapore
National Cancer Centre
🇸🇬Singapore, Singapore
Hospital Clinic Barcelona
🇪🇸Barcelona, Spain
Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Clinico Universitario Virgen de la Victoria
🇪🇸Malaga, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Clínico Universitario de Valencia
🇪🇸Valencia, Spain
UniversitätsSpital Zürich
🇨🇭Zürich, Switzerland
Taipei Veterans General Hospital
🇨🇳Taipei City, Taiwan
Hospital Clinico Universitario Lozano Blesa
🇪🇸Zaragoza, Spain
CHUV
🇨🇭Lausanne, Switzerland
National Cheng-Kung University Hospital
🇨🇳Tainan, Taiwan
Chang-Gung Medical Foundation, Linkou Branch
🇨🇳Taoyuan, Taiwan
National Taiwan University Hospital
🇨🇳Zhongzheng Dist., Taiwan
Adana Baskent University Hospital
🇹🇷Adana, Turkey
Ankara University Medical Faculty
🇹🇷Ankara, Turkey
?zmir Medical Park
🇹🇷Izm?r, Turkey
Royal Cornwall Hospital
🇬🇧Truro, United Kingdom
Medipol University Medical Faculty
🇹🇷Istanbul, Turkey
NHS Lothian - Western General Hospital
🇬🇧Edinburgh, United Kingdom
Guys and St Thomas Hospital
🇬🇧London, United Kingdom
Christie Foundation Trust
🇬🇧Manchester, United Kingdom