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A Study of Carboplatin Plus Etoposide With or Without Atezolizumab in Participants With Untreated Extensive-Stage (ES) Small Cell Lung Cancer (SCLC) (IMpower133)

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ClinicalTrials.gov Identifier: NCT02763579
Recruitment Status : Active, not recruiting
First Posted : May 5, 2016
Results First Posted : June 13, 2019
Last Update Posted : June 19, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE May 4, 2016
First Posted Date  ICMJE May 5, 2016
Results First Submitted Date  ICMJE April 19, 2019
Results First Posted Date  ICMJE June 13, 2019
Last Update Posted Date June 19, 2019
Actual Study Start Date  ICMJE June 7, 2016
Actual Primary Completion Date April 24, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 21, 2019)
  • Duration of Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1 [ Time Frame: 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) [ Time Frame: Baseline until death from any cause (up to approximately 23 months) ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 4, 2016)
  • Duration of Overall Survival [ Time Frame: Baseline until death from any cause (up to approximately 37 months) ]
  • Duration of Progression-Free Survival as Assessed by Investigator Using RECIST v1.1 [ Time Frame: Baseline until disease progression or death, whichever occurred first (up to approximately 37 months) ]
Change History Complete list of historical versions of study NCT02763579 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 21, 2019)
  • Percentage of Participants With Objective Response (OR) as Assessed by the Investigator Using RECIST v1.1 [ Time Frame: Baseline until partial response (PR) or complete response (CR), whichever occurs first (up to approximately 46 months) ]
  • Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1 [ Time Frame: First occurrence of PR or CR until PD or death, whichever occurs first (up to approximately 46 months) ]
  • Percentage of Participants Alive and Without PD, as Assessed by the Investigator Using RECIST v1.1, at 6 Months and 1 Year [ Time Frame: 6 months, 1 year (up to approximately 46 months) ]
  • Percentage of Participants Alive at 1 Year and 2 Years [ Time Frame: 1 year, 2 years (up to approximately 46 months) ]
  • Time to Deterioration (TTD) Per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core 30 (C30) Score [ Time Frame: Baseline until deterioration per symptom subscale (up to approximately 46 months) ]
  • TTD Per EORTC QLQ Lung Cancer Module (LC13) Score [ Time Frame: Baseline until deterioration per symptom subscale (up to approximately 46 months) ]
  • Percentage of Participants With Adverse Events [ Time Frame: Baseline until up to 90 days after end of treatment (up to approximately 46 months) ]
  • Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) [ Time Frame: 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 46 months) and 120 days after last dose (up to approximately 46 months overall) ]
  • Maximum Observed Serum Concentration (Cmax) of Atezolizumab [ Time Frame: Predose (0 H) and postdose (0.5 H) on D1 of C1; predose (0 H) on D1 of C2, 3, 4, 8, 16, and Q8C thereafter (cycle = 21 days) until treatment discontinuation (up to 46 months) and 120 days after last dose (up to approximately 46 months overall) ]
    Atezolizumab infusion duration is 60 minutes for the first infusion and 30 minutes for subsequent infusions.
  • Minimum Observed Serum Concentration (Cmin) of Atezolizumab [ Time Frame: Predose (0 H) on D1 of C1, 2, 3, 4, 8, 16, and Q8C thereafter (cycle = 21 days) until treatment discontinuation (up to 46 months) and 120 days after last dose (up to approximately 46 months overall) ]
    Atezolizumab infusion duration is 60 minutes for the first infusion and 30 minutes for subsequent infusions.
  • Plasma Concentration of Carboplatin [ Time Frame: Predose (0 H) and 5-10 minutes before end/1 H after end of carboplatin infusion (infusion duration = 1 H) on D1 of C1 and C3 (cycle = 21 days)(up to approximately 46 months) ]
  • Plasma Concentration of Etoposide [ Time Frame: Predose (0 H) and 5-10 minutes before end/1 H and 4H after end of etoposide infusion (infusion duration = 1 H) on D1 of C1 and C3 (cycle = 21 days)(up to approximately 46 months) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 4, 2016)
  • Number of Participants With Objective Response as Assessed by the Investigator Using RECIST v1.1 [ Time Frame: Baseline until partial response (PR) or complete response (CR) (up to approximately 37 months) ]
  • Duration of Response as Assessed by the Investigator Using RECIST v1.1 [ Time Frame: First occurrence of PR or CR until disease progression or death, whichever occurred first (up to approximately 37 months) ]
  • Time in Response as Assessed by the Investigator Using RECIST v1.1 [ Time Frame: Baseline until disease progression or death, whichever occurred first (up to approximately 37 months) ]
  • Progression-Free Survival at 6 Month and 1 Year, as Assessed by Investigator Using RECIST v1.1 [ Time Frame: 6 Month and 1 Year ]
  • Overall Survival at 6 Month and 1 Year [ Time Frame: 6 Month and 1 Year ]
  • Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score [ Time Frame: Baseline, up to approximately 37 months ]
  • Change From Baseline in EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) Score [ Time Frame: Baseline, up to approximately 37 months ]
  • Number of Participants with Adverse Events [ Time Frame: up to 90 days after end of treatment (approximately up to 37 months) ]
  • Number of Participants With Anti-Therapeutic Antibodies (ATA) [ Time Frame: Pre-dose (PrD) on Day (D) 1 of each treatment cycle (C (C length=21 days) until treatment discontinuations (up to approximately 37 months [Mo]), 120 days after last dose (up to approximately 37 Mo overall) ]
  • Maximum Observed Serum Atezolizumab Concentration (Cmax) [ Time Frame: PrD) 0.5 hours post-dose on C1D1, PrD on D1 of C2, 3, 4, 8, 16, then PrD on D1 of every eighth cycle until treatment discontinuation (up to approximately 37 Mo), 120 days after last dose (up to approximately 37 Mo overall) (each C length=21 days) ]
  • Minimum Observed Serum Atezolizumab Concentration (Cmin) [ Time Frame: PrD on D1 of C1, 2, 3, 4, 8, 16, then every eighth cycle until treatment discontinuation (up to approximately 37 Mo), 120 days after last dose (up to approximately 37 Mo overall) (each C length=21 days) ]
  • Maximum Observed Plasma Carboplatin Concentration [ Time Frame: PrD, 5-10 minutes before the end of carboplatin infusion (infusion duration=1 hour), and 1 hour after the end of carboplatin infusion (infusion duration=1 hour) on C1D1 and C3D1 (each cycle length=21 days) ]
  • Maximum Observed Plasma Etoposide Concentration\n [ Time Frame: PrD, 5-10 minutes before the end of etoposide infusion (infusion duration=1 hour), and 1, 4 hour after the end of etoposide infusion (infusion duration=1 hour) on C1D1 and C3D1 (each cycle length=21 days) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Carboplatin Plus Etoposide With or Without Atezolizumab in Participants With Untreated Extensive-Stage (ES) Small Cell Lung Cancer (SCLC)
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Small Cell Lung Carcinoma
Intervention  ICMJE
  • 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).
    Other Name: MPDL3280A, RO5541267, Tecentriq
  • 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).
  • 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).
  • 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).
Study Arms  ICMJE
  • Experimental: 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.
    Interventions:
    • Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
    • Drug: Carboplatin
    • Drug: Etoposide
  • Active Comparator: 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.
    Interventions:
    • Drug: Carboplatin
    • Drug: Etoposide
    • Drug: Placebo
Publications * Horn L, Mansfield AS, Szczęsna 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 21, 2019)
403
Original Estimated Enrollment  ICMJE
 (submitted: May 4, 2016)
400
Estimated Study Completion Date  ICMJE March 24, 2020
Actual Primary Completion Date April 24, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Brazil,   Chile,   China,   Czechia,   France,   Germany,   Greece,   Hong Kong,   Hungary,   Italy,   Japan,   Korea, Republic of,   Mexico,   Poland,   Russian Federation,   Serbia,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02763579
Other Study ID Numbers  ICMJE GO30081
2015-004861-97 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP