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NCT Number: NCT02763579

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

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.

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Key information

Conditions

Small Cell Lung Carcinoma Bronchial Neoplasms Carcinoma, Bronchogenic Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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

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).

Other names: MPDL3280A, RO5541267, Tecentriq

carboplatin

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

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

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).

Primary outcomes

  1. Duration of Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1 in the Global Population

    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).

  2. Duration of Overall Survival (OS) in the Global Population

    Time frame: 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 outcomes

  1. Percentage of Participants With Objective Response Rate (ORR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population

    Time frame: 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.

  2. Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population

    Time frame: 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.

  3. PFS Rate at 6 Months and at 1 Year in Global Population

    Time frame: 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.

  4. OS Rate at 1 Year and 2 Years in the Global Population

    Time frame: 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.

  5. 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

    Time frame: 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.

  6. Percentage of Participants With at Least One Adverse Event in the Global Population

    Time frame: 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.

  7. Percentage of Participants With Anti-Drug Antibodies (ADA) to Atezolizumab in the Global Population

    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 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.

  8. Maximum Observed Serum Concentration (Cmax) of Atezolizumab in the Global Population

    Time frame: 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.

  9. Minimum Observed Serum Concentration (Cmin) of Atezolizumab in the Global Population

    Time frame: 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.

  10. Plasma Concentration of Carboplatin in the Global Population

    Time frame: 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.

  11. Plasma Concentration of Etoposide in the Global Population

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study 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

Acronym: IMpower133

Important dates

Study start
2016
Primary completion
2018
Study completion
2022
First posted
May 5, 2016
Registry last updated
Jul 28, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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