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A Study of Atezolizumab in Combination With Carboplatin or Cisplatin + Pemetrexed Compared With Carboplatin or Cisplatin + Pemetrexed in Participants Who Are Chemotherapy-Naive and Have Stage IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC) (IMpower 132)

This study is currently recruiting participants.
Verified August 2017 by Hoffmann-La Roche
Sponsor:
ClinicalTrials.gov Identifier:
NCT02657434
First Posted: January 15, 2016
Last Update Posted: August 2, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Hoffmann-La Roche
  Purpose
This is a randomized, Phase III, multicenter, open-label study designed to evaluate the safety and efficacy of atezolizumab in combination with cisplatin or carboplatin + pemetrexed compared with treatment with cisplatin or carboplatin + pemetrexed in participants who are chemotherapy-naive and have Stage IV non-squamous NSCLC. Eligible participants will be randomized by a 1:1 ratio into 2 groups: Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed) and Arm B (Carboplatin or Cisplatin + Pemetrexed). The study will be conducted in two phases: Induction Phase and Maintenance Phase.

Condition Intervention Phase
Non-Small Cell Lung Cancer Drug: Atezolizumab Drug: Carboplatin Drug: Cisplatin Drug: Pemetrexed Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III, Open-Label, Randomized Study of Atezolizumab (MPDL3280A, Anti-Pd-L1 Antibody) in Combination With Carboplatin or Cisplatin + Pemetrexed Compared With Carboplatin or Cisplatin + Pemetrexed in Patients Who Are Chemotherapy-Naive and Have Stage IV Non-Squamous Non-Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Progression Free Survival (PFS) as Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [ Time Frame: Baseline then every 6 weeks for 12 months after Cycle (Cy;length=21 days) 1 Day (D) 1;every 9 weeks until radiographic disease progression, consent withdrawal, death, or study termination by Sponsor, whichever occurs first (up to approximately 44 months) ]
  • Overall Survival [ Time Frame: Baseline then every 6 weeks for 12 weeks following Cy1D1 (Cy length=21 days) & then every 9 weeks until death (up to approximately [app] 44 months) ]

Secondary Outcome Measures:
  • Percentage of Participants Who Survived at Year 1 [ Time Frame: Year 1 ]
  • Percentage of Participants Who Survived at Year 2 [ Time Frame: Year 2 ]
  • Percentage of Participants With an Objective Response (Complete Response [CR] or Partial Response [PR]) Assessed by the Investigator Using RECIST V1.1 [ Time Frame: Baseline then every 6 weeks for 12 months following Cy1D1 (Cy length=21 days) thereafter every 9 weeks until radiographic disease progression, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first (up to app 44 months) ]
  • Duration of Response as Determined by the Investigator Using RECIST v1.1 [ Time Frame: Baseline then every 6 weeks for 12 months following Cy1D1 (Cy length=21 days) thereafter every 9 weeks until radiographic disease progression, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first (up to app 44 months) ]
  • Time to Response as Determined by the Investigator According to RECIST v1.1 [ Time Frame: Baseline then every 6 weeks for 12 months following Cy1D1 (Cy length=21 days) thereafter every 9 weeks until radiographic disease progression, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first (up to app 44 months) ]
  • PFS as Determined by the Independent Review Facility Using RECIST V1.1 [ Time Frame: Baseline then every 6 weeks for 12 months following Cy1D1 (Cy length=21 days) thereafter every 9 weeks until radiographic disease progression, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first (up to app 44 months) ]
  • Time in Response as Determined by the Investigator Using RECIST V1.1 [ Time Frame: Baseline then every 6 weeks for 12 months following Cy1D1 (Cy length=21 days) thereafter every 9 weeks until radiographic disease progression, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first (up to app 44 months) ]
  • Time to Deterioration in Patient-Reported Lung Cancer Symptoms as Assessed by European Organization for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core 30 (QLQ-C30) Symptom Score [ Time Frame: Baseline up to 3 and 6 months after disease progression or loss of clinical benefit (up to app 44 months) ]
  • Time to Deterioration in Patient-Reported Lung Cancer Symptoms as Assessed by EORTC Quality-of-Life Lung Cancer Module (QLQ-LC13) Symptom Score [ Time Frame: Baseline up to 3 and 6 months after disease progression or loss of clinical benefit (up to approximately 44 months) ]
  • Time to Deterioration in Patient-Reported Lung Cancer Symptoms as Reported Using the Symptoms in Lung Cancer (SILC) Scale Score [ Time Frame: Baseline up to 3 and 6 months after disease progression or loss of clinical benefit (up to app 44 months) ]
  • Minimum Observed Serum Atezolizumab Concentration (Cmin) Prior to Infusion [ Time Frame: Predose (Prd; 0 hour [h]) on D1 of Cy1,2,3,4,8,16 (Cy length=21 days) and thereafter on D1 of every 8th cycle (up to app 44 months) ]
  • Maximum Observed Serum Atezolizumab Concentration (Cmax) Prior to Infusion [ Time Frame: Prd (0h) on D1 of Cy1,2,3,4,8,16 (Cy length=21 days)&thereafter on D1 of every 8th cy; 0.5h post infusion (infusion duration=1h) on Cy1D1;at treatment discontinuation &then every 30 days (up to 120 days) after atezolizumab last dose (up to app 44 months) ]
  • Plasma Concentrations for Carboplatin in Arm A(Atezolizumab + Carboplatin or Cisplatin + Pemetrexed) [ Time Frame: Prd (0 h), 5-10 minutes (mins) before end of carboplatin infusion (infusion duration=1-2 h), 1 h post-infusion on D1 of Cy1,3 (Cy length=21 days) ]
  • Plasma Concentrations for Cisplatin in Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed) [ Time Frame: Prd (0 h), 5-10 mins before end of cisplatin infusion (infusion duration=30-60 mins), 1 h post-infusion on D1 of Cy1,3 (Cy length=21 days) ]
  • Plasma Concentrations for Pemetrexed in Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed) [ Time Frame: Prd (0 h), 5-10 mins before end of pemetrexed infusion (infusion duration=10 mins), 1 h post-infusion on D1 of Cy1,3 (Cy length=21 days) ]
  • Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) of Atezolizumab [ Time Frame: Prd (0 h) on D1 of Cy1,2,3,4,8,16 (Cy length=21 days) and thereafter on D1 of every 8th cycle, at treatment discontinuation & then every 30 days (up to 120 days) after last dose of atezolizumab (up to app 44 months) ]

Estimated Enrollment: 568
Actual Study Start Date: April 30, 2016
Estimated Study Completion Date: November 30, 2019
Estimated Primary Completion Date: November 30, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed
Participants will receive intravenous (IV) infusion of 1200 milligrams (mg) of atezolizumab on Day 1 every 3 weeks (q3w), IV infusion of 500 milligrams per meter square (mg/m^2) pemetrexed on Day 1 q3w, and as per investigator's choice either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain area under concentration versus time (AUC) = 6 milligrams per milliliter per minute (mg/mL/min) or IV infusion of 75 mg/m^2 cisplatin q3w on Day 1 q3w, during induction dosing period of 4 or 6 cycles (Cycle length=21 days). Participants who experience clinical benefit during the induction phase will begin maintenance therapy. Participants will receive IV infusion of 1200 mg of atezolizumab and 500 mg/m^2 of pemetrexed on Day 1 q3w until disease progression in the maintenance period.
Drug: Atezolizumab
Participants will receive IV infusion of 1200 mg atezolizumab on Day 1 q3w for 4 or 6 cycles (Cycle length=21 days) in induction dosing period and until disease progression on Day 1 q3w in the maintenance dosing period.
Other Name: MPDL3280A; TECENTRIQ
Drug: Carboplatin
Participants will receive IV infusion of carboplatin on Day 1 q3w for 4 or 6 cycles (Cycle length=21 days) in induction dosing period with doses calculated using Calvart formula.
Drug: Cisplatin
Participants will receive IV infusion of 75 mg/m^2 cisplatin on Day 1 q3w for 4 or 6 cycles (Cycle length=21 days) in induction dosing period.
Drug: Pemetrexed
Participants will receive IV infusion of 500 mg/m^2 pemetrexed on Day 1 q3w for 4 or 6 cycles (Cycle length=21 days) in induction dosing period and until disease progression on Day 1 q3w in the maintenance dosing period.
Active Comparator: Arm B (Carboplatin or Cisplatin + Pemetrexed)
Participants will receive IV infusion of 500 mg/m^2 pemetrexed on Day 1 q3w, and as per investigator's choice of either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain AUC =6 mg/mL/min or IV infusion of 75 mg/m^2 cisplatin q3w on Day 1 q3w, during induction dosing period for 4 or 6 cycles (Cycle length=21 days). Participants who do not experience disease progression during the induction phase will begin maintenance therapy. Participants will receive IV infusion of 500 mg/m^2 of pemetrexed on Day 1 q3w until disease progression in the maintenance period.
Drug: Carboplatin
Participants will receive IV infusion of carboplatin on Day 1 q3w for 4 or 6 cycles (Cycle length=21 days) in induction dosing period with doses calculated using Calvart formula.
Drug: Cisplatin
Participants will receive IV infusion of 75 mg/m^2 cisplatin on Day 1 q3w for 4 or 6 cycles (Cycle length=21 days) in induction dosing period.
Drug: Pemetrexed
Participants will receive IV infusion of 500 mg/m^2 pemetrexed on Day 1 q3w for 4 or 6 cycles (Cycle length=21 days) in induction dosing period and until disease progression on Day 1 q3w in the maintenance dosing period.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Histologically or cytologically confirmed, Stage IV non-squamous NSCLC. Participants with tumors of mixed non-small cell histology (i.e., squamous and non-squamous) are eligible if the major histological component appears to be non-squamous
  • No prior treatment for Stage IV non-squamous NSCLC. Participants with a sensitizing mutation in the epidermal growth factor receptor (EGFR) gene or with an anaplastic lymphoma kinase (ALK) fusion oncogene are excluded. Participants with unknown EGFR and ALK status require test results at screening from a local or central laboratory
  • Participants who have received prior neo-adjuvant, radiotherapy, adjuvant chemotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from randomization since the last dose of chemotherapy and/or radiotherapy
  • Participants should submit a pre-treatment tumor tissue sample if available before or within 4 weeks after enrollment. If tumor tissue is not available, participants are still eligible
  • For enrollment into the China extension phase, residence in the People's Republic of China
  • Measurable disease, as defined by RECIST v1.1
  • Adequate hematologic and end organ function
  • For women of childbearing potential: agreement to remain abstinent or use contraceptive methods that result in a failure rate of less than (<) 1 percent (%) per year during the treatment period and for at least 5 months after the last dose of atezolizumab or 6 months after the last dose of cisplatin
  • For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm

Exclusion Criteria:

Cancer-Specific Exclusions

  • Participants with a sensitizing mutation in the EGFR gene or an ALK fusion oncogene
  • Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
  • Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for greater than or equal to (>= 2) weeks prior to randomization
  • Leptomeningeal disease
  • Uncontrolled tumor-related pain
  • Uncontrolled or symptomatic hypercalcemia (greater than [>] 1.5 millimole/Liter ionized calcium or calcium >12 milligrams/deciliter or corrected serum calcium >upper limit of normal)
  • Malignancies other than NSCLC within 5 years prior to randomization
  • Known tumor programmed death-ligand 1 (PD-L1) expression status from other clinical studies (e.g., participants whose PD-L1 expression status was determined during screening for entry into a study with anti-PD-1 or anti-PD L1 antibodies but were not eligible are excluded)

General Medical Exclusions:

  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • History of certain autoimmune disease
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis
  • All participants will be tested for human immunodeficiency virus (HIV) prior to the inclusion into the study and HIV-positive participants will be excluded from the clinical study
  • Severe infections within 4 weeks prior to randomization
  • Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction or cerebrovascular accident within 3 months prior to randomization, unstable arrhythmias, or unstable angina
  • Illness or condition that may interfere with a participant's capacity to understand, follow, and/or comply with study procedures

Exclusion Criteria Related to Medications and Chemotherapy:

  • Prior treatment with EGFR inhibitors or ALK inhibitors
  • Any approved anti-cancer therapy, including hormonal therapy within 21 days prior to initiation of study treatment
  • Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, anti-PD-1, and anti-PD-L1 therapeutic antibodies
  • Treatment with systemic immunostimulatory agents within 4 weeks prior to randomization
  • Treatment with systemic immunosuppressive medications

Exclusion Criteria Related to Chemotherapy:

  • History of allergic reactions to cisplatin, carboplatin, or other platinum-containing compounds
  • Participants with hearing impairment (cisplatin)
  • Grade >=2 peripheral neuropathy as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria (cisplatin)
  • Creatinine clearance (CRCL) <60 milliliters/minute (mL/min) for cisplatin or <45 mL/min for carboplatin
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02657434


Contacts
Contact: Reference Study ID Number: GO29438 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

  Show 244 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02657434     History of Changes
Other Study ID Numbers: GO29438
2015-003605-42 ( EudraCT Number )
First Submitted: January 14, 2016
First Posted: January 15, 2016
Last Update Posted: August 2, 2017
Last Verified: August 2017

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Atezolizumab
Cisplatin
Carboplatin
Pemetrexed
Antibodies, Monoclonal
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Immunologic Factors
Physiological Effects of Drugs