A Phase III Clinical Study to Evaluate the Efficacy and Safety of Atezolizumab in Combination with Carboplatin+Paclitaxel or Atezolizumab in Combination with Carboplatin+Nab-Paclitaxel Compared with Carboplatin+Nab-Paclitaxel in Patients with Stage IV Squamous Non-Small Cell Lung Cancer

• Register: EUCTR
• Last refreshed on: 8 March 2021
• Main ID: EUCTR2014-003208-59-LV
• Date of registration: 21/04/2015
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A Phase III Clinical Study to Evaluate the Efficacy and Safety of Atezolizumab in Combination with Carboplatin+Paclitaxel or Atezolizumab in Combination with Carboplatin+Nab-Paclitaxel Compared with Carboplatin+Nab-Paclitaxel in Patients with Stage IV Squamous Non-Small Cell Lung Cancer
• Scientific title: A PHASE III, OPEN-LABEL, MULTICENTER, RANDOMIZED STUDY EVALUATING THE EFFICACY AND SAFETY OF ATEZOLIZUMAB (MPDL3280A, ANTI-PD-L1 ANTIBODY) IN COMBINATION WITH CARBOPLATIN+PACLITAXEL OR ATEZOLIZUMAB IN COMBINATION WITH CARBOPLATIN+NAB-PACLITAXEL VERSUS CARBOPLATIN+NAB-PACLITAXEL IN CHEMOTHERAPY-NAIVE PATIENTS WITH STAGE IV SQUAMOUS NON-SMALL CELL LUNG CANCER
• Date of first enrolment: 11/05/2015
• Target sample size: 1025
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-003208-59
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, France, Germany, Israel, Italy, Japan, Latvia, Lithuania, Mexico, Netherlands, Peru, Portugal, Russian Federation, Singapore, Slovakia, Spain, Sweden, Switzerland, Taiwan, Ukraine, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: Genentech Inc. c/o F. Hoffmann La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: Genentech Inc. c/o F. Hoffmann La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
• Eastern Cooperative Oncology Group performance status of 0 or 1
• Histologically or cytologically confirmed Stage IV squamous NSCLC
Patients with tumors of mixed histology (squamous and non-squamous) are eligible if the major histological component appears to be squamous.
• No prior treatment for Stage IV squamous NSCLC
Patients known to have a sensitizing mutation in the epidermal growth factor receptor (EGFR) gene must have experienced disease progression (during or after treatment) or intolerance to treatment with one or more EGFR tyrosine kinase inhibitor (TKIs), such as erlotinib, gefitinib, or another EGFR TKI appropriate for the treatment of EGFR-mutant NSCLC.
Patients with unknown EGFR mutation status do not require testing.
Patients known to have an anaplastic lymphoma kinase (ALK) fusion oncogene must have experienced disease progression (during or after treatment) or intolerance to treatment with one or more ALK inhibitors (i.e., crizotinib) appropriate for the treatment of NSCLC in patients having an ALK fusion oncogene.
Patients with unknown ALK mutation status do not require testing.
• Patients who have received prior neo-adjuvant, adjuvant chemotherapy, radiotherapy, 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 chemotherapy, radiotherapy, or chemoradiotherapy.
• Measurable disease, as defined by RECIST v1.1


Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 720
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 305

Exclusion criteria:
• Active or untreated CNS metastases as determined by CT or 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 > 2 weeks prior to randomization
• Leptomeningeal disease
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Positive test for HIV
All patients will be tested for HIV prior to inclusion into the study; patients who test positive for HIV will be excluded from the clinical.
• Uncontrolled tumor-related pain
• Uncontrolled or symptomatic hypercalcemia
• Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
• Known tumor PD-L1 expression status from other clinical trials
• Women who are pregnant, lactating, or intending to become pregnant during the study
• Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
• History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
• Patients with active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C
• Active tuberculosis
• Severe infections within 4 weeks prior to randomization, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
• Received therapeutic oral or IV antibiotics within 2 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
• Major surgical procedure other than for diagnosis within 28 days prior to randomization or anticipation of need for a major surgical procedure during the course of the study
• Prior allogeneic bone marrow transplantation or solid organ transplant
• Administration of a live, attenuated vaccine within 4 weeks before randomization or anticipation that such a live attenuated vaccine will be required during the study
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

SQUAMOUS NON-SMALL CELL LUNG CANCER
MedDRA version: 20.0 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: MPDL3280A-RO5541267-F-03
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Not Yet defined
Current Sponsor code: RO5541267
Other descriptive name: MPDL3280A
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-

Trade Name: Abraxane
Product Name: nab-paclitaxel
Product Code: RO024-7506
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: PACLITAXEL
CAS Number: 33069-62-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Trade Name: Tarceva (Erlotinib)
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ERLOTINIB
CAS Number: 183321-74-6
Current Sponsor code: Ro 50-8231
Other descriptive name: erlotinib hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Trade Name: Tecentriq
Product Name: MPDL3280A-RO5541267-F-03
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Not Yet defined
Current Sponsor code: RO5541267
Other descriptive name: MPDL3280A
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-

Primary Outcome(s)

Main Objective: •To evaluate the efficacy of atezolizumab as measured by investigator-assessed progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in the tumor gene expression (tGE) population and the intent-to-treat (ITT) population
•To evaluate the efficacy of atezolizumab as measured by overall survival (OS) in the ITT population

Secondary Objective: •To evaluate the efficacy of atezolizumab as measured by:
oOS in the tGE population
oInvestigator-assessed PFS according to RECIST v1.1 and OS in the TC2/3 or IC2/3 population and the TC1/2/3 or IC1/2/3 population
oInvestigator-assessed ORR and DOR according to RECIST v1.1 in the tGE population and the ITT population
•To evaluate the OS rate at 1 and 2 years in each treatment arm for the tGE and the ITT population
•To determine the impact of atezolizumab as measured by time to deterioration (TTD) and change from baseline in patient-reported lung cancer symptoms
•To evaluate the efficacy of the treatment regimen of atezolizumab+carboplatin+paclitaxel versus atezolizumab+carboplatin+nab-paclitaxel as measured by investigator-assessed PFS according to RECIST v1.1 and OS in the tGE population and the ITT population

Timepoint(s) of evaluation of this end point: 1.Time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first
2.Time from randomization to death from any cause

Primary end point(s): 1.PFS, defined as the time from randomization to the first occurrence of the disease progression as determined by the investigator using RECIST v1.1 or death from any cause, whichever occurs first, in the tGE population and ITT population
2.OS, defined as the time from randomization to death from any cause, in the ITT population

Secondary Outcome(s)

Secondary end point(s): 1.OS in the tGE population
2.PFS, as determined by the investigator according to RECIST v1.1, and OS in the TC2/3 or IC2/3 population and the TC1/2/3 or IC1/2/3 population
3.Objective response, defined as partial response (PR) or complete response (CR) as determined by the investigator according to RECIST v1.1 in the tGE population and ITT population
4. DOR, defined as the time 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 occurs first, in the tGE population and ITT population
5.PFS, as determined by the investigator according to RECIST v1.1, and OS in the two atezolizumab-containing arms in the tGE population and the ITT population
6.OS rate at 1 and 2 years in each treatment arm for the tGE population and the ITT population
7.TTD in patient-reported lung cancer symptoms, defined as time from randomization to deterioration (10-point change) on each of the EORTC QLQ-C30 and EORTC QLQ-LC13 symptom subscales (cough, dyspnea [single item], dyspnea, chest pain, and arm/shoulder pain) in the tGE population and ITT population
8.Change from baseline in patient-reported lung cancer symptoms (cough, dyspnea, and chest pain) on the symptom severity score of the SILC scale in the tGE population and ITT population

Timepoint(s) of evaluation of this end point: 1. Time from randomization to death from any cause
2 and 5. Time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first
3. To be analysed at the time of the primary analysis
4. Time interval from the date of the first occurrence of a complete or partial response until the first date that progressive disease or death is documented, whichever occurs first
6. At 1 and 2 years
7. Time from randomization to deterioration
8. Baseline and survival follow-up (every 3 months after disease progression or loss of clinical benefit)

Secondary ID(s)

GO29437

2014-003208-59-IT

Source(s) of Monetary Support

F. Hoffmann - La Roche Ltd

Ethics review

Status: Approved
Approval date: 24/04/2015
Contact:

Results

• Results available: Yes
• Date Posted: 13/10/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-003208-59/results