Clinical Trial Results:
Phase II non-randomized study of Atezolizumab (MPDL3280A) in combination with Carboplatin Plus Pemetrexed in patients who are chemotherapy-naïve and have stage IV non-squamous non-small cell lung cancer with asymptomatic brain metastases (ATEZO-BRAIN)
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Summary
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EudraCT number |
2017-005154-11 |
Trial protocol |
ES |
Global end of trial date |
31 Mar 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
13 Sep 2023
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First version publication date |
13 Sep 2023
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Other versions |
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Summary report(s) |
ATEZO_BRAIN final report |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
GECP17/05
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03526900 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Fundación GECP
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Sponsor organisation address |
Avda. Merididana 358, Barcelona, Spain, 08027
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Public contact |
Eva Pereira, Fundación GECP, +34 934302006, epereira@gecp.org
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Scientific contact |
Eva Pereira, Fundación GECP, +34 934302006, epereira@gecp.org
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
08 Sep 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Mar 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Mar 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the efficacy of atezolizumab combined with CBDCA and pemetrexed in patients with NSCLC and asymptomatic BM based on PFS according to RANO and RECIST v1.1 criteria for brain and systemic disease respectively
To evaluate the safety of atezolizumab combined with CBDCA and pemetrexed in patients with NSCLC and asymptomatic BM based on the NCI CTCAE v4.0
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Jun 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 40
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Worldwide total number of subjects |
40
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EEA total number of subjects |
40
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
30
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From 65 to 84 years |
10
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85 years and over |
0
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Recruitment
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Recruitment details |
Between November 2018 and Desember 2018, a total of 43 patients were enrolled in the study from 15 different sites. | ||||||
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Pre-assignment
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Screening details |
Screening details:Patients who are chemotherapy naïve and have Stage IV non-squamous NSCLC with untreated brain metastases will be enrolled in this study. | ||||||
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Period 1
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Period 1 title |
Overall study (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||
Blinding implementation details |
Not Blinded
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Arms
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Arm title
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Experimental | ||||||
Arm description |
Induction phase: atezolizumab will be given intravenously (iv) at a dose of 1200 mg for 60 minutes on day 1 of each cycle. Subsequent atezolizumab cycles may be administered for 30 minutes, if there were no perfusion-related toxicity. Pemetrexed will be administered at a dose of 500 mg/m2 IV for 15 minutes on day 1 of each cycle. In addition, folic acid, vitamin B12, and dexamethasone 4 mg will be given the day before and the day after treatment with pemetrexed. Carboplatin will be given at a dose with an area under the 5 curve for 30 minutes on day 1 of each cycle, approximately 30 minutes after the pemetrexed infusion is complete. After completing 4 to 6 cycles of Carboplatino plus pemetrexed and atezolizumab, patients will continue with pemetrexed in combination with atezolizumab (maintenance phase) until they have an unacceptable toxicity, progression of the disease, decision of the patient/physician or have Completed 2 years of treatment. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Atezolizumab
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Investigational medicinal product code |
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Other name |
Tecentriq
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Induction (four or six 21-day cycles) : Atezolizumab 1200 mg / iv + carboplatin 5 AUCs + pemetrexed 500 mg/m2
Maintenance (21-day cycles): atezolizumab 1200 mg/iv + pemetrexed 500 mg/m2.
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Baseline characteristics reporting groups
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Reporting group title |
Overall study (overall period)
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Experimental
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Reporting group description |
Induction phase: atezolizumab will be given intravenously (iv) at a dose of 1200 mg for 60 minutes on day 1 of each cycle. Subsequent atezolizumab cycles may be administered for 30 minutes, if there were no perfusion-related toxicity. Pemetrexed will be administered at a dose of 500 mg/m2 IV for 15 minutes on day 1 of each cycle. In addition, folic acid, vitamin B12, and dexamethasone 4 mg will be given the day before and the day after treatment with pemetrexed. Carboplatin will be given at a dose with an area under the 5 curve for 30 minutes on day 1 of each cycle, approximately 30 minutes after the pemetrexed infusion is complete. After completing 4 to 6 cycles of Carboplatino plus pemetrexed and atezolizumab, patients will continue with pemetrexed in combination with atezolizumab (maintenance phase) until they have an unacceptable toxicity, progression of the disease, decision of the patient/physician or have Completed 2 years of treatment. | ||
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End point title |
Progression Free Survival at 12 weeks [1] | ||||||||||
End point description |
Rate of PFS at 12 weeks after enrollment defined as the rate of patients free of disease progression (intracranial or systemic) or death from any cause whichever occurs first at 12 weeks as determined by the investigator according to RANO and RECIST v1.1. criteria for brain and systemic disease respectively.
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End point type |
Primary
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End point timeframe |
At 12 weeks from initiation of treatment
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Safety and efficacy were assessed in the intention-to-treat population cohort of 40 patients using the Bayesian Multc Lean design. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Best response (Intracranial) | ||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Defined as a complete response or partial response, stable response or progression, on two consecutive evaluations 6 weeks apart, as determined by the investigator according to RANO and RECIST v1.1 criteria for brain and systemic disease respectively.
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| Notes [2] - Intracranial |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Best response (Systemic) | ||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Defined as a complete response , partial response, stables response, progression on two consecutive evaluations 6 weeks apart, as determined by the investigator according to RANO and RECIST v1.1 criteria for systemic disease respectively.
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Overall Survivall (OS) | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Overall Survival (OS) is defined as the time, in months, from the inclusion date to the death date. A patient is censored at the last contact date if he/she does not die.
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Any adverse event or breakdown occurring during the course of the study.
The investigator will have to collect all adverse events once they have signed informed consent, during treatment and 30 days after the last dose study treatment administration.
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Adverse event reporting additional description |
The severity of AE will be determined using CTCAE version 4.0.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
12.0
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Reporting groups
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Reporting group title |
Subjects per protocol
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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05 Dec 2019 |
Changes in the protocol: due to the new version of the IB of Atezolizumab v15. The management guidelines for immune-mediated effects are changed.
In addition, other changes are made to the protocol to update different aspects of study management. |
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12 Mar 2021 |
Changes in the protocol: The information contained in the protocol regarding the analyzes to be carried out in the brain magnetic resonance imaging (MRI) of the patients included in the study is reviewed. A new translational analysis of the study MRIs is added to identify neuroimaging radiomic markers that predict intracranial response to study systemic anticancer therapy. This new analysis may contribute to a better understanding of the clinical evolution of patients with lung cancer by obtaining predictions of the results of possible treatments. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/37603816 |
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