Carcinoma, Non-Small-Cell Lung
Conditions
Brief summary
The objectives of this single-arm, open-label trial are to assess the efficacy and safety of afatinib as second line treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harbouring a common EGFR mutation who have failed first-line platinum-based chemotherapy and to demonstrate that the efficacy and safety are comparable to the results seen in previous trials.
Interventions
DRUGAfatinib
Afatinib tablet once daily until progression
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Pathologically confirmed diagnosis of Stage IIIB (with cytologically proven pleural effusion or pericardial effusion) or Stage IV adenocarcinoma of the lung. Patients with mixed histology are eligible if adenocarcinoma is the predominant histology. 2. Documented EGFR mutation (L858R and/or Deletion 19) with no other known EGFR mutation. 3. Measureable disease according to RECIST 1.1. 4. Radiologically confirmed progression or recurrence of disease during or following first line therapy with a platinum-based chemotherapy regimen. 5. Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1. 6. Adequate organ function.
Exclusion criteria
1. More than one line of prior therapy for disease. 2. Previously received less than 3 cycles of platinum-based chemotherapy due to toxicity and/or intolerance of treatment. 3. Previous treatment with any EGFR targeting Tyrosine Kinase Inhibitor (TKI) or antibody. 4. Known pre-existing interstitial lung disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Tumour Response (Complete Response [CR], Partial Response [PR]) as Assessed by the Investigator According to the RECIST Version 1.1 | Post baseline tumour-imaging was performed at every 8 weeks until Week 56 and then every 12 weeks; up to 802 days | As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by Magnetic resonance imaging (MRI): Complete Response (CR), disappearance of all target lesions; Partial Response (PR), =30% decrease in the sum of the longest diameter of target lesions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) as Assessed by the Investigator According to RECIST 1.1. | Post baseline tumour-imaging was performed at every 8 weeks until Week 56 and then every 12 weeks; up to 802 days | Progression-free survival (PFS) is the time from treatment start to disease progression (or death if the patient died before progression). PFS as assessed based on investigator review according to the response evaluation criteria in solid tumours (RECIST) version 1.1. |
| Disease Control (CR, PR, Stable Disease [SD]) as Assessed by the Investigator According to RECIST 1.1 | Post baseline tumour-imaging was performed at every 8 weeks until Week 56 and then every 12 weeks; up to 802 days | As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), =30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. |
Countries
Egypt, Malaysia, Philippines, Poland, Romania, Serbia, Thailand
Participant flow
Recruitment details
An open-label, single-arm phase IV study to assess the efficacy and safety of Afatinib as second-line therapy for patients with locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) harbouring an Epidermal Growth Factor Receptor(EGFR) mutation (Del19 or L858R) who have failed first-line treatment with platinum-based chemotherapy.
Pre-assignment details
All patients were screened for eligibility to participate in the trial. Subjects attended specialist sites which would then ensure that all subjects met all inclusion/exclusion criteria. Subjects were not to be entered to trial treatment if any one of the specific entry criteria were not met.
Participants by arm
| Arm | Count |
|---|---|
| Afatinib 40 mg All patients received continuous daily treatment with Afatinib at a starting dose of 40 milligram (mg), treatment interruption and reduction scheme to 30 mg and then to 20 mg were permitted to manage treatment-related adverse events (AEs). Patients were orally administered with the film coated tablet once a day without food. | 60 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 12 |
| Overall Study | Clinical symptoms of progression | 2 |
| Overall Study | Progression disease according to RECIST | 24 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Switched to commercial afatinib | 20 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Afatinib 40 mg |
|---|---|
| Age, Continuous | 59.9 Years STANDARD_DEVIATION 9.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 19 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 41 Participants |
| Sex: Female, Male Female | 33 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 11 / 60 |
| other Total, other adverse events | 56 / 60 |
| serious Total, serious adverse events | 21 / 60 |
Outcome results
Primary
Objective Tumour Response (Complete Response [CR], Partial Response [PR]) as Assessed by the Investigator According to the RECIST Version 1.1
As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by Magnetic resonance imaging (MRI): Complete Response (CR), disappearance of all target lesions; Partial Response (PR), =30% decrease in the sum of the longest diameter of target lesions
Time frame: Post baseline tumour-imaging was performed at every 8 weeks until Week 56 and then every 12 weeks; up to 802 days
Population: Treated Set (TS): The TS includes all patients who were documented to have taken at least 1 dose of afatinib.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Afatinib 40 mg | Objective Tumour Response (Complete Response [CR], Partial Response [PR]) as Assessed by the Investigator According to the RECIST Version 1.1 | 50 Percentage of participants |
Secondary
Disease Control (CR, PR, Stable Disease [SD]) as Assessed by the Investigator According to RECIST 1.1
As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), =30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.
Time frame: Post baseline tumour-imaging was performed at every 8 weeks until Week 56 and then every 12 weeks; up to 802 days
Population: Treated Set (TS): The TS includes all patients who were documented to have taken at least 1 dose of afatinib.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Afatinib 40 mg | Disease Control (CR, PR, Stable Disease [SD]) as Assessed by the Investigator According to RECIST 1.1 | 83.3 Percentage of participants |
Secondary
Progression-free Survival (PFS) as Assessed by the Investigator According to RECIST 1.1.
Progression-free survival (PFS) is the time from treatment start to disease progression (or death if the patient died before progression). PFS as assessed based on investigator review according to the response evaluation criteria in solid tumours (RECIST) version 1.1.
Time frame: Post baseline tumour-imaging was performed at every 8 weeks until Week 56 and then every 12 weeks; up to 802 days
Population: Treated Set (TS): The TS includes all patients who were documented to have taken at least 1 dose of afatinib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Afatinib 40 mg | Progression-free Survival (PFS) as Assessed by the Investigator According to RECIST 1.1. | 10.94 Months |