Carcinoma, Non-Small-Cell Lung
Conditions
Brief summary
To evaluate the safety and tolerability of afatinib (Giotrif) in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR mutation(s) and have never been treated with an EGFR-TKI
Interventions
DRUGAfatinib
Patients received a daily dose of 40 milligrams (mg) of afatinib (Giotrif®), in the form of film-coated tablet over a 28 day cycle. Afatinib was taken orally with 250 milliliters (mL) of water at the same time of the day and without eating anything for at least 3 hours. Patients continued on treatment for as long as there was no disease progression or no other trial withdrawal criteria. The dose was reduced to 30 mg or 20 mg once daily when the initial dose was not tolerated by the patient.
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
Patients with: * locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) * Epidermal Growth Factor Receptor (EGFR) mutation-positive result per the institution's testing methodology. * Adequate organ function, defined as all of the following: 1. Absolute Neutrophil Count (ANC) \> 1500/mm3. (ANC \>1000/mm3 may be considered in special circumstances such as benign cyclical neutropenia as judged by the investigator and in discussion with the sponsor). 2. Platelet count \>75,000/mm3 3. Serum creatinine \< 1.5 times of the upper limit of normal 4. Total Bilirubin \< 1.5 times upper limit of (institutional) normal (Patients with Gilbert's syndrome total bilirubin must be \<4 times institutional upper limit of normal). 5. Aspartate Amino Transferase (AST) or Alanine Amino Transferase (ALT) \< three times the upper limit of (institutional) normal (ULN) (if related to liver metastases \< five times ULN). * Eastern Cooperative Oncology Group (ECOG) score between 0 - 2 * written informed consent by patient or guardian prior to admission into the trial that is consistent with International Conference on Harmonisation (ICH)- Good Clinical Practice (GCP) guidelines and local law.
Exclusion criteria
Patients who or with: * prior treatment with an EGFR tyrosine kinase inhibitor (TKI) * anti-cancer treatment within 2 weeks prior to start of trial treatment (continued use of anti-androgens and/or gonadorelin analogues for treatment of prostate cancer permitted) * radiotherapy within 14 days prior to drug administration, except as follows: 1. Palliative radiation to organs other than chest may be allowed up to 2 weeks prior to drug administration, and 2. Single dose palliative treatment for symptomatic metastasis outside above allowance to be discussed with sponsor prior to enrolling. * previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ or effectively treated malignancy that has been in remission for more than 3 years and is considered to be cured. * known pre-existing interstitial lung disease * meningeal carcinomatosis and symptomatic brain metastases (patients with asymptomatic brain metastases, who were previously treated, are eligible provided they have had Stable Disease (SD) for at least 4 weeks on stable doses of medication)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 | From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. | Number of patients with any treatment emergent adverse event (AE) according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. |
Countries
Australia, Austria, Czechia, Greece, Hungary, Israel, Italy, Poland, Portugal, Russia, Spain
Participant flow
Recruitment details
Open-label, multicentre, single-arm trial to evaluate the safety, tolerability and efficacy of afatinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation(s) who had never been treated with an EGFR tyrosine kinase inhibitor (TKI).
Pre-assignment details
All participants were screened for eligibility prior to participation in the trial. Participants attended a specialist site which ensured that they (the participants) strictly met all inclusion and none of the exclusion criteria. Participants were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| Afatinib Treated-patients Patients diagnosed with EGFR mutation positive non-small cell lung cancer (NSCLC) locally advanced or metastatic who have never been treated with EGFR tyrosine kinase inhibitors (TKI) received a daily dose of 40 milligrams (mg) of afatinib (Giotrif®), in the form of film-coated tablet over a 28 day cycle. Afatinib was taken orally with 250 milliliters (mL) of water at the same time of the day and without eating anything for at least 3 hours. Patients continued on treatment for as long as there was no disease progression or no other trial withdrawal criteria. The dose was reduced to 30 mg or 20 mg once daily when the initial dose was not tolerated by the patient. | 479 |
| Total | 479 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Non-compliant with protocol | 4 |
| Overall Study | Not treated - not signed privacy informed consent | 2 |
| Overall Study | Other adverse events (AE) | 62 |
| Overall Study | Other than listed | 13 |
| Overall Study | Patient refused to continue medication | 21 |
| Overall Study | Patients who switched to commercial drug | 11 |
| Overall Study | Progressive disease | 342 |
| Overall Study | Worsening or AE of underlying cancer disease | 24 |
Baseline characteristics
| Characteristic | Afatinib Treated-patients |
|---|---|
| Age, Continuous | 64.2 Years STANDARD_DEVIATION 10.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 10 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 465 Participants |
| Sex: Female, Male Female | 314 Participants |
| Sex: Female, Male Male | 165 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 127 / 479 |
| other Total, other adverse events | 268 / 479 |
| serious Total, serious adverse events | 210 / 479 |
Outcome results
Primary
Number of Patients With Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
Number of patients with any treatment emergent adverse event (AE) according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Time frame: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days.
Population: Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Afatinib Treated-patients | Number of Patients With Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 | 478 Participants |