Carcinoma, Non-Small-Cell Lung, ErbB Receptors
Conditions
Brief summary
Continuous treatment until progression or occurence of intolerable Adverse Event (AE) or end of trial. The end of trial is one year after the last patient has entered the study.
Interventions
DRUGAfatinib
afatinib starting at 30 mg daily dose
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologically or cytologically confirmed NSCLC Stage IV Cancer (includes cytologically proven pleural effusion or pericardial effusion) or recurrent disease. Staging is based on American Joint Committee on Cancer (AJCC) Staging for NSCLC 7th edition (R12-4710) * Evidence of common EGFR mutation (Del 19 and/or L858R) * Age \>= 70 years * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (R01-0787) * Further inclusion criteria apply.
Exclusion criteria
* Prior participation in an afatinib clinical study, even if not assigned to afatinib treatment * Prior systemic therapy for metastatic or recurrent NSCLC. * Concurrent investigational therapy or investigational therapy within 4 weeks of start of afatinib therapy * Radiotherapy within 4 weeks prior to start of study treatment, except as follows: * Palliative radiation to target organs other than chest may be allowed up to 2 weeks prior to study treatment, or * Single dose palliative treatment for symptomatic metastasis outside above allowance to be discussed with sponsor prior to enrolling. * Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study * Systemic chemotherapy, biological therapy, immunotherapy or investigational agents within 5 half-life of the drug or within four weeks prior to the start of afatinib treatment (if the half-life of the drug is unknown). * Men, capable of fathering a child, who are unwilling to use adequate contraception prior to study entry, for the duration of study participation, and for at least 28 days after treatment has ended. * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Reporting an Adverse Event (AE) Leading to Dose Reduction of Afatinib | On-treatment period + 28 days (residual effect period), up to 1057 + 28 days | On-treatment period = First administration of afatinib until progression or intolerable adverse events or other reasons necessitating withdrawal (participant's withdrawal of consent for study treatment, participant diagnosed with interstitial lung disease, participant no longer able to receive study treatments, participant had a significant deviation from the protocol or eligibility criteria). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Event = Diarrhoea of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or Higher | On-treatment period + 28 days (residual effect period), up to 1057 + 28 days | Percentage of participants with adverse event being diarrhoea of CTCAE grade 3 or higher. On-treatment period = First administration of afatinib until progression or intolerable adverse events or other reasons necessitating withdrawal (participant's withdrawal of consent for study treatment, participant diagnosed with interstitial lung disease, participant no longer able to receive study treatments, participant had a significant deviation from the protocol or eligibility criteria). |
| Percentage of Participants With Adverse Event = Rash/Acne (Grouped Term) of CTCAE Grade 3 or Higher | On-treatment period + 28 days (residual effect period), up to 1057 + 28 days | Percentage of participants with adverse event = rash/acne (grouped term) of CTCAE grade 3 or higher. MedDRA preferred terms that described AEs of similar nature were grouped together as grouped term to ensure that important events would not be underestimated. On-treatment period = First administration of afatinib until progression or intolerable adverse events or other reasons necessitating withdrawal (participant's withdrawal of consent for study treatment, participant diagnosed with interstitial lung disease, participant no longer able to receive study treatments, participant had a significant deviation from the protocol or eligibility criteria). |
| Percentage of Participants With Adverse Event = Stomatitis (Grouped Term) of CTCAE Grade 3 or Higher | On-treatment period + 28 days (residual effect period), up to 1057 + 28 days | Percentage of participants with adverse event = stomatitis (grouped term) of CTCAE grade 3 or higher. MedDRA preferred terms that described AEs of similar nature were grouped together as grouped term to ensure that important events would not be underestimated. On-treatment period = First administration of afatinib until progression or intolerable adverse events or other reasons necessitating withdrawal (participant's withdrawal of consent for study treatment, participant diagnosed with interstitial lung disease, participant no longer able to receive study treatments, participant had a significant deviation from the protocol or eligibility criteria). |
| Percentage of Participants With Adverse Event = Paronychia (Grouped Term) of CTCAE Grade 3 or Higher | On-treatment period + 28 days (residual effect period), up to 1057 + 28 days | Percentage of participants with adverse event = paronychia (grouped term) of CTCAE grade 3 or higher. MedDRA preferred terms that described AEs of similar nature were grouped together as grouped term to ensure that important events would not be underestimated. On-treatment period = First administration of afatinib until progression or intolerable adverse events or other reasons necessitating withdrawal (participant's withdrawal of consent for study treatment, participant diagnosed with interstitial lung disease, participant no longer able to receive study treatments, participant had a significant deviation from the protocol or eligibility criteria). |
| Time to First Dose Reduction of Afatinib Caused by Adverse Events | On-treatment period, up to 1057 days | Time to first dose reduction of afatinib caused by adverse events is defined as time from the date of the first administration of afatinib to the date of first dose reduction of afatinib caused by adverse events. Participants without AEs leading to dose reduction were censored at date of last intake of afatinib. On-treatment period = First administration of afatinib until progression or intolerable adverse events or other reasons necessitating withdrawal (participant's withdrawal of consent from study treatment, participant diagnosed with interstitial lung disease, participant no longer able to receive study treatments, participant had a significant deviation from the protocol or eligibility criteria). The cumulative probability of no dose reduction at the respective time point is given by the Kaplan-Meier estimate at the respective time point based on time to first dose reduction of afatinib caused by adverse events. |
Countries
United States
Participant flow
Recruitment details
Open-label, non-randomized, Phase IV, single arm study
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| Afatinib Giotrif® / Gilotrif® (Afatinib) starting at 30 mg daily dose
All participants received the same treatment (afatinib) with starting dose of 30 milligram (mg) per day with one possible dose reduction to 20 mg per day.
Mode of administration: Orally one film-coated tablet, once daily | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Patient refused to continue medication | 1 |
| Overall Study | Progressive disease | 11 |
| Overall Study | Study closed by sponsor | 9 |
| Overall Study | Treated off study with Afatinib. | 1 |
| Overall Study | Treatment change | 1 |
Baseline characteristics
| Characteristic | Afatinib |
|---|---|
| Age, Continuous | 79.2 years STANDARD_DEVIATION 5.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 8 Participants |
| Race (NIH/OMB) Black or African American | 2 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 | 14 Participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 7 / 25 |
| other Total, other adverse events | 25 / 25 |
| serious Total, serious adverse events | 10 / 25 |
Outcome results
Primary
Percentage of Participants Reporting an Adverse Event (AE) Leading to Dose Reduction of Afatinib
On-treatment period = First administration of afatinib until progression or intolerable adverse events or other reasons necessitating withdrawal (participant's withdrawal of consent for study treatment, participant diagnosed with interstitial lung disease, participant no longer able to receive study treatments, participant had a significant deviation from the protocol or eligibility criteria).
Time frame: On-treatment period + 28 days (residual effect period), up to 1057 + 28 days
Population: All participants who received at least one dose of afatinib were included in the treated set. The analyses of safety and efficacy were performed on the treated set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Afatinib | Percentage of Participants Reporting an Adverse Event (AE) Leading to Dose Reduction of Afatinib | 32.0 Percentage |
Secondary
Percentage of Participants With Adverse Event = Diarrhoea of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or Higher
Percentage of participants with adverse event being diarrhoea of CTCAE grade 3 or higher. On-treatment period = First administration of afatinib until progression or intolerable adverse events or other reasons necessitating withdrawal (participant's withdrawal of consent for study treatment, participant diagnosed with interstitial lung disease, participant no longer able to receive study treatments, participant had a significant deviation from the protocol or eligibility criteria).
Time frame: On-treatment period + 28 days (residual effect period), up to 1057 + 28 days
Population: All participants who received at least one dose of afatinib were included in the treated set. The analyses of safety and efficacy were performed on the treated set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Afatinib | Percentage of Participants With Adverse Event = Diarrhoea of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or Higher | 8.0 Percentage of participants |
Secondary
Percentage of Participants With Adverse Event = Paronychia (Grouped Term) of CTCAE Grade 3 or Higher
Percentage of participants with adverse event = paronychia (grouped term) of CTCAE grade 3 or higher. MedDRA preferred terms that described AEs of similar nature were grouped together as grouped term to ensure that important events would not be underestimated. On-treatment period = First administration of afatinib until progression or intolerable adverse events or other reasons necessitating withdrawal (participant's withdrawal of consent for study treatment, participant diagnosed with interstitial lung disease, participant no longer able to receive study treatments, participant had a significant deviation from the protocol or eligibility criteria).
Time frame: On-treatment period + 28 days (residual effect period), up to 1057 + 28 days
Population: All participants who received at least one dose of afatinib were included in the treated set. The analyses of safety and efficacy were performed on the treated set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Afatinib | Percentage of Participants With Adverse Event = Paronychia (Grouped Term) of CTCAE Grade 3 or Higher | 8.0 Percentage of participants |
Secondary
Percentage of Participants With Adverse Event = Rash/Acne (Grouped Term) of CTCAE Grade 3 or Higher
Percentage of participants with adverse event = rash/acne (grouped term) of CTCAE grade 3 or higher. MedDRA preferred terms that described AEs of similar nature were grouped together as grouped term to ensure that important events would not be underestimated. On-treatment period = First administration of afatinib until progression or intolerable adverse events or other reasons necessitating withdrawal (participant's withdrawal of consent for study treatment, participant diagnosed with interstitial lung disease, participant no longer able to receive study treatments, participant had a significant deviation from the protocol or eligibility criteria).
Time frame: On-treatment period + 28 days (residual effect period), up to 1057 + 28 days
Population: All participants who received at least one dose of afatinib were included in the treated set. The analyses of safety and efficacy were performed on the treated set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Afatinib | Percentage of Participants With Adverse Event = Rash/Acne (Grouped Term) of CTCAE Grade 3 or Higher | 0.0 Percentage of participants |
Secondary
Percentage of Participants With Adverse Event = Stomatitis (Grouped Term) of CTCAE Grade 3 or Higher
Percentage of participants with adverse event = stomatitis (grouped term) of CTCAE grade 3 or higher. MedDRA preferred terms that described AEs of similar nature were grouped together as grouped term to ensure that important events would not be underestimated. On-treatment period = First administration of afatinib until progression or intolerable adverse events or other reasons necessitating withdrawal (participant's withdrawal of consent for study treatment, participant diagnosed with interstitial lung disease, participant no longer able to receive study treatments, participant had a significant deviation from the protocol or eligibility criteria).
Time frame: On-treatment period + 28 days (residual effect period), up to 1057 + 28 days
Population: All participants who received at least one dose of afatinib were included in the treated set. The analyses of safety and efficacy were performed on the treated set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Afatinib | Percentage of Participants With Adverse Event = Stomatitis (Grouped Term) of CTCAE Grade 3 or Higher | 4.0 Percentage of participants |
Secondary
Time to First Dose Reduction of Afatinib Caused by Adverse Events
Time to first dose reduction of afatinib caused by adverse events is defined as time from the date of the first administration of afatinib to the date of first dose reduction of afatinib caused by adverse events. Participants without AEs leading to dose reduction were censored at date of last intake of afatinib. On-treatment period = First administration of afatinib until progression or intolerable adverse events or other reasons necessitating withdrawal (participant's withdrawal of consent from study treatment, participant diagnosed with interstitial lung disease, participant no longer able to receive study treatments, participant had a significant deviation from the protocol or eligibility criteria). The cumulative probability of no dose reduction at the respective time point is given by the Kaplan-Meier estimate at the respective time point based on time to first dose reduction of afatinib caused by adverse events.
Time frame: On-treatment period, up to 1057 days
Population: All participants who received at least one dose of afatinib were included in the treated set. The analyses of safety and efficacy were performed on the treated set.~The 'Number Analyzed' is the 'Number at risk' at the respective time point, that is the number of participants being treated with afatinib 30 mg at the respective time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Afatinib | Time to First Dose Reduction of Afatinib Caused by Adverse Events | 21 months | 0.6519 Probability |
| Afatinib | Time to First Dose Reduction of Afatinib Caused by Adverse Events | 0 months (= First administration of afatinib) | 1.0 Probability |
| Afatinib | Time to First Dose Reduction of Afatinib Caused by Adverse Events | 3 months | 0.7889 Probability |
| Afatinib | Time to First Dose Reduction of Afatinib Caused by Adverse Events | 6 months | 0.7450 Probability |
| Afatinib | Time to First Dose Reduction of Afatinib Caused by Adverse Events | 9 months | 0.6519 Probability |
| Afatinib | Time to First Dose Reduction of Afatinib Caused by Adverse Events | 12 months | 0.6519 Probability |
| Afatinib | Time to First Dose Reduction of Afatinib Caused by Adverse Events | 15 months | 0.6519 Probability |
| Afatinib | Time to First Dose Reduction of Afatinib Caused by Adverse Events | 18 months | 0.6519 Probability |
| Afatinib | Time to First Dose Reduction of Afatinib Caused by Adverse Events | 24 months | 0.6519 Probability |
| Afatinib | Time to First Dose Reduction of Afatinib Caused by Adverse Events | 27 months | 0.6519 Probability |
| Afatinib | Time to First Dose Reduction of Afatinib Caused by Adverse Events | 30 months | 0.6519 Probability |
| Afatinib | Time to First Dose Reduction of Afatinib Caused by Adverse Events | 33 months | 0.6519 Probability |