Carcinoma，Non-Small-Cell Lung
Conditions
Brief summary
This open-label, single-arm, multi-center study will evaluate the progression-free survival in participants with histologically documented, advanced and/or metastatic chemotherapy naive, non-small cell lung cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) positive mutations and receiving erlotinib treatment. The anticipated time on study treatment is until disease progression, unacceptable toxicity, withdrawal due to any reason or death.
Interventions
DRUGErlotinib
Erlotinib 150 mg oral doses will be administered daily.
Sponsors
Hoffmann-La Roche
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
* Histological documented adenocarcinoma, locally advanced - Stage IIIB, metastatic - Stage IV or recurrent non-squamous NSCLC * Activated EGFR mutation positive status (Exons 19 and 21) for treatment phase * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Life expectancy greater than or equal to (≥) 12 weeks * Evidence of disease with at least one measurable disease evaluation on Response Evaluation Criteria in Solid Tumors (RECIST) * Adequate hematological , liver and renal function
Exclusion criteria
* Known hypersensitivity to erlotinib or any of its excipients * Squamous non-small cell or small cell tumors or absence of histological report * Neoadjuvant/adjuvant chemotherapy within 6 months prior to enrollment * Prior exposure to inhibitors of EGFR * Prior chemotherapy or treatment with another systemic anti-cancer agent for the treatment of the participant's current stage of disease * Any significant ophthalmologic abnormality, especially severe dry eye syndrome, keratoconjunctivitis sicca, Sjögren syndrome, severe exposure keratitis or any other disorder likely to increase the risk of corneal epithelial lesions * Radical radiotherapy with curative intent within 28 days prior to enrollment * Any active non-controlled systemic disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS), as Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | Baseline up to approximately 4 years | PFS was the time from inclusion in the study to the date of first documented PD or death from any cause, whichever occurred first. Participants without event were censored at the date of the last tumor assessment where non-progression was documented. If a participant received a second anti-cancer therapy without prior documentation of disease progression, the participant was censored at the date of last tumor assessment before starting new chemotherapy. Analysis was performed using Kaplan-Meier method. PD was defined as at least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete Response (CR) And Partial Response (PR) as Assessed by the Investigator Using RECIST v1.1 | Baseline up to approximately 4 years | CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter compared to baseline. |
| Percentage of Participants Who Were Alive One Year After Study Treatment Initiation | Year 1 | — |
| Percentage of Participants by Localization of PD, as Assessed by Investigator Using RECIST v1.1 | Baseline up to approximately 4 years | PD was assessed using RECIST v1.1. PD was defined as at least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. Percentage of participants by localization of PD were reported. Localization included: Left lung inferior lobe; Para-aortic; Left lung upper lobe; Right lung inferior lobe; and Infracranial. |
| Time to Disease Progression, as Assessed by Investigator Using RECIST v1.1 | Baseline up to approximately 4 years | Time to disease progression was defined as the time from baseline evaluation to the first date PD was recorded. Participants without progression were censored at the date of last tumor assessment where non-progression was documented. PD was defined as at least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. |
| Number of EGFR Positive Participants Classified Based on Type of EGFR Mutations | Day 1 | Participants with NSCLC have tumor associated with EGFR mutations. These mutations occur within EGFR Exons 18-21, which encodes a portion of the EGFR kinase domain. |
| Percentage of Similar EGFR Mutations Between Matched Plasma and Tumor Tissue Samples | Baseline up to approximately 4 years | — |
| Number of EGFR Positive Participants Classified Based on Smoking Status | Day 1 | Participants were asked: Have you smoked at least 100 cigarettes in your entire life? and Do you now smoke cigarettes every day, some days, or not at all? Responses were grouped into three categories: Current Smoker, Former Smoker, and Non-Smoker. Participants who reported smoking at least 100 cigarettes in their lifetime and who, at the time of survey, smoked either every day or some days were defined as 'Current smoker'. Participants who reported smoking at least 100 cigarettes in their lifetime and who, at the time of the survey, did not smoke at all were defined as 'Former smoker'. Participants who reported never having smoked 100 cigarettes were defined as 'Non-smoker'. |
Countries
Romania
Participant flow
Pre-assignment details
Ninety participants were screened and 23 participants were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Erlotinib Participants received 150 mg erlotinib orally daily until disease progression, unacceptable toxicity, withdrawal due to any reason or death. | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Erlotinib |
|---|---|
| Age, Continuous | 55.52 Years STANDARD_DEVIATION 11.59 |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 23 |
| serious Total, serious adverse events | 5 / 23 |
Outcome results
Primary
Progression-Free Survival (PFS), as Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
PFS was the time from inclusion in the study to the date of first documented PD or death from any cause, whichever occurred first. Participants without event were censored at the date of the last tumor assessment where non-progression was documented. If a participant received a second anti-cancer therapy without prior documentation of disease progression, the participant was censored at the date of last tumor assessment before starting new chemotherapy. Analysis was performed using Kaplan-Meier method. PD was defined as at least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.
Time frame: Baseline up to approximately 4 years
Population: All enrolled participants.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Erlotinib | Progression-Free Survival (PFS), as Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 387.000 days | 95% Confidence Interval 85.32 |
Secondary
Number of EGFR Positive Participants Classified Based on Smoking Status
Participants were asked: Have you smoked at least 100 cigarettes in your entire life? and Do you now smoke cigarettes every day, some days, or not at all? Responses were grouped into three categories: Current Smoker, Former Smoker, and Non-Smoker. Participants who reported smoking at least 100 cigarettes in their lifetime and who, at the time of survey, smoked either every day or some days were defined as 'Current smoker'. Participants who reported smoking at least 100 cigarettes in their lifetime and who, at the time of the survey, did not smoke at all were defined as 'Former smoker'. Participants who reported never having smoked 100 cigarettes were defined as 'Non-smoker'.
Time frame: Day 1
Population: All enrolled participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib | Number of EGFR Positive Participants Classified Based on Smoking Status | Non-smoker | 17 participants |
| Erlotinib | Number of EGFR Positive Participants Classified Based on Smoking Status | Former smoker | 3 participants |
| Erlotinib | Number of EGFR Positive Participants Classified Based on Smoking Status | Current smoker | 3 participants |
Secondary
Number of EGFR Positive Participants Classified Based on Type of EGFR Mutations
Participants with NSCLC have tumor associated with EGFR mutations. These mutations occur within EGFR Exons 18-21, which encodes a portion of the EGFR kinase domain.
Time frame: Day 1
Population: All enrolled participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib | Number of EGFR Positive Participants Classified Based on Type of EGFR Mutations | Exon 19 deletions | 20 participants |
| Erlotinib | Number of EGFR Positive Participants Classified Based on Type of EGFR Mutations | Exon 21 L858R mutations | 3 participants |
Secondary
Percentage of Participants by Localization of PD, as Assessed by Investigator Using RECIST v1.1
PD was assessed using RECIST v1.1. PD was defined as at least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. Percentage of participants by localization of PD were reported. Localization included: Left lung inferior lobe; Para-aortic; Left lung upper lobe; Right lung inferior lobe; and Infracranial.
Time frame: Baseline up to approximately 4 years
Population: All enrolled participants with available data for this outcome.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib | Percentage of Participants by Localization of PD, as Assessed by Investigator Using RECIST v1.1 | Left lung inferior lobe | 24 percentage of participants |
| Erlotinib | Percentage of Participants by Localization of PD, as Assessed by Investigator Using RECIST v1.1 | Para-aortic | 14 percentage of participants |
| Erlotinib | Percentage of Participants by Localization of PD, as Assessed by Investigator Using RECIST v1.1 | Left lung upper lobe | 10 percentage of participants |
| Erlotinib | Percentage of Participants by Localization of PD, as Assessed by Investigator Using RECIST v1.1 | Right lung inferior lobe | 14 percentage of participants |
| Erlotinib | Percentage of Participants by Localization of PD, as Assessed by Investigator Using RECIST v1.1 | Infracranial | 38 percentage of participants |
Secondary
Percentage of Participants Who Were Alive One Year After Study Treatment Initiation
Time frame: Year 1
Population: All enrolled participants with available data for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib | Percentage of Participants Who Were Alive One Year After Study Treatment Initiation | 85.7 percentage of participants |
Secondary
Percentage of Participants With Complete Response (CR) And Partial Response (PR) as Assessed by the Investigator Using RECIST v1.1
CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter compared to baseline.
Time frame: Baseline up to approximately 4 years
Population: All enrolled participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib | Percentage of Participants With Complete Response (CR) And Partial Response (PR) as Assessed by the Investigator Using RECIST v1.1 | CR | 0 percentage of participants |
| Erlotinib | Percentage of Participants With Complete Response (CR) And Partial Response (PR) as Assessed by the Investigator Using RECIST v1.1 | PR | 8.7 percentage of participants |
Secondary
Percentage of Similar EGFR Mutations Between Matched Plasma and Tumor Tissue Samples
Time frame: Baseline up to approximately 4 years
Population: No participants were analyzed for this outcome as no plasma samples were collected during the study.
Secondary
Time to Disease Progression, as Assessed by Investigator Using RECIST v1.1
Time to disease progression was defined as the time from baseline evaluation to the first date PD was recorded. Participants without progression were censored at the date of last tumor assessment where non-progression was documented. PD was defined as at least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.
Time frame: Baseline up to approximately 4 years
Population: All enrolled participants.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Erlotinib | Time to Disease Progression, as Assessed by Investigator Using RECIST v1.1 | 193.00 days | 95% Confidence Interval 70.323 |