Non-Squamous Non-Small Cell Lung Cancer
Conditions
Brief summary
This single arm, open-label study will evaluate the efficacy and safety of erlotinib (Tarceva) in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations.
Interventions
DRUGErlotinib
Erlotinib 150 mg tablet will be given orally 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
* Locally advanced or metastatic NSCLC with EGFR mutations * Measurable disease according to RECIST criteria * Adequate hematological, renal and liver function
Exclusion criteria
* Previous chemotherapy or therapy against EGFR for metastatic disease * Symptomatic cerebral metastases * Pre-existing disease of the lung parenchyma such as lung fibrosis, lymphangitic carcinomatosis * History of another malignancy except for carcinoma in-situ of the cervix, adequately treated basal cell skin carcinoma, or radically treated prostate carcinoma with good prognosis * Concomitant use of coumarins
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response (Complete Response [CR]/Partial Response [PR]) Based on Computer Tomography (CT) or Magnetic Resonance Imaging (MRI) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 | Baseline up to 5 years (assessed at Baseline, every 8 weeks until disease progression or death or end of treatment period [up to 5 years]) | Objective response (OR) was based on criteria related to changes in size of target lesions according to modified RECIST. Target lesions were selected on the basis of their size (lesions with the longest diameter) as well as the feasibility of reproducible repeated measurements. OR was the sum of complete response (CR) and partial response (PR) four at least 4 weeks during treatment. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) Based on CT or MRI According to RECIST v 1.1 | Baseline up to 5 years (assessed at Baseline, every 8 weeks until disease progression or death or end of treatment period [up to 5 years]) | Kaplan Meier estimate of the median PFS was defined as the time at which half of the participants have progressed (progressive disease \[PD\]) based on RECIST tumor response criteria or died from any cause, whichever occurred first. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Patients who had not died or progressed at the time of the final analysis were censored at the date of last contact. |
| Overall Survival | Baseline up to 5 years | Overall Survival (OS) was defined as the time between the date of randomization and the date of death due to any cause. |
| Percentage of Participants With Adverse Events | Baseline up to 5 years | An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. |
| Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Mutation in Study Population | Screening (21 days prior to Day 1) | Mutations in the EGFR included exon 19 deletion mutations and the single-point substitution mutation L858R in exon 21. |
| Median Time Taken From the First Response Until Disease Progression Based on RECIST v 1.1 as Determined by the Investigator | Baseline up to 5 years (assessed at Baseline, every 8 weeks until disease progression or death or end of treatment period [up to 5 years]) | The response duration was defined as the time of initial response (complete response (CR) /partial response (PR) whichever is first recorded) until documented disease progression. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Disease progression was defined as At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). |
Countries
Portugal
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Erlotinib Participants received erlotinib 150 millgrams (mg) orally daily until disease progression. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Decision of Investigator | 1 |
Baseline characteristics
| Characteristic | Erlotinib |
|---|---|
| Age, Continuous | 66.33 years STANDARD_DEVIATION 9.21 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 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 | 30 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 30 |
| other Total, other adverse events | 29 / 30 |
| serious Total, serious adverse events | 8 / 30 |
Outcome results
Primary
Percentage of Participants With Objective Response (Complete Response [CR]/Partial Response [PR]) Based on Computer Tomography (CT) or Magnetic Resonance Imaging (MRI) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
Objective response (OR) was based on criteria related to changes in size of target lesions according to modified RECIST. Target lesions were selected on the basis of their size (lesions with the longest diameter) as well as the feasibility of reproducible repeated measurements. OR was the sum of complete response (CR) and partial response (PR) four at least 4 weeks during treatment. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time frame: Baseline up to 5 years (assessed at Baseline, every 8 weeks until disease progression or death or end of treatment period [up to 5 years])
Population: The ITT population was defined as all subjects who are enrolled to the treatment phase of the study, regardless if they completed treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib | Percentage of Participants With Objective Response (Complete Response [CR]/Partial Response [PR]) Based on Computer Tomography (CT) or Magnetic Resonance Imaging (MRI) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 | 63.3 percentage of participants |
Secondary
Median Time Taken From the First Response Until Disease Progression Based on RECIST v 1.1 as Determined by the Investigator
The response duration was defined as the time of initial response (complete response (CR) /partial response (PR) whichever is first recorded) until documented disease progression. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Disease progression was defined as At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
Time frame: Baseline up to 5 years (assessed at Baseline, every 8 weeks until disease progression or death or end of treatment period [up to 5 years])
Population: The ITT population was defined as all subjects who are enrolled to the treatment phase of the study, regardless if they completed treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib | Median Time Taken From the First Response Until Disease Progression Based on RECIST v 1.1 as Determined by the Investigator | 41.5 weeks |
Secondary
Overall Survival
Overall Survival (OS) was defined as the time between the date of randomization and the date of death due to any cause.
Time frame: Baseline up to 5 years
Population: The ITT population was defined as all subjects who are enrolled to the treatment phase of the study, regardless if they completed treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib | Overall Survival | 83 weeks |
Secondary
Percentage of Participants With Adverse Events
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time frame: Baseline up to 5 years
Population: The safety population was identical to the ITT population, which included all participants enrolled in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib | Percentage of Participants With Adverse Events | 29 percentage of participants |
Secondary
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Mutation in Study Population
Mutations in the EGFR included exon 19 deletion mutations and the single-point substitution mutation L858R in exon 21.
Time frame: Screening (21 days prior to Day 1)
Population: The ITT population was defined as all subjects who are enrolled to the treatment phase of the study, regardless if they completed treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib | Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Mutation in Study Population | Exon 19 mutation | 40 percentage of participants |
| Erlotinib | Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Mutation in Study Population | Exon 21 mutation | 60 percentage of participants |
Secondary
Progression Free Survival (PFS) Based on CT or MRI According to RECIST v 1.1
Kaplan Meier estimate of the median PFS was defined as the time at which half of the participants have progressed (progressive disease \[PD\]) based on RECIST tumor response criteria or died from any cause, whichever occurred first. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Patients who had not died or progressed at the time of the final analysis were censored at the date of last contact.
Time frame: Baseline up to 5 years (assessed at Baseline, every 8 weeks until disease progression or death or end of treatment period [up to 5 years])
Population: The ITT population was defined as all subjects who are enrolled to the treatment phase of the study, regardless if they completed treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib | Progression Free Survival (PFS) Based on CT or MRI According to RECIST v 1.1 | 40 weeks |