Non-Squamous Non-Small Cell Lung Cancer
Conditions
Brief summary
This open-label study will assess the efficacy and safety of Tarceva (Erlotinib) in patients with locally advanced, metastatic or recurrent non-small cell lung cancer who have not received previous chemotherapy for their disease and who present epidermal growth factor receptor mutations. Patients will receive Tarceva 150 mg orally daily until disease progression or unacceptable toxicity occurs.
Interventions
DRUGerlotinib [Tarceva]
150 mg 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
* Adult patients, \>/= 18 years of age * Locally advanced (Stage IIIB), metastatic (Stage IV) or recurrent non-small cell lung cancer with mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) * At least one measurable lesion according to RECIST criteria * European Cooperative Oncology Group (ECOG) performance status 0-2 * Adequate hematological, liver and renal function * Patients with stable cerebral metastases who have received surgical or radiotherapy will be eligible
Exclusion criteria
* Previous chemotherapy or therapy against EGFR for metastatic disease (neoadjuvant or adjuvant therapy after radical surgery is allowed if finalized \>/= 6 months before entering the study) * History of another neoplasm except for carcinoma in situ of the cervix, adequately treated basal cell skin carcinoma, radically treated prostate carcinoma with good prognosis (Gleason \</= 6), or another curatively treated neoplasm without evidence of disease in the last 5 years * Symptomatic cerebral metastases * Any significant ophthalmologic abnormality * Use of coumarins * Pregnant or breast-feeding women * Pre-existing parenchymal lung disease such as pulmonary fibrosis, lymphangiosis and carcinomatosis (if this is the only presence of the disease)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (Tumour Assessments According to RECIST Criteria) | Until participants had disease progression, unacceptable toxicity or died; approximately 24 months. | Progression free survival is (PFS) defined as the time from the first dose of Erlotinib to the date of first occurrence of disease progression or death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (Investigator Assessed) | Visit 4, Visit 6, Visit 10 and Visit 22; (up to approximately 24 months) | Objective response rate (ORR) was defined by RECIST criteria: Partial response (PR) was defined as ≥ 30% decrease in the sum of longest diameter of all target lesions, from the baseline sum. Complete response (CR) was defined as disappearance of all target and non-target lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments within 4 weeks. Progression of disease (PD) = 20% increase in the sum of longest diameter of all target lesions, from smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions. Stable Disease (SD) = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on the study. |
| Safety: Incidence of Adverse Events | Until participants had disease progression, unacceptable toxicity, or died; approximately 24 months. | An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. An SAE is any experience that suggests a significant hazard, contraindication, side effect, or precaution. |
| Overall Survival | Until participants had disease progression, unacceptable toxicity, or died; approximately 24 months. | The overall survival (OS) is defined as the time from the first dose of Erlotinib to the date of death due to any cause. |
Countries
Bulgaria
Participant flow
Pre-assignment details
In all 145 participants were screened, of these 6 participants were randomized; major reason for screen failure was negative mutation status.
Participants by arm
| Arm | Count |
|---|---|
| Erlotinib Participants received recommended dose of Erlotinib (150 mg/day). No dose escalation of erlotinib was permitted. Participants were treated until disease progression, unacceptable toxicity, death or participant request for discontinuation. | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Progression of disease | 3 |
Baseline characteristics
| Characteristic | Erlotinib |
|---|---|
| Age, Continuous | 66.5 years STANDARD_DEVIATION 6.19 |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 6 |
| serious Total, serious adverse events | 1 / 6 |
Outcome results
Primary
Progression-free Survival (Tumour Assessments According to RECIST Criteria)
Progression free survival is (PFS) defined as the time from the first dose of Erlotinib to the date of first occurrence of disease progression or death.
Time frame: Until participants had disease progression, unacceptable toxicity or died; approximately 24 months.
Population: The Intent-to-treat (ITT population) included all patients with at least one valid post-baseline assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib | Progression-free Survival (Tumour Assessments According to RECIST Criteria) | 223 Days |
Secondary
Objective Response Rate (Investigator Assessed)
Objective response rate (ORR) was defined by RECIST criteria: Partial response (PR) was defined as ≥ 30% decrease in the sum of longest diameter of all target lesions, from the baseline sum. Complete response (CR) was defined as disappearance of all target and non-target lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments within 4 weeks. Progression of disease (PD) = 20% increase in the sum of longest diameter of all target lesions, from smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions. Stable Disease (SD) = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on the study.
Time frame: Visit 4, Visit 6, Visit 10 and Visit 22; (up to approximately 24 months)
Population: The ITT population included all patients with at least one valid post-baseline assessment. Only those participants available at the specified time points were analyzed (represented by n=X).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib | Objective Response Rate (Investigator Assessed) | Visit 6, PR, n=2 | 33.3 Percentage |
| Erlotinib | Objective Response Rate (Investigator Assessed) | Visit 6, SD, n=2 | 33.3 Percentage |
| Erlotinib | Objective Response Rate (Investigator Assessed) | Visit 4, SD, n=5 | 83.3 Percentage |
| Erlotinib | Objective Response Rate (Investigator Assessed) | Visit 4, PR, n=1 | 16.7 Percentage |
| Erlotinib | Objective Response Rate (Investigator Assessed) | Visit 6, PD, n=2 | 33.3 Percentage |
| Erlotinib | Objective Response Rate (Investigator Assessed) | Visit 10, PR, n=2 | 33.3 Percentage |
| Erlotinib | Objective Response Rate (Investigator Assessed) | Visit 10, PD, n=4 | 66.7 Percentage |
| Erlotinib | Objective Response Rate (Investigator Assessed) | Visit 22, PD, n=6 | 100 Percentage |
Comparison: Response assessment of Stable Disease Vs Partial Response at Visit 4 (Two proportions for Stable Disease Vs Partial Response of Erlotinib): The observed significance value of performed test for differences between two proportions for Stable Disease Vs Partial Response was analyzed.p-value: 0.045Clopper-Pearson exact method
Comparison: Response assessment of Stable Disease Vs Partial Response at Visit 6 (Two proportions for Stable Disease Vs Partial Response of Erlotinib): The observed significance value of performed test for differences between two proportions for Stable Disease Vs Partial Response was analyzedp-value: 1Clopper-Pearson exact method
Comparison: Response assessment of Partial Response Vs Progression of disease at Visit 6 (Two proportions for of Partial Response Vs Progression of disease of Erlotinib): The observed significance value of performed test for differences between two proportions for of Partial Response Vs Progression of disease was analyzedp-value: 1Clopper-Pearson exact method
Comparison: Response assessment of Stable Disease Vs Progression of disease at Visit 6 (Two proportions for of Stable Disease Vs Progression of disease of Erlotinib): The observed significance value of performed test for differences between two proportions for of Stable Disease Vs Progression of disease was analyzedp-value: 1Clopper-Pearson exact method
Comparison: Response assessment of Partial Response Vs Progression of disease at Visit 10 (Two proportions for of Partial Response Vs Progression of disease of Erlotinib): The observed significance value of performed test for differences between two proportions for of Partial Response Vs Progression of disease was analyzedp-value: 0.274Clopper-Pearson exact method
Secondary
Overall Survival
The overall survival (OS) is defined as the time from the first dose of Erlotinib to the date of death due to any cause.
Time frame: Until participants had disease progression, unacceptable toxicity, or died; approximately 24 months.
Population: The ITT population included all patients with at least one valid post-baseline assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib | Overall Survival | 401 Days |
Secondary
Safety: Incidence of Adverse Events
An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. An SAE is any experience that suggests a significant hazard, contraindication, side effect, or precaution.
Time frame: Until participants had disease progression, unacceptable toxicity, or died; approximately 24 months.
Population: All participants who received at least one dose of study medication and had a safety assessment performed post baseline were included in the safety population. Participants were analyzed according to the first dose received during the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib | Safety: Incidence of Adverse Events | Any AE | 6 participants |
| Erlotinib | Safety: Incidence of Adverse Events | SAE | 1 participants |