Non-Squamous Non-Small Cell Lung Cancer
Conditions
Brief summary
This open-label, single arm study will assess the correlation between Tarceva (erlotinib)-induced rash and efficacy in participants with inoperable, locally advanced, recurrent or metastatic non-small cell lung cancer (NSCLC) receiving first-line therapy for advanced disease. Participants will receive Tarceva at a dose of 150 mg daily orally, with dose adjustments according to protocol depending on toxicity. Anticipated time on study treatment is until disease progression, unacceptable toxicity, or withdrawal due to any reason.
Interventions
DRUGerlotinib [Tarceva]
150 mg orally daily, with dose-reductions to 100 mg or 50 mg orally daily according to protocol
Sponsors
Clalit Health Services
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 participants, \>/= 18 years of age * Inoperable, locally advanced, recurrent or metastatic (Stage IIIB or IV) non-small cell lung cancer (NSCLC) * Presence of epidermal growth factor receptor (EGFR) mutations * Previously untreated with any systemic anti-neoplastic therapy for advanced disease * Last dose of a prior systemic anti-neoplastic therapy for early-stage disease \>/= 4 weeks before study start, and patient recovered from acute toxicities of any previous therapy * A life expectancy of at least 12 weeks * Able to comply with the study and its follow-up procedures * Female participants had to be postmenopausal (24 months of amenorrhea), surgically sterile or agree to use a physical method of contraception. Male participants had to be surgically sterile or agree to use a barrier method of contraception. Women with an intact uterus (unless amenorrhoeic for the last 24 months) had to have a negative pregnancy test (urine or serum) within 3 days prior to erlotinib treatment initiation in the study. Male and female participants had to use effective contraception during the study and for a period of 90 days following the last administration of erlotinib. Acceptable methods of contraception included an established hormonal therapy or intrauterine device for females, and the use of a barrier contraceptive (i.e. diaphragm or condoms)
Exclusion criteria
* Pregnant or breast feeding women * Granulocyte count \<1.5 x 109/L and platelet count \<100\*10\^9/L * Serum bilirubin \>1.5 upper limit of normal (ULN) * Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 2 \* ULN (or \>5 \* ULN if clearly attributable to liver metastasis) * Serum creatinine \>1.5 ULN or creatinine clearance \<60 mL/min * Known allergy or other adverse reaction to study drug or any other related compound * Any significant unstable systemic disease (including active infection, grade 4 hypertension, unstable angina, congestive heart failure, hepatic, renal or metabolic disease) * Prior systemic anti-neoplastic therapy with HER1/EGFR inhibitors (as small molecule or monoclonal antibody therapy) * Newly diagnosed or not yet definitively treated (i.e. stable disease \>/= 2 months) CNS metastases or spinal cord compression * Any significant ophthalmological abnormality, especially those likely to increase the risk of corneal epithelial lesions (the use of contact lenses is not recommended during the study) * Participants who could not take oral medication, who required intravenous alimentation, had had prior surgical procedures affecting absorption, or had active peptic ulcer disease * Active cancer other than NSCLC, except for basal cell or squamous cell carcinomas of the skin that have been excised and cured
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) According to Grade of Rash | Day 1 of treatment period until disease progression or death (approximately up to 67 months) | PFS was defined as the time from start of treatment to the date of the first documented progression according to revised Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 or the date of death for any reason in the absence of progressive disease (PD). Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Erlotinib Dose Reductions Due to Rash Grade 3-4 | Day 1 of treatment period until disease progression or death (approximately up to 67 months) | — |
| Progression-Free Survival (PFS) in Participants With Erlotinib Dose Reductions Due to Rash Grade 3-4 | Day 1 of treatment period until disease progression or death (approximately up to 67 months) | PFS was defined as the time from start of treatment to the date of the first documented progression according to revised Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 or the date of death for any reason in the absence of progressive disease (PD). Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. |
Countries
Israel
Participant flow
Pre-assignment details
A total of 60 participants were enrolled in the study from 12 centers across Israel.
Participants by arm
| Arm | Count |
|---|---|
| Erlotinib Participants received 150 milligrams (mg) of Erlotinib orally daily, from Day 1 of the treatment period until unacceptable toxicity, disease progression or withdrawal due to any reason. | 60 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 5 |
| Overall Study | Investigator's Discretion | 5 |
| Overall Study | Participant Withdrew Consent | 3 |
| Overall Study | Progressive Disease | 45 |
| Overall Study | Rash Adverse Event | 1 |
| Overall Study | Sponsor's decision | 1 |
Baseline characteristics
| Characteristic | Erlotinib |
|---|---|
| Age, Continuous | 69.0 years STANDARD_DEVIATION 12.3 |
| Sex: Female, Male Female | 41 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 59 |
| other Total, other adverse events | 59 / 59 |
| serious Total, serious adverse events | 19 / 59 |
Outcome results
Primary
Progression-free Survival (PFS) According to Grade of Rash
PFS was defined as the time from start of treatment to the date of the first documented progression according to revised Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 or the date of death for any reason in the absence of progressive disease (PD). Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.
Time frame: Day 1 of treatment period until disease progression or death (approximately up to 67 months)
Population: Efficacy set included all participants who received at least one dose of study drug. Here, Number Analyzed represents the number of participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Erlotinib | Progression-free Survival (PFS) According to Grade of Rash | Grade 0 | 2.16 months |
| Erlotinib | Progression-free Survival (PFS) According to Grade of Rash | Grade 1 | 6.62 months |
| Erlotinib | Progression-free Survival (PFS) According to Grade of Rash | Grade 2 | 10.00 months |
| Erlotinib | Progression-free Survival (PFS) According to Grade of Rash | Grade 3 | 15.28 months |
p-value: 0.00595% CI: [0.41, 0.83]Log Rank
Secondary
Percentage of Participants With Erlotinib Dose Reductions Due to Rash Grade 3-4
Time frame: Day 1 of treatment period until disease progression or death (approximately up to 67 months)
Population: Efficacy set included all participants who received at least one dose of study drug. Here, Number Analyzed represents the number of participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib | Percentage of Participants With Erlotinib Dose Reductions Due to Rash Grade 3-4 | Rash Grade III | 8.5 percentage of participants |
Secondary
Progression-Free Survival (PFS) in Participants With Erlotinib Dose Reductions Due to Rash Grade 3-4
PFS was defined as the time from start of treatment to the date of the first documented progression according to revised Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 or the date of death for any reason in the absence of progressive disease (PD). Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.
Time frame: Day 1 of treatment period until disease progression or death (approximately up to 67 months)
Population: Efficacy set included all participants who received at least one dose of study drug. Here, Number Analyzed represents the number of participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Erlotinib | Progression-Free Survival (PFS) in Participants With Erlotinib Dose Reductions Due to Rash Grade 3-4 | Rash grade III | 13.72 months |