Non-Squamous Non-Small Cell Lung Cancer
Conditions
Brief summary
This randomized parallel group study will assess the efficacy and safety of erlotinib \[Tarceva\], as monotherapy or intermittent dosing with docetaxel, in second-line setting in former-smoker male patients with advanced or metastatic squamous non-small cell lung cancer. Patients will be randomized to receive either Tarceva (150 mg/day orally) as monotherapy or 4 cycles of docetaxel (75 mg/m2 intravenously every 3 weeks) plus Tarceva (150 mg/day orally, days 2-16 each cycle) followed by Tarceva monotherapy. Anticipated time on study treatment is until disease progression.
Interventions
DRUGdocetaxel
75 mg/m2 intravenously every 3 weeks for 4 cycles
DRUGerlotinib [Tarceva]
150 mg/day orally, days 2-16 each 3-week cycle for 4 cycles; 150 mg/day orally thereafter
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* male patients, \>/=18 years of age * former smoker (smoked \>/= 100 cigarettes in his lifetime and quit \>12 months before enrollment) * locally advanced (stage IIIb), metastatic (stage IV) or recurrent squamous non-small cell lung cancer * prior platinum-based therapy for advanced NSCLC * Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Exclusion criteria
* uncontrolled symptomatic central nervous system (CNS) metastases * prior therapy against epidermal growth factor receptor (EGFR) * \>1 prior chemotherapy for advanced/metastatic NSCLC * radiotherapy \<28 days prior to enrollment * history of melanoma at any time, or another malignancy in the last 5 years except for carcinoma in situ of the cervix, basal or squamous cell carcinoma of the skin, or surgically cured malignant neoplasias with a disease-free interval of \>5 years * not fully treated eye inflammation or infection, or predisposing conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Free From Disease Progression or Death at 6 Months | Month 6 | According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, progressive Disease (PD) is defined as: for Target Lesions - At least a 20 percent (%) 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 millimeter (mm). (Note: the appearance of one or more new lesions is also considered progression). For Non-Target Lesions - Unequivocal progression of existing non-target lesions. (Note: the appearance of one or more new lesions is also considered progression). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From randomization until death, assessed up to 18 months | Overall survival (OS) was defined as the interval (in days) between the date of randomization and death from any cause. Participants alive at the time of the analysis were censored at the date they were last known to be alive. OS was assessed using the Kaplan-Meier method. |
| Progression-free Survival (PFS) | From randomization until progressive disease or death, assessed up to 18 months | Progression-free Survival (PFS) was defined as the interval (in days) between the date of randomization and the first documentation of progressive disease or death from any cause. Participants alive and progression-free were considered as censored at the date of the last tumor assessment when the participant was known to be progression-free. Participants without post-baseline tumor assessment, but known to be alive, were censored at the time of randomization. PFS (days) = (Date of Event - Date of Randomization) + 1. PFS was assessed using the Kaplan-Meier method. Detailed definition of PD is provided in Outcome Measure 1. |
| Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) | From randomization until progressive disease or death, assessed up to 18 months | Best overall response (complete response \[CR\]/partial response \[PR\]) was defined as the best response recorded from the start of the treatment until disease progression (PD). Best response in this trial was defined as the best response observed at any post-treatment visits. According to RECIST Version 1.1, CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than \[\<\] 10 mm). No new lesions. PR was defined as greater than or equal to \[\>=\] 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. |
| Percentage of Participants With Disease Control | From randomization until progressive disease or death, assessed up to 18 months | Disease control was defined as PR, CR, or SD. Participants who did not achieve a CR or PR or SD were counted as non-responders in the analysis of disease control. According to RECIST Version 1.1, SD was defined as not qualifying for CR, PR, and PD. Detailed definitions of CR and PR are provided in Outcome Measure 4. |
| Duration of Response (DoR) | From randomization until progressive disease or death, assessed up to 18 months | Duration of response (DoR) was defined as the interval (in days) from first documentation of a response (CR/PR depending on which occurred first) to the date of the first documentation of disease progression or death from any cause. Participants presenting a response were considered as censored at the date of the last assessment with a documentation of non-progression. DoR (days) = (Date of PD/death - Date of CR/PR) + 1. Assessments were performed according to RECIST Version 1.1. DoR was assessed using the Kaplan-Meier method. Detailed definitions of CR and PR are provided in Outcome Measure 4. |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Erlotinib Participants received erlotinib at a dose of 150 mg/day orally as monotherapy, up to PD, death, or unacceptable toxicity. | 36 |
| Docetaxel and Erlotinib Participants received docetaxel at a dose of 75 mg/m\^2 as an intravenous infusion on Day 1 of each 3-week cycle, and erlotinib at a dose of 150 mg/day orally from Day 2 to Day 16 of each 3-week cycle for 4 cycles, administered in absence of PD, death, or unacceptable toxicity. Following the 4 cycles, erlotinib 150 mg/day was administered orally as monotherapy up to PD, death or unacceptable toxicity. | 37 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 26 | 27 |
| Overall Study | Lost to Follow-up | 3 | 4 |
| Overall Study | Randomized, but not treated | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 4 |
Baseline characteristics
| Characteristic | Docetaxel and Erlotinib | Total | Erlotinib |
|---|---|---|---|
| Age, Continuous | 65.9 years STANDARD_DEVIATION 8.1 | 67.2 years STANDARD_DEVIATION 8.2 | 68.4 years STANDARD_DEVIATION 8.3 |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 36 Participants | 72 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 32 / 36 | 35 / 37 |
| serious Total, serious adverse events | 15 / 36 | 10 / 37 |
Outcome results
Primary
Percentage of Participants Free From Disease Progression or Death at 6 Months
According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, progressive Disease (PD) is defined as: for Target Lesions - At least a 20 percent (%) 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 millimeter (mm). (Note: the appearance of one or more new lesions is also considered progression). For Non-Target Lesions - Unequivocal progression of existing non-target lesions. (Note: the appearance of one or more new lesions is also considered progression).
Time frame: Month 6
Population: FAS population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib | Percentage of Participants Free From Disease Progression or Death at 6 Months | 8.3 percentage of participants |
| Docetaxel and Erlotinib | Percentage of Participants Free From Disease Progression or Death at 6 Months | 8.1 percentage of participants |
Secondary
Duration of Response (DoR)
Duration of response (DoR) was defined as the interval (in days) from first documentation of a response (CR/PR depending on which occurred first) to the date of the first documentation of disease progression or death from any cause. Participants presenting a response were considered as censored at the date of the last assessment with a documentation of non-progression. DoR (days) = (Date of PD/death - Date of CR/PR) + 1. Assessments were performed according to RECIST Version 1.1. DoR was assessed using the Kaplan-Meier method. Detailed definitions of CR and PR are provided in Outcome Measure 4.
Time frame: From randomization until progressive disease or death, assessed up to 18 months
Population: FAS population. Here, number of participants analyzed signifies those participants who had a best overall response of CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib | Duration of Response (DoR) | NA months |
| Docetaxel and Erlotinib | Duration of Response (DoR) | 8.69 months |
Secondary
Overall Survival (OS)
Overall survival (OS) was defined as the interval (in days) between the date of randomization and death from any cause. Participants alive at the time of the analysis were censored at the date they were last known to be alive. OS was assessed using the Kaplan-Meier method.
Time frame: From randomization until death, assessed up to 18 months
Population: FAS population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib | Overall Survival (OS) | 5.61 months |
| Docetaxel and Erlotinib | Overall Survival (OS) | 8.95 months |
Secondary
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR)
Best overall response (complete response \[CR\]/partial response \[PR\]) was defined as the best response recorded from the start of the treatment until disease progression (PD). Best response in this trial was defined as the best response observed at any post-treatment visits. According to RECIST Version 1.1, CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than \[\<\] 10 mm). No new lesions. PR was defined as greater than or equal to \[\>=\] 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
Time frame: From randomization until progressive disease or death, assessed up to 18 months
Population: FAS population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib | Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) | 2.8 percentage of participants |
| Docetaxel and Erlotinib | Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) | 8.1 percentage of participants |
Secondary
Percentage of Participants With Disease Control
Disease control was defined as PR, CR, or SD. Participants who did not achieve a CR or PR or SD were counted as non-responders in the analysis of disease control. According to RECIST Version 1.1, SD was defined as not qualifying for CR, PR, and PD. Detailed definitions of CR and PR are provided in Outcome Measure 4.
Time frame: From randomization until progressive disease or death, assessed up to 18 months
Population: FAS population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib | Percentage of Participants With Disease Control | 41.7 percentage of participants |
| Docetaxel and Erlotinib | Percentage of Participants With Disease Control | 37.8 percentage of participants |
Secondary
Progression-free Survival (PFS)
Progression-free Survival (PFS) was defined as the interval (in days) between the date of randomization and the first documentation of progressive disease or death from any cause. Participants alive and progression-free were considered as censored at the date of the last tumor assessment when the participant was known to be progression-free. Participants without post-baseline tumor assessment, but known to be alive, were censored at the time of randomization. PFS (days) = (Date of Event - Date of Randomization) + 1. PFS was assessed using the Kaplan-Meier method. Detailed definition of PD is provided in Outcome Measure 1.
Time frame: From randomization until progressive disease or death, assessed up to 18 months
Population: FAS population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib | Progression-free Survival (PFS) | 2.33 months |
| Docetaxel and Erlotinib | Progression-free Survival (PFS) | 2.82 months |