Non-Small Cell Lung Cancer
Conditions
Brief summary
This study will evaluate the efficacy and safety of sequential administration of Tarceva and gemcitabine/platinum chemotherapy in patients with stage IIIb/IV non-small cell lung cancer. Patients will be randomized to receive Tarceva (150 mg po) or placebo on days 15-28 of a 4 week cycle of intravenous platinum-based chemotherapy, for a total of 6 cycles. The anticipated time on study treatment is until disease progression or unacceptable toxicity.
Interventions
DRUGcisplatin
75 mg/m2 iv Day 1 of each 4.wek cycle, 6 cycles; or carboplatin
DRUGcarboplatin
5 x AUC iv Day 1 of each 4.week cycle, 6 cycles; or cisplatin
DRUGerlotinib [Tarceva]
150 mg orally daily Days 15 to 28 of each 4-week cycle for 6 cycles, followed by 150 mg orally daily
DRUGplacebo
orally daily Days 15 to 28 of each 4-week cycle for 6 cycles, followed by daily oral application
DRUGgemcitabine
1250 mg/m2 iv Days 1 and 8 of each 4-week cycle, 6 cycles
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* adult patients, \>=18 years of age; * histologically documented advanced or recurrent stage IIIB or IV non-small cell lung cancer; * measurable disease; * no previous chemotherapy for non-small cell lung cancer.
Exclusion criteria
* unstable systemic disease; * any other malignancies in the last 5 years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Non-Progression at Week 8 as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) | Week 8 | Non-progression defined as documented best overall tumor response of complete response (CR), partial response (PR), or stable disease (SD; where SD was maintained for greater than \[\>\]8 weeks) per RECIST. Investigator's assessment of response used in all analyses. CR equals (=)disappearance of all target lesions; PR=at least a 30 percent (%) decrease in sum of longest diameter (LD) of target lesions, taking as reference the baseline sum LD; SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference smallest sum LD since treatment started. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Confirmed CR or PR as Assessed by RECIST | Screening/Baseline, Day 22 of Cycles 2, 4 and 6 and every 8 weeks in Post-Study and Off-Study Phases | CR=disappearance of all target lesions; PR=at least a 30% decrease in sum of LD of target lesions, taking as reference the baseline sum LD. |
| Duration of Response | Screening/Baseline, Day 22 of Cycles 2, 4 and 6 and every 8 weeks in Post-Study and Off-study Phases | Duration of Response was defined similarly for complete responders and partial responders. CR was defined as the date CR was first recorded to the date on which PD was first noted or date of death. PR was defined as the date the first PR was recorded to the date of the first observation of PD or date of death. |
| Percentage of Participants With Non-Progression at Week 16 as Assessed by RECIST | Week 16 | Non-progression defined as documented best overall tumor response of CR, PR, or SD (where SD was maintained for \>16 weeks) per RECIST. |
| Progression-Free Survival (PFS) | Screening/Baseline, Day 22 of Cycles 2, 4 and 6 and every 8 weeks in Post-Study and Off-Study Phases | PFS was defined as the interval between the day of randomization and the date of first documentation of progressive disease or date of death, whichever came first. |
| Overall Survival | Date of randomization until date of death or date of last follow-up assessment | Overall Survival (OS) was defined as the time from the date of randomization to the date of death, regardless of the cause of death. Participants who were alive at the time of the analysis were censored at the date of the last follow-up assessment. |
| Time to Progression | Screening/Baseline, Day 22 of Cycles 2, 4 and 6 and every 8 weeks in Post-Study and Off-Study Phases | Time to progression was defined as the interval between the day of randomization and the first documentation of PD. Participants who were withdrawn from the study without documented progression and for whom there exists CRF evidence that evaluations have been made, were censored at 1) the date of the last tumor assessment, 2) last date in the drug log, or 3) last date of follow-up when the participant was known to be progression free, whichever was last. Participants without post-baseline tumor assessments but known to be alive were censored at the time of randomization. |
Countries
Australia, China, Hong Kong, Indonesia, Philippines, South Korea, Taiwan, Thailand
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Plus Chemotherapy Participants received placebo tablets, PO, on Days 15 to 28 of a 4-week cycle; participants also received platinum-based doublet chemotherapy: gemcitabine 1250 mg/m\^2 via intravenous (IV) infusion on Days 1 and 8 and either cisplatin (75 mg/m\^2) or carboplatin (5 x AUC), via IV infusion, per investigator discretion, on Day 1. Participants received study drugs for a maximum of 6 cycles until disease progression, unacceptable toxicity or death. After 6 cycles, participants may have continued to receive placebo tablets daily. | 78 |
| Erlotinib Plus Chemotherapy Participants received erlotinib tablets, 150 mg per day, PO on Days 15 to 28 of every 4-week cycle; participants also received platinum-based doublet chemotherapy: gemcitabine 1250 mg/m\^2 via IV infusion on Days 1 and 8 and either cisplatin (75 mg/m\^2) or carboplatin (5 x AUC), via IV infusion, per investigator discretion, on Day 1. Participants received study drugs for a maximum of 6 cycles until disease progression, unacceptable toxicity or death. After 6 cycles, participants may have continued to receive erlotinib monotherapy, 150 mg daily. | 76 |
| Total | 154 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 5 |
| Overall Study | Death | 2 | 2 |
| Overall Study | Disease progression | 31 | 22 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Other | 5 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 4 |
Baseline characteristics
| Characteristic | Placebo Plus Chemotherapy | Erlotinib Plus Chemotherapy | Total |
|---|---|---|---|
| Age, Continuous | 56.5 years STANDARD_DEVIATION 10.06 | 56.4 years STANDARD_DEVIATION 10.43 | 56.45 years STANDARD_DEVIATION 10.245 |
| Sex: Female, Male Female | 24 Participants | 22 Participants | 46 Participants |
| Sex: Female, Male Male | 54 Participants | 54 Participants | 108 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 74 / 79 | 73 / 74 |
| serious Total, serious adverse events | 17 / 79 | 17 / 74 |
Outcome results
Primary
Percentage of Participants With Non-Progression at Week 8 as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST)
Non-progression defined as documented best overall tumor response of complete response (CR), partial response (PR), or stable disease (SD; where SD was maintained for greater than \[\>\]8 weeks) per RECIST. Investigator's assessment of response used in all analyses. CR equals (=)disappearance of all target lesions; PR=at least a 30 percent (%) decrease in sum of longest diameter (LD) of target lesions, taking as reference the baseline sum LD; SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference smallest sum LD since treatment started.
Time frame: Week 8
Population: FAS; for analysis, participants were assigned the treatment group to which they were randomized, regardless of the treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Plus Chemotherapy | Percentage of Participants With Non-Progression at Week 8 as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) | 76.9 percentage of participants |
| Erlotinib Plus Chemotherapy | Percentage of Participants With Non-Progression at Week 8 as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) | 80.3 percentage of participants |
95% CI: [-10.3, 17]
Secondary
Duration of Response
Duration of Response was defined similarly for complete responders and partial responders. CR was defined as the date CR was first recorded to the date on which PD was first noted or date of death. PR was defined as the date the first PR was recorded to the date of the first observation of PD or date of death.
Time frame: Screening/Baseline, Day 22 of Cycles 2, 4 and 6 and every 8 weeks in Post-Study and Off-study Phases
Population: FAS; only participants with CR or PR were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Plus Chemotherapy | Duration of Response | 24.1 weeks |
| Erlotinib Plus Chemotherapy | Duration of Response | 38.4 weeks |
p-value: 0.0075Log Rank
p-value: 0.009995% CI: [0.22, 0.81]Wald test
Secondary
Overall Survival
Overall Survival (OS) was defined as the time from the date of randomization to the date of death, regardless of the cause of death. Participants who were alive at the time of the analysis were censored at the date of the last follow-up assessment.
Time frame: Date of randomization until date of death or date of last follow-up assessment
Population: FAS Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Plus Chemotherapy | Overall Survival | 75.7 weeks |
| Erlotinib Plus Chemotherapy | Overall Survival | 74.1 weeks |
p-value: 0.5991Log Rank
p-value: 0.377495% CI: [0.58, 1.23]Wald test
Secondary
Percentage of Participants With Confirmed CR or PR as Assessed by RECIST
CR=disappearance of all target lesions; PR=at least a 30% decrease in sum of LD of target lesions, taking as reference the baseline sum LD.
Time frame: Screening/Baseline, Day 22 of Cycles 2, 4 and 6 and every 8 weeks in Post-Study and Off-Study Phases
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Plus Chemotherapy | Percentage of Participants With Confirmed CR or PR as Assessed by RECIST | 24.4 percentage of participants |
| Erlotinib Plus Chemotherapy | Percentage of Participants With Confirmed CR or PR as Assessed by RECIST | 36.8 percentage of participants |
95% CI: [-2.7, 27.7]
Secondary
Percentage of Participants With Non-Progression at Week 16 as Assessed by RECIST
Non-progression defined as documented best overall tumor response of CR, PR, or SD (where SD was maintained for \>16 weeks) per RECIST.
Time frame: Week 16
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Plus Chemotherapy | Percentage of Participants With Non-Progression at Week 16 as Assessed by RECIST | 53.8 percentage of participants |
| Erlotinib Plus Chemotherapy | Percentage of Participants With Non-Progression at Week 16 as Assessed by RECIST | 64.5 percentage of participants |
95% CI: [-5.6, 26.8]
Secondary
Progression-Free Survival (PFS)
PFS was defined as the interval between the day of randomization and the date of first documentation of progressive disease or date of death, whichever came first.
Time frame: Screening/Baseline, Day 22 of Cycles 2, 4 and 6 and every 8 weeks in Post-Study and Off-Study Phases
Population: FAS Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Plus Chemotherapy | Progression-Free Survival (PFS) | 23.4 weeks |
| Erlotinib Plus Chemotherapy | Progression-Free Survival (PFS) | 30.4 weeks |
p-value: 0.0001Log Rank
p-value: <0.000195% CI: [0.33, 0.68]Wald test
Secondary
Time to Progression
Time to progression was defined as the interval between the day of randomization and the first documentation of PD. Participants who were withdrawn from the study without documented progression and for whom there exists CRF evidence that evaluations have been made, were censored at 1) the date of the last tumor assessment, 2) last date in the drug log, or 3) last date of follow-up when the participant was known to be progression free, whichever was last. Participants without post-baseline tumor assessments but known to be alive were censored at the time of randomization.
Time frame: Screening/Baseline, Day 22 of Cycles 2, 4 and 6 and every 8 weeks in Post-Study and Off-Study Phases
Population: FAS Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Plus Chemotherapy | Time to Progression | 24.1 weeks |
| Erlotinib Plus Chemotherapy | Time to Progression | 31.4 weeks |
p-value: 0.0004Log Rank
p-value: 0.000195% CI: [0.33, 0.7]Wald Test