Non-Small Cell Lung Cancer
Conditions
Brief summary
This 2 arm study will compare the efficacy and safety of Tarceva plus Avastin, and chemotherapy plus Avastin, in the first-line treatment of patients with advanced non-small cell lung cancer. Patients will be randomized to receive either Tarceva 150mg p.o. daily plus Avastin 15mg/kg i.v. every 3 weeks, or standard platinum-based chemotherapy (4-6 cycles) plus Avastin. The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.
Interventions
DRUGBevacizumab
15 mg/kg, IV, Day 1 of Cycles 1 through 7
DRUGStandard platinum-based chemotherapy
At the discretion of the investigator
DRUGErlotinib
150 mg, PO, daily
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
* adult patients, \>=18 years of age; * advanced (stage IIIb and IV) non-small cell lung cancer; * measurable disease; * ECOG PS 0-1.
Exclusion criteria
* prior chemotherapy or treatment with another systemic anti-cancer agent; * radiotherapy within 4 weeks prior to first dose of study treatment; * CNS metastases; * other malignancies in past 5 years, except for adequately treated cancer in situ of the cervix, basal or squamous cell skin cancer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Disease Progression or Death | Screening, end of every 2nd cycle through Cycle 8 (21-day cycles), and every 12 weeks thereafter until the end of study and final analysis up to a maximum of 42 months. | Progression-free survival (PFS) was defined as the time from randomization to disease progression or death, from any cause. Progressive disease (PD) was defined according to Response Criteria in Solid Tumors (RECIST) version (V) 1.0. For target lesions (TLs), progressive disease (PD) was defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded since the start of treatment. For non-target lesions (NTLs), PD was defined as unequivocal progression of existing NTLs. Participants were censored at the date of last post-baseline (BL) tumor assessment where non-progression was documented. If no post-BL tumor assessment was available, the participant was censored at date of randomization. |
| PFS | Screening, end of every 2nd cycle through Cycle 8 (21-day cycles), and every 12 weeks thereafter until the end of study and final analysis up to a maximum of 42 months. | The median time, in weeks, from randomization to PFS event. Participants were censored at the date of last post-BL tumor assessment where non-progression was documented. If no post-BL tumor assessment was available, the participant was censored at date of randomization. PFS was estimated using Kaplan-Meier methodology. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Died | Screening, Days 1, 8, and 21 of Cycles 1-8 (21-day cycles), and every 12 weeks thereafter until the end of study and final analysis up to a maximum of 42 months. | Overall survival (OS) was defined as the time from randomization to the date of death, due to any cause. Participants were censored at final analysis at the date the participant was last known to be alive. |
| OS | Screening, Days 1, 8, and 21 of Cycles 1-8 (21-day cycles), and every 12 weeks thereafter until the end of study and final analysis up to a maximum of 42 months. | The median time, in months, from randomization to OS event. Participants were censored at final analysis at the date the participant was last known to be alive. |
| Percentage of Participants With a Best Overall Response (BOR) of Confirmed Complete Response (CR) or Partial Response (PR) According to RECIST V 1.0 | Screening, end of every 2nd cycle through Cycle 8 (21-day cycles), and every 12 weeks thereafter until the end of study and final analysis up to a maximum of 42 months. | BOR was defined as the best response recorded from randomization until disease progression/recurrence or death, taking as reference for PD the smallest measurement (nadir) recorded since treatment started. Assignment of PR of CR required confirmation of tumor measurement changes by repeat assessments performed no less than 4 weeks after criteria for response was first met. For TLs, CR was defined as the disappearance of all TLs; and PR was defined as at least a 30% decrease in the SLD of the TLs, taking BL SLD as reference. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels. The 95% CI for one sample binomial was calculated using the Pearson-Clopper method. |
| Percentage of Participants With Disease Control According to RECIST V 1.0 | Screening, end of every 2nd cycle through Cycle 8 (21-day cycles), and every 12 weeks thereafter until the end of study and final analysis, 12 months after the last participant's 1st visit | Disease control was defined as a BOR of CR, PR, or SD according to RECIST V 1.0 for at least 4 weeks at any time during randomized treatment or disease stabilization, after study entry. Participants without a post-BL assessment of response were considered as having no disease control. The 95% CI for the one sample binomial was calculated using the Pearson-Clopper method. |
Countries
Australia, Belgium, France, Italy, Lithuania, Netherlands, Poland, Romania, Singapore, South Korea, Spain, Taiwan, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab + Chemotherapy Participants received bevacizumab 15 mg/kg, IV, on Day 1 of Cycles 1 through 7 (21 day cycles) until disease progression, unacceptable toxicity, death, or withdrawal. Participants also received a maximum of up to 6 cycles (12-18 weeks) with EITHER a gemicitabine/cisplatin regimen (gemcitabine 1250 mg/m\^2, IV, on Days 1 and 8 of up to 6 cycles of 21 days, and cisplatin 80 mg/m\^2, IV, on Day 1 of up to 6 cycles of 21 days); OR a carboplatin/paclitaxel regimen (paclitaxel 200 mg/m\^2, IV, followed by carboplatin 6 mg/mL\*min on Day 1 of up to 6 cycles of 21 days). The chemotherapy regimen and number of cycles was up to the discretion of the investigator. | 61 |
| Bevacizumab + Erlotinib Participants received bevacizumab 15 mg/kg, IV, on Day 1 of Cycles 1 through 7 (21 day cycles) until disease progression, unacceptable toxicity, death, or withdrawal. Participants also received erlotinib 150 mg tablets, PO, daily until disease progression, unacceptable toxicity, death, or withdrawal. | 63 |
| Total | 124 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 4 |
| Overall Study | Death | 3 | 2 |
| Overall Study | Lack of Efficacy | 42 | 41 |
| Overall Study | Other | 4 | 10 |
| Overall Study | Refused Treatment | 5 | 6 |
| Overall Study | Violation of Selection Criteria | 2 | 0 |
Baseline characteristics
| Characteristic | Bevacizumab + Chemotherapy | Bevacizumab + Erlotinib | Total |
|---|---|---|---|
| Age, Continuous | 58.0 years STANDARD_DEVIATION 9.55 | 61.0 years STANDARD_DEVIATION 10.94 | 59.53 years STANDARD_DEVIATION 10.34 |
| Sex: Female, Male Female | 25 Participants | 26 Participants | 51 Participants |
| Sex: Female, Male Male | 36 Participants | 37 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 58 / 60 | 60 / 63 |
| serious Total, serious adverse events | 22 / 60 | 17 / 63 |
Outcome results
Primary
Percentage of Participants With Disease Progression or Death
Progression-free survival (PFS) was defined as the time from randomization to disease progression or death, from any cause. Progressive disease (PD) was defined according to Response Criteria in Solid Tumors (RECIST) version (V) 1.0. For target lesions (TLs), progressive disease (PD) was defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded since the start of treatment. For non-target lesions (NTLs), PD was defined as unequivocal progression of existing NTLs. Participants were censored at the date of last post-baseline (BL) tumor assessment where non-progression was documented. If no post-BL tumor assessment was available, the participant was censored at date of randomization.
Time frame: Screening, end of every 2nd cycle through Cycle 8 (21-day cycles), and every 12 weeks thereafter until the end of study and final analysis up to a maximum of 42 months.
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + Chemotherapy | Percentage of Participants With Disease Progression or Death | 72.1 percentage of participants |
| Bevacizumab + Erlotinib | Percentage of Participants With Disease Progression or Death | 76.2 percentage of participants |
Primary
PFS
The median time, in weeks, from randomization to PFS event. Participants were censored at the date of last post-BL tumor assessment where non-progression was documented. If no post-BL tumor assessment was available, the participant was censored at date of randomization. PFS was estimated using Kaplan-Meier methodology.
Time frame: Screening, end of every 2nd cycle through Cycle 8 (21-day cycles), and every 12 weeks thereafter until the end of study and final analysis up to a maximum of 42 months.
Population: FAS; only participants with an event (disease progression or death) were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + Chemotherapy | PFS | 34.6 weeks |
| Bevacizumab + Erlotinib | PFS | 23.4 weeks |
p-value: 0.80695% CI: [0.7, 1.59]Log Rank
Secondary
OS
The median time, in months, from randomization to OS event. Participants were censored at final analysis at the date the participant was last known to be alive.
Time frame: Screening, Days 1, 8, and 21 of Cycles 1-8 (21-day cycles), and every 12 weeks thereafter until the end of study and final analysis up to a maximum of 42 months.
Population: FAS; only participants who died were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + Chemotherapy | OS | NA months |
| Bevacizumab + Erlotinib | OS | 16.4 months |
p-value: 0.406395% CI: [0.75, 2.05]Log Rank
Secondary
Percentage of Participants Who Died
Overall survival (OS) was defined as the time from randomization to the date of death, due to any cause. Participants were censored at final analysis at the date the participant was last known to be alive.
Time frame: Screening, Days 1, 8, and 21 of Cycles 1-8 (21-day cycles), and every 12 weeks thereafter until the end of study and final analysis up to a maximum of 42 months.
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + Chemotherapy | Percentage of Participants Who Died | 45.9 percentage of participants |
| Bevacizumab + Erlotinib | Percentage of Participants Who Died | 52.4 percentage of participants |
Secondary
Percentage of Participants With a Best Overall Response (BOR) of Confirmed Complete Response (CR) or Partial Response (PR) According to RECIST V 1.0
BOR was defined as the best response recorded from randomization until disease progression/recurrence or death, taking as reference for PD the smallest measurement (nadir) recorded since treatment started. Assignment of PR of CR required confirmation of tumor measurement changes by repeat assessments performed no less than 4 weeks after criteria for response was first met. For TLs, CR was defined as the disappearance of all TLs; and PR was defined as at least a 30% decrease in the SLD of the TLs, taking BL SLD as reference. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels. The 95% CI for one sample binomial was calculated using the Pearson-Clopper method.
Time frame: Screening, end of every 2nd cycle through Cycle 8 (21-day cycles), and every 12 weeks thereafter until the end of study and final analysis up to a maximum of 42 months.
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + Chemotherapy | Percentage of Participants With a Best Overall Response (BOR) of Confirmed Complete Response (CR) or Partial Response (PR) According to RECIST V 1.0 | 44.3 percentage of participants |
| Bevacizumab + Erlotinib | Percentage of Participants With a Best Overall Response (BOR) of Confirmed Complete Response (CR) or Partial Response (PR) According to RECIST V 1.0 | 27.0 percentage of participants |
p-value: 0.044495% CI: [-34.8, 0.3]Chi-squared
Secondary
Percentage of Participants With Disease Control According to RECIST V 1.0
Disease control was defined as a BOR of CR, PR, or SD according to RECIST V 1.0 for at least 4 weeks at any time during randomized treatment or disease stabilization, after study entry. Participants without a post-BL assessment of response were considered as having no disease control. The 95% CI for the one sample binomial was calculated using the Pearson-Clopper method.
Time frame: Screening, end of every 2nd cycle through Cycle 8 (21-day cycles), and every 12 weeks thereafter until the end of study and final analysis, 12 months after the last participant's 1st visit
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + Chemotherapy | Percentage of Participants With Disease Control According to RECIST V 1.0 | 85.2 percentage of participants |
| Bevacizumab + Erlotinib | Percentage of Participants With Disease Control According to RECIST V 1.0 | 73.0 percentage of participants |
p-value: 0.094495% CI: [-27.3, 2.8]Chi-squared