Non-Small Cell Lung Cancer
Conditions
Brief summary
This study will assess the efficacy and safety of Avastin combined with first li ne paclitaxel-carboplatin (cohort 1) or second line Tarceva (cohort 2) in patien ts with non-squamous non-small cell lung cancer with asymptomatic untreated brai n metastasis. Two cohorts of patients will be studied; the first will receive Av astin 15mg/kg iv every 3 weeks combined with first line paclitaxel 200mg/m2 iv p lus carboplatin AUC6 iv every 3 weeks for a maximum of 6 cycles, and the second cohort will receive Avastin 15mg/kg iv every 3 weeks combined with second line T arceva 150mg/kg po.The anticipated time on study treatment is until disease prog ression, and the target sample size is 100-500 individuals.
Interventions
DRUGbevacizumab [Avastin]
15mg/kg iv every 3 weeks
DRUGcarboplatin
AUC6 iv every 3 weeks for 6 cycles
DRUGerlotinib [Tarceva]
150mg/day po
DRUGpaclitaxel
200mg/m2 iv every 3 weeks for 6 cycles
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_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; * stage IV non-squamous non-small cell lung cancer; * asymptomatic, untreated brain metastasis; * ECOG performance status 0-1.
Exclusion criteria
* previous treatment for brain metastasis; * history of migraine or epilepsy; * previous treatment with angiogenesis inhibitors; * for cohort 2, previous first line treatment with Avastin or Tarceva; * current or recent use of aspirin (\>325mg/day) or full-dose anticoagulants or thrombolytic agent for therapeutic purposes.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Progression-Free Survival (PFS) Without Disease Progression or Death at 6 Months | 6 months | Tumor progression was defined according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 as increase by at least 20% in the sum of the longest diameters of each target lesion, taking as a reference the smallest sum of the longest diameters, reported since the start of treatment, or appearance of one or more new lesions. PFS (investigator assessed) was defined as the time between the first dose of study treatment and the first event of progression or death by any cause. Participants without an event were censored the last time they were known to be progression free. PFS was analyzed using the Kaplan-Meier method in each treatment arm. |
| Percentage of Participants With Disease Progression or Death | Screening, Day 1 of Cycles 3 and 5 and every 2 cycles until end of treatment visit or disease progression or death up to 18 months after enrollment of last participant | Tumor progression was defined according to the RECIST criteria as increase by at least 20% in the sum of the longest diameters of each target lesion, taking as a reference the smallest sum of the longest diameters, reported since the start of treatment, or appearance of one or more new lesions. PFS (investigator assessed) was defined as the time between the first dose of study treatment and the first event of progression or death by any cause. Participants without an event were censored the last time they were known to be progression free. PFS was analyzed using the Kaplan-Meier method in each treatment arm. |
| Time to Disease Progression or Death | Screening, Day 1 of Cycles 3 and 5 and every 2 cycles until end of treatment visit or disease progression or death up to 18 months after enrollment of last participant | Tumor progression was defined as increase by at least 20% in the sum of the longest diameters of each target lesion, taking as a reference the smallest sum of the longest diameters, reported since the start of treatment, or appearance of one or more new lesions. Time to event was determined as the number of months between the first dose of study treatment and the first event of progression or death by any cause. PFS was analyzed using the Kaplan-Meier method in each treatment arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Died | Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 3 weeks up to 18 months or until death | — |
| Percentage of Participants Achieving a Best Overall Response of Complete Response or Partial Response as Assessed by the Investigator Using RECIST | Screening, Day 1 of Cycles 3 and 5 and every 2 cycles until end of treatment visit or disease progression or death up to 18 months after enrollment of last participant | Overall response defined as best response according to RECIST recorded from date of randomization until disease progression or recurrence. Complete Response (CR): disappearance of all target lesions; Partial response (PR): reduction by at least 30 percent (%) of sum of the longest diameters of each target lesion, taking initial sum of longest diameters as a reference. Participants with a missing response were considered non-responders. 95% CI for one sample binomial using Pearson-Clopper method. |
| Probability of Being Alive at 12 and 18 Months | Months 12 and 18 | — |
| Time to Death | Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 3 weeks up to 18 months or until death | Time to death was determined as the number of months between the first dose of study treatment and the event of death by any cause. Overall survival was analyzed using the Kaplan-Meier method. |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab+Paclitaxel+Carboplatin Participants received bevacizumab 15 mg/kg iv every 3 weeks until progression or unacceptable toxicity along with paclitaxel 200 mg/m\^2 iv every 3 weeks for 6 cycles and carboplatin: AUC 6.0 mg/mL/min iv every 3 weeks for 6 cycles. Bevacizumab was used in addition to standard first line chemotherapy. | 67 |
| Bevacizumab+Erlotinib Participants received bevacizumab 15 mg/kg iv every 3 weeks until progression or unacceptable toxicity along with erlotinib 150 mg/day administered as tablets orally until progression or unacceptable toxicity. Bevacizumab was used as second-line treatment in addition to erlotinib. | 24 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 7 | 6 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Disease Progression | 54 | 18 |
| Overall Study | Other | 5 | 0 |
Baseline characteristics
| Characteristic | Bevacizumab+Paclitaxel+Carboplatin | Bevacizumab+Erlotinib | Total |
|---|---|---|---|
| Age, Continuous | 60.37 years STANDARD_DEVIATION 8.31 | 54.17 years STANDARD_DEVIATION 9.73 | 58.74 years STANDARD_DEVIATION 9.07 |
| Sex: Female, Male Female | 21 Participants | 13 Participants | 34 Participants |
| Sex: Female, Male Male | 46 Participants | 11 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 67 / 67 | 24 / 24 |
| serious Total, serious adverse events | 27 / 67 | 7 / 24 |
Outcome results
Primary
Percentage of Participants Achieving Progression-Free Survival (PFS) Without Disease Progression or Death at 6 Months
Tumor progression was defined according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 as increase by at least 20% in the sum of the longest diameters of each target lesion, taking as a reference the smallest sum of the longest diameters, reported since the start of treatment, or appearance of one or more new lesions. PFS (investigator assessed) was defined as the time between the first dose of study treatment and the first event of progression or death by any cause. Participants without an event were censored the last time they were known to be progression free. PFS was analyzed using the Kaplan-Meier method in each treatment arm.
Time frame: 6 months
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab+Paclitaxel+Carboplatin | Percentage of Participants Achieving Progression-Free Survival (PFS) Without Disease Progression or Death at 6 Months | 56.5 percentage of participants |
| Bevacizumab+Erlotinib | Percentage of Participants Achieving Progression-Free Survival (PFS) Without Disease Progression or Death at 6 Months | 57.2 percentage of participants |
Primary
Percentage of Participants With Disease Progression or Death
Tumor progression was defined according to the RECIST criteria as increase by at least 20% in the sum of the longest diameters of each target lesion, taking as a reference the smallest sum of the longest diameters, reported since the start of treatment, or appearance of one or more new lesions. PFS (investigator assessed) was defined as the time between the first dose of study treatment and the first event of progression or death by any cause. Participants without an event were censored the last time they were known to be progression free. PFS was analyzed using the Kaplan-Meier method in each treatment arm.
Time frame: Screening, Day 1 of Cycles 3 and 5 and every 2 cycles until end of treatment visit or disease progression or death up to 18 months after enrollment of last participant
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab+Paclitaxel+Carboplatin | Percentage of Participants With Disease Progression or Death | 89.6 percentage of participants |
| Bevacizumab+Erlotinib | Percentage of Participants With Disease Progression or Death | 91.7 percentage of participants |
Primary
Time to Disease Progression or Death
Tumor progression was defined as increase by at least 20% in the sum of the longest diameters of each target lesion, taking as a reference the smallest sum of the longest diameters, reported since the start of treatment, or appearance of one or more new lesions. Time to event was determined as the number of months between the first dose of study treatment and the first event of progression or death by any cause. PFS was analyzed using the Kaplan-Meier method in each treatment arm.
Time frame: Screening, Day 1 of Cycles 3 and 5 and every 2 cycles until end of treatment visit or disease progression or death up to 18 months after enrollment of last participant
Population: ITT Population; only participants with progression or death were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab+Paclitaxel+Carboplatin | Time to Disease Progression or Death | 6.7 months |
| Bevacizumab+Erlotinib | Time to Disease Progression or Death | 6.3 months |
Secondary
Percentage of Participants Achieving a Best Overall Response of Complete Response or Partial Response as Assessed by the Investigator Using RECIST
Overall response defined as best response according to RECIST recorded from date of randomization until disease progression or recurrence. Complete Response (CR): disappearance of all target lesions; Partial response (PR): reduction by at least 30 percent (%) of sum of the longest diameters of each target lesion, taking initial sum of longest diameters as a reference. Participants with a missing response were considered non-responders. 95% CI for one sample binomial using Pearson-Clopper method.
Time frame: Screening, Day 1 of Cycles 3 and 5 and every 2 cycles until end of treatment visit or disease progression or death up to 18 months after enrollment of last participant
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab+Paclitaxel+Carboplatin | Percentage of Participants Achieving a Best Overall Response of Complete Response or Partial Response as Assessed by the Investigator Using RECIST | 62.7 percentage of participants |
| Bevacizumab+Erlotinib | Percentage of Participants Achieving a Best Overall Response of Complete Response or Partial Response as Assessed by the Investigator Using RECIST | 12.5 percentage of participants |
Secondary
Percentage of Participants Who Died
Time frame: Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 3 weeks up to 18 months or until death
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab+Paclitaxel+Carboplatin | Percentage of Participants Who Died | 83.6 percentage of participants |
| Bevacizumab+Erlotinib | Percentage of Participants Who Died | 91.7 percentage of participants |
Secondary
Probability of Being Alive at 12 and 18 Months
Time frame: Months 12 and 18
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab+Paclitaxel+Carboplatin | Probability of Being Alive at 12 and 18 Months | 12 Months | 64.2 percent |
| Bevacizumab+Paclitaxel+Carboplatin | Probability of Being Alive at 12 and 18 Months | 18 Months | 43.3 percent |
| Bevacizumab+Erlotinib | Probability of Being Alive at 12 and 18 Months | 18 Months | 41.7 percent |
| Bevacizumab+Erlotinib | Probability of Being Alive at 12 and 18 Months | 12 Months | 50.0 percent |
Secondary
Time to Death
Time to death was determined as the number of months between the first dose of study treatment and the event of death by any cause. Overall survival was analyzed using the Kaplan-Meier method.
Time frame: Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 3 weeks up to 18 months or until death
Population: ITT Population; only participants with an event of death were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab+Paclitaxel+Carboplatin | Time to Death | 16.0 months |
| Bevacizumab+Erlotinib | Time to Death | 12.0 months |