Non-Small Cell Lung Cancer
Conditions
Keywords
Tarceva, Lung Cancer, NSCLC
Brief summary
This is a Phase II, double-blind, randomized, multicenter trial designed to preliminarily evaluate the activity and safety of treatment with MetMAb + erlotinib versus erlotinib + placebo in second- and third-line Non-Small Cell Lung Cancer (NSCLC). Up to 180 patients will be randomized in a 1:1 ratio to one of the two treatment arms.
Interventions
DRUGErlotinib HCl
Erlotinib 150 mg oral dose once daily.
DRUGMetMAb
MetMab (a monovalent antagonist antibody to the receptor MET) 15 mg/kg in 250 CC 0.9% saline intravenous infusion every 3 weeks.
Placebo Intravenous infusion every 3 weeks.
Sponsors
Genentech, Inc.
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
Patients must meet the following criteria for study entry: * Histologically confirmed NSCLC * Availability of a tumor specimen * Recurrent or progressive disease following at least one chemo containing regimen for Stage IIIB/IV disease * Measurable disease in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) * At least one measurable lesion on a pre-treatment 18-fluorodeoxyglcose-positron emission tomography (FDG-PET) scan that is also a target lesion on computed tomography (CT) according to RECIST
Exclusion criteria
* More than two prior treatments for Stage IIIB/IV * More than 30 days of exposure to an investigational or marketed agent that can act by EGFR inhibition, or a known epidermal growth factor receptor (EGFR)-related toxicity resulting in dose modifications * Chemotherapy, biologic therapy, radiotherapy or investigational drug within 28 days prior to randomization * Untreated and/or active (progressing or requiring anticonvulsants or corticosteroids for symptomatic control) central nervous system (CNS) metastasis * History of serious systemic disease within the past 6 months prior to randomization * Uncontrolled diabetes * Major surgical procedure or significant traumatic injury within 28 days prior to randomization * Anticipation of need for a major surgical procedure during the course of the study * Local palliative radiotherapy within 7 days prior to randomization or persistent adverse effects from radiotherapy that have not been resolved to Grade II or less prior to randomization * Symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | Time from randomization to the first occurrence of progression/relapse or death on study. (Up to 20 months) | Progression-free survival was defined as the time from randomization to the first occurrence of progression or relapse (as per Response Evaluation Criteria in Solid Tumors (RECIST 1.0) and assessed by the site radiologist or investigator) or death on study from any cause (within 30 days of last treatment). |
| Progression-free Survival in Patients With Met Diagnostic-Positive Tumors | Time from randomization to the first occurrence of progression/relapse or death on study. (Up to 20 months) | Progression-free survival (PFS) in participants with Met Diagnostic-Positive tumors as determined by immunohistochemistry. PFS was defined as the time from randomization to the first occurrence of progression or relapse (as per Response Evaluation Criteria in Solid Tumors (RECIST 1.0) and assessed by the site radiologist or investigator) or death on study from any cause (within 30 days of last treatment). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response | Start of treatment until disease progression/recurrence or death on study. (Up to 20 months) | Objective response (partial and complete response as determined using RECIST 1.0). Partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum longest diameter. Complete response was defined as disappearance of all target lesions. |
| Percentage of Participants With Objective Response in Patients With Met Diagnostic-Positive Tumors | Start of treatment until disease progression/recurrence or death on study. (Up to 20 months) | Objective response (OR); partial and complete response as determined using RECIST 1.0 in patients with Met Diagnostic-Positive Tumors as determined by immunohistochemistry. Partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum longest diameter. Complete response was defined as disappearance of all target lesions. |
| Duration of Overall Response | Date of initial response until date of progression or death on study. (Up to 20 months) | — |
Participant flow
Pre-assignment details
Twenty-seven patients in the placebo + erlotinib arm with disease progression in the blinded treatment stage elected to receive MetMAb + erlotinib in the optional open-label phase of the study.
Participants by arm
| Arm | Count |
|---|---|
| MetMAb + Erlotinib MetMab 15 mg/kg intravenous (IV) infusion every 3 weeks + Erlotinib 150 mg orally once daily until progression of disease or unacceptable toxicity. | 69 |
| Placebo + Erlotinib Placebo IV infusion every 3 weeks + Erlotinib 150 mg orally daily until progression of disease or unacceptable toxicity. | 68 |
| Total | 137 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 3 |
| Overall Study | Death | 2 | 5 |
| Overall Study | Disease progression | 42 | 50 |
| Overall Study | Physician Decision | 6 | 6 |
| Overall Study | Sponsor's decision to terminate study | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 2 |
Baseline characteristics
| Characteristic | MetMAb + Erlotinib | Placebo + Erlotinib | Total |
|---|---|---|---|
| Age, Continuous | 63.6 years STANDARD_DEVIATION 9.4 | 62.7 years STANDARD_DEVIATION 10.6 | 63.1 years STANDARD_DEVIATION 10 |
| Sex: Female, Male Female | 29 Participants | 26 Participants | 55 Participants |
| Sex: Female, Male Male | 40 Participants | 42 Participants | 82 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 68 / 69 | 67 / 67 |
| serious Total, serious adverse events | 29 / 69 | 22 / 67 |
Outcome results
Primary
Progression-free Survival
Progression-free survival was defined as the time from randomization to the first occurrence of progression or relapse (as per Response Evaluation Criteria in Solid Tumors (RECIST 1.0) and assessed by the site radiologist or investigator) or death on study from any cause (within 30 days of last treatment).
Time frame: Time from randomization to the first occurrence of progression/relapse or death on study. (Up to 20 months)
Population: All randomized intent-to-treat patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MetMAb + Erlotinib | Progression-free Survival | 2.2 months |
| Placebo + Erlotinib | Progression-free Survival | 2.6 months |
Comparison: The null hypothesis is that there is no difference in PFS between MetMab + Erlotinib and Placebo + Erlotinib. The alternate hypothesis is that MetMab + Erlotinib would have prolonged PFS compared with Placebo + Erlotinib.p-value: 0.687395% CI: [0.727, 1.622]Log Rank
Primary
Progression-free Survival in Patients With Met Diagnostic-Positive Tumors
Progression-free survival (PFS) in participants with Met Diagnostic-Positive tumors as determined by immunohistochemistry. PFS was defined as the time from randomization to the first occurrence of progression or relapse (as per Response Evaluation Criteria in Solid Tumors (RECIST 1.0) and assessed by the site radiologist or investigator) or death on study from any cause (within 30 days of last treatment).
Time frame: Time from randomization to the first occurrence of progression/relapse or death on study. (Up to 20 months)
Population: All randomized intent-to-treat patients with Met Diagnostic-Positive tumors.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MetMAb + Erlotinib | Progression-free Survival in Patients With Met Diagnostic-Positive Tumors | 2.9 months |
| Placebo + Erlotinib | Progression-free Survival in Patients With Met Diagnostic-Positive Tumors | 1.5 months |
Comparison: The null hypothesis is that there is no difference in PFS between MetMab + Erlotinib and Placebo + Erlotinib. The alternate hypothesis is that MetMab + Erlotinib would have prolonged PFS compared with Placebo + Erlotinib.p-value: 0.041895% CI: [0.284, 0.986]Log Rank
Secondary
Duration of Overall Response
Time frame: Date of initial response until date of progression or death on study. (Up to 20 months)
Population: All randomized intent-to-treat patients. Analyses of duration of response were not performed because of the small number of patients with objective responses.
Secondary
Percentage of Participants With Objective Response
Objective response (partial and complete response as determined using RECIST 1.0). Partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum longest diameter. Complete response was defined as disappearance of all target lesions.
Time frame: Start of treatment until disease progression/recurrence or death on study. (Up to 20 months)
Population: All randomized intent-to-treat patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MetMAb + Erlotinib | Percentage of Participants With Objective Response | 5.8 Percentage of participants |
| Placebo + Erlotinib | Percentage of Participants With Objective Response | 4.4 Percentage of participants |
Comparison: The null hypothesis is that there is no difference in Objective Response between MetMab + Erlotinib and Placebo + Erlotinib. The alternate hypothesis is that MetMab + Erlotinib would have better Objective Response compared with Placebo + Erlotinib.p-value: 0.7101Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Objective Response in Patients With Met Diagnostic-Positive Tumors
Objective response (OR); partial and complete response as determined using RECIST 1.0 in patients with Met Diagnostic-Positive Tumors as determined by immunohistochemistry. Partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum longest diameter. Complete response was defined as disappearance of all target lesions.
Time frame: Start of treatment until disease progression/recurrence or death on study. (Up to 20 months)
Population: All randomized intent-to-treat patients with Met Diagnostic-positive tumors.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MetMAb + Erlotinib | Percentage of Participants With Objective Response in Patients With Met Diagnostic-Positive Tumors | 8.6 Percentage of participants |
| Placebo + Erlotinib | Percentage of Participants With Objective Response in Patients With Met Diagnostic-Positive Tumors | 3.2 Percentage of participants |
Comparison: The null hypothesis is that there is no difference in Objective Response between MetMab + Erlotinib and Placebo + Erlotinib. The alternate hypothesis is that MetMab + Erlotinib would have better Objective Response compared with Placebo + Erlotinibp-value: 0.3671Cochran-Mantel-Haenszel