Non-Small Cell Lung Cancer
Conditions
Keywords
NSCLC, Avastin, Tarceva, Lung Cancer
Brief summary
This is a Phase III, multicenter, placebo-controlled, double-blind, randomized study. Approximately 650 patients will be randomized in a 1:1 ratio to one of two treatment arms.
Interventions
DRUGbevacizumab
intravenous infusion of bevacizumab at a dose of 15 mg/kg on the first day of each 3-week cycle
DRUGerlotinib HCl
oral erlotinib HCl 150 mg/day orally
DRUGplacebo
intravenous infusion of placebo at a dose of 15 mg/kg on the first day of each 3-week cycle
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
* Signed written informed consent * Cytologically or histologically confirmed NSCLC * Clinical or radiographic progression during or after first-line chemotherapy or chemoradiotherapy for NSCLC * Consent to provide archival tissue for analysis is required for participation in this study * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 * Age ≥ 18 years * Use of an acceptable means of contraception for men and women of childbearing potential * International normalized ratio (INR) no greater than 1.3 and an aPTT no greater than the upper limits of normal within 28 days prior to enrollment for patients not on low-molecular-weight heparin or fondaparinux
Exclusion criteria
* Squamous cell carcinoma * Prior treatment with an investigational or marketed inhibitor of the Epidermal Growth Factor Receptor (EGFR) pathway or anti-angiogenesis agent * Systemic chemotherapy, radiotherapy, or investigational treatment within 28 days prior to randomization * Local palliative radiotherapy within 14 days prior to randomization or persistent adverse effects from radiotherapy that have not resolved to Grade 2 or less following completion of treatment * Whole brain radiotherapy or stereotactic radiosurgery for brain metastases within 4 weeks of Day 0 * Neurosurgery for brain metastases within 24 weeks of Day 0 * Brain biopsy within 12 weeks of Day 0 * Current use of dexamethasone for treatment associated with brain metastases * History of gross hemoptysis within 3 months prior to randomization unless definitively treated with surgery or radiation * History of any of the following within 6 months prior to Day 0: serious systemic disease, uncontrolled hypertension, unstable angina, New York Heart Association (NYHA) Grade 2 or greater Congestive Heart Failure (CHF), unstable symptomatic arrhythmia requiring medication, clinically significant peripheral vascular disease, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess * Evidence of bleeding diathesis or coagulopathy or other serious or acute internal bleeding within 6 months prior to randomization * Central Nervous System (CNS) bleeding; history or clinical evidence of CNS stroke (hemorrhagic or thrombotic) within the last 6 months * Progressive neurologic symptoms in patients with a history of brain metastases * Full-dose anticoagulation with warfarin * Chronic daily use of aspirin or other full-dose nonsteroidal anti-inflammatory drugs (NSAIDs) with anti-platelet activity * In-patient surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization * Minor surgical procedure, fine needle aspirations or core biopsy within 7 days prior to randomization * Anticipation of need for a major surgical procedure during the course of the study * Serious, non-healing wound, ulcer, or bone fracture * Inability to take oral medication or requirement for intravenous (IV) alimentation or total parenteral nutrition with lipids, or prior surgical procedures affecting absorption * Pregnancy or breast-feeding * Presence of another invasive cancer within 5 years prior to randomization * Evidence of confusion or disorientation, or history of major psychiatric illness that may impair the patient's understanding of the Informed Consent Form or their ability to comply with study requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) Among All Randomized Patients | From the date of randomization until the date of patient death from any cause, or the date of last contact. (Up to 3.1 years) | Overall Survival was defined as the period from the date of randomization until the date of patient death from any cause. For patients who had not died, survival data was censored at the date of last contact. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | From randomization to documented disease progression or death on study treatment, whichever occurred first. (Up to 3.1 years) | PFS was defined as the time from randomization to documented disease progression, as determined by the investigator using the Response Evaluation Criteria in Solid Tumors (RECIST), or death on study treatment, whichever occurred first. |
| Percentage of Participants With Objective Response | The median duration of Objective response was up to 9.7 months | Objective response was defined as a complete or partial response determined by RECIST on two consecutive occasions \>= 4 weeks apart. |
| Duration of Objective Response | Period from Objective response until disease progression or death on study treatment. (Up to 29.5 months) | Duration of objective response was defined as the period from the date of the initial partial or complete response until the date of disease progression or death on study treatment from any cause. For patients who had not died, data was censored at the date of last contact. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Erlotinib HCl + Bevacizumab oral erlotinib HCl 150 mg/day orally + intravenous infusion of bevacizumab at a dose of 15 mg/kg on the first day of each 3-week cycle | 319 |
| Erlotinib HCl + Placebo oral erlotinib HCl 150 mg/day orally + intravenous infusion of placebo at a dose of 15 mg/kg on the first day of each 3-week cycle | 317 |
| Total | 636 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 258 | 258 |
| Overall Study | Lost to Follow-up | 4 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Erlotinib HCl + Placebo | Total | Erlotinib HCl + Bevacizumab |
|---|---|---|---|
| Age, Continuous | 65.0 years STANDARD_DEVIATION 10.3 | 64.9 years STANDARD_DEVIATION 10.4 | 64.8 years STANDARD_DEVIATION 10.4 |
| Age, Customized >= 70 years | 108 Participants | 215 Participants | 107 Participants |
| Age, Customized Between 18 and 59 years | 90 Participants | 181 Participants | 91 Participants |
| Age, Customized Between 60 and 64 years | 66 Participants | 128 Participants | 62 Participants |
| Age, Customized Between 65 and 69 years | 53 Participants | 112 Participants | 59 Participants |
| Sex: Female, Male Female | 147 Participants | 295 Participants | 148 Participants |
| Sex: Female, Male Male | 170 Participants | 341 Participants | 171 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 258 / 313 | 258 / 313 |
| other Total, other adverse events | 310 / 313 | 306 / 313 |
| serious Total, serious adverse events | 146 / 313 | 121 / 313 |
Outcome results
Primary
Overall Survival (OS) Among All Randomized Patients
Overall Survival was defined as the period from the date of randomization until the date of patient death from any cause. For patients who had not died, survival data was censored at the date of last contact.
Time frame: From the date of randomization until the date of patient death from any cause, or the date of last contact. (Up to 3.1 years)
Population: Randomized patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib HCl + Bevacizumab | Overall Survival (OS) Among All Randomized Patients | 9.3 months |
| Erlotinib HCl + Placebo | Overall Survival (OS) Among All Randomized Patients | 9.2 months |
p-value: 0.758395% CI: [0.799, 1.177]Log Rank
Secondary
Duration of Objective Response
Duration of objective response was defined as the period from the date of the initial partial or complete response until the date of disease progression or death on study treatment from any cause. For patients who had not died, data was censored at the date of last contact.
Time frame: Period from Objective response until disease progression or death on study treatment. (Up to 29.5 months)
Population: Patients with an objective response
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib HCl + Bevacizumab | Duration of Objective Response | 9.7 months |
| Erlotinib HCl + Placebo | Duration of Objective Response | 8.4 months |
Secondary
Percentage of Participants With Objective Response
Objective response was defined as a complete or partial response determined by RECIST on two consecutive occasions \>= 4 weeks apart.
Time frame: The median duration of Objective response was up to 9.7 months
Population: Only patients with measurable disease at baseline were included in the analysis of the objective response. Patients without a post-baseline tumor assessment were considered non-responder.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib HCl + Bevacizumab | Percentage of Participants With Objective Response | 12.6 Percentage of participants |
| Erlotinib HCl + Placebo | Percentage of Participants With Objective Response | 6.2 Percentage of participants |
p-value: 0.006895% CI: [1.8, 11.3]Mantel Haenszel
Secondary
Progression-free Survival (PFS)
PFS was defined as the time from randomization to documented disease progression, as determined by the investigator using the Response Evaluation Criteria in Solid Tumors (RECIST), or death on study treatment, whichever occurred first.
Time frame: From randomization to documented disease progression or death on study treatment, whichever occurred first. (Up to 3.1 years)
Population: Randomized patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib HCl + Bevacizumab | Progression-free Survival (PFS) | 3.4 months |
| Erlotinib HCl + Placebo | Progression-free Survival (PFS) | 1.7 months |
p-value: <0.000195% CI: [0.519, 0.748]Log Rank