Non-small Cell Lung Cancer
Conditions
Keywords
BRIDGE, NSCLC, Lung Cancer, Avastin
Brief summary
This is an open-label, single-arm, multicenter pilot study to evaluate the safety and efficacy of carboplatin/paclitaxel+bevacizumab in subjects with locally advanced (Stage IIIb with pleural effusion/pericardial effusion), Stage IV, or recurrent squamous Non-Small Cell Lung Cancer (NSCLC) who have not received prior systemic therapy for metastatic disease.
Interventions
DRUGBevacizumab
15 mg/kg administered intravenously on Day 1 of each 21- to 28-day cycle, beginning on Cycle 3
DRUGCarboplatin
Dose based on Calvert formula, on Day 1 of each 21- to 28-day cycle for a total of 6 cycles
DRUGPaclitaxel
Dose based on patient's body surface area, on Day 1 of each 21- to 28-day cycle for a total of 6 cycles
Sponsors
Genentech, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed Informed Consent Form(s) * At least 18 years of age * Advanced histologically or cytologically confirmed predominant squamous NSCLC * Subjects with treated brain metastases are eligible if there is no evidence of progression or hemorrhage after treatment of the brain metastasis/metastases * Prior treatment for CNS disease as deemed appropriate by the treating physician * ECOG performance status 0, 1, or 2 * Measurable or evaluable disease * Use of an accepted and effective method of contraception (hormonal or barrier methods, abstinence) prior to study entry and for the duration of the study (for women of childbearing potential and sexually active men)
Exclusion criteria
* Prior chemotherapy for metastatic disease * Adjuvant chemotherapy or prior combined modality therapy (chemotherapy plus radiotherapy) if \< 6 months has elapsed from completion of treatment to Day 1, Cycle 1 * Extrathoracic metastases as the only sites of disease * Active malignancy other than lung cancer * Current, recent, or planned participation in another experimental drug study * Untreated brain metastases * Presence of intrathoracic lesion(s) with any cavitation * Gross hemoptysis within 3 months prior to Day 1 * In the opinion of the investigator or local radiologist, evidence of tumor that is extending into the lumen of a major blood vessel * Inadequately controlled hypertension * Unstable angina or NYHA Grade II or greater CHF * Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1 * Myocardial infarction within 6 months prior to Day 1, Cycle 1 * Stroke within 6 months prior to Day 1, Cycle 1 * Active symptomatic peripheral vascular disease within 6 months prior to Day 1, Cycle 1 * History of significant vascular disease * Evidence of bleeding diathesis or coagulopathy * Current, ongoing treatment with full-dose warfarin or its equivalent * Current or recent use of aspirin (\>325 mg/day) * Known hypersensitivity to any components of bevacizumab * Serious, non-healing wound, ulcer, or bone fracture * UPC ratio ≥ 1.0 * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, Cycle 1, or anticipation of need for major surgical procedure during the course of the study * Pregnancy or lactation * Inadequate organ function * Any other medical conditions (including mental illness or substance abuse) deemed by the clinician to be likely to interfere with a subject's ability to provide informed consent, cooperate, or participate in the study, or to interfere with the interpretation of the results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Grade ≥3 Pulmonary Hemorrhage Adverse Events | First bevacizumab administration until 60 days after discontinuation of bevacizumab or death | To estimate the rate of National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE), Version 3.0, Grade ≥3 pulmonary hemorrhage adverse events. Per NCI CTCAE v.3: Grade 3 = Transfusion, interventional radiology, endoscopic, or operative intervention indicated; radiation therapy (i.e., hemostasis of bleeding site); Grade 4 = Life-threatening consequences; major urgent intervention indicated; Grade 5 = Death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Selected Adverse Events | First bevacizumab administration until 60 days after discontinuation of bevacizumab or death | Selected treatment-emergent adverse events for any grade of pulmonary hemorrhage, any grade of non-pulmonary hemorrhage, any grade of gastrointestinal perforation, Grade ≥ 2 arterial thromboembolic events, Grade ≥ 2 left ventricular systolic dysfunction, Grade ≥ 3 proteinuria, and Grade ≥ 3 hypertension. Refer to NCI CTCAE v.3 for grading definitions. Serious adverse events (SAEs) occurring in any of the above categories are included. See the Serious Adverse Events section below for full SAE reporting. |
| Adverse Events That Led to Discontinuation of Bevacizumab | First bevacizumab administration until 60 days after discontinuation of bevacizumab or death | Any treatment-emergent adverse event leading to study treatment discontinuation |
| Progression-free Survival | Length of study | Progression-free survival (PFS) was defined as the time from enrollment to the time of documented disease progression or death from any cause, whichever occurred earlier. PFS was determined for only those patients that received bevacizumab. Summary of PFS (median) was estimated from Kaplan-Meier curve. The 95% confidence interval (CI) for the median was computed using the method of Brookmeyer and Crowley. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treated With Bevacizumab Chemotherapy (carboplatin + paclitaxel) in combination with bevacizumab in intervals of chemotherapy alone (Cycles 1 and 2), chemotherapy + bevacizumab (Cycles 3-6), and bevacizumab alone (Cycles 7 and beyond). | 31 |
| Total | 31 |
Baseline characteristics
| Characteristic | Treated With Bevacizumab |
|---|---|
| Age Continuous | 65.0 years STANDARD_DEVIATION 7.9 |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 12 / 31 |
| serious Total, serious adverse events | 18 / 31 |
Outcome results
Primary
Incidence of Grade ≥3 Pulmonary Hemorrhage Adverse Events
To estimate the rate of National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE), Version 3.0, Grade ≥3 pulmonary hemorrhage adverse events. Per NCI CTCAE v.3: Grade 3 = Transfusion, interventional radiology, endoscopic, or operative intervention indicated; radiation therapy (i.e., hemostasis of bleeding site); Grade 4 = Life-threatening consequences; major urgent intervention indicated; Grade 5 = Death.
Time frame: First bevacizumab administration until 60 days after discontinuation of bevacizumab or death
Population: Safety-evaluable patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treated With Bevacizumab | Incidence of Grade ≥3 Pulmonary Hemorrhage Adverse Events | 3.2 Percentage of patients |
90% CI: [0.3, 13.5]Blyth-Still-Casella
Secondary
Adverse Events That Led to Discontinuation of Bevacizumab
Any treatment-emergent adverse event leading to study treatment discontinuation
Time frame: First bevacizumab administration until 60 days after discontinuation of bevacizumab or death
Population: Safety-evaluable patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treated With Bevacizumab | Adverse Events That Led to Discontinuation of Bevacizumab | Pulmonary Embolism | 1 Patients |
| Treated With Bevacizumab | Adverse Events That Led to Discontinuation of Bevacizumab | Cerebral Infarction | 1 Patients |
| Treated With Bevacizumab | Adverse Events That Led to Discontinuation of Bevacizumab | Cerebral Ischemia | 1 Patients |
| Treated With Bevacizumab | Adverse Events That Led to Discontinuation of Bevacizumab | Neuropathy Peripheral | 1 Patients |
| Treated With Bevacizumab | Adverse Events That Led to Discontinuation of Bevacizumab | Deep Vein Thrombosis | 2 Patients |
| Treated With Bevacizumab | Adverse Events That Led to Discontinuation of Bevacizumab | Hypertension | 1 Patients |
| Treated With Bevacizumab | Adverse Events That Led to Discontinuation of Bevacizumab | Dyspnea | 1 Patients |
| Treated With Bevacizumab | Adverse Events That Led to Discontinuation of Bevacizumab | Cardiac Failure Congestive | 1 Patients |
| Treated With Bevacizumab | Adverse Events That Led to Discontinuation of Bevacizumab | Proteinuria | 1 Patients |
Secondary
Progression-free Survival
Progression-free survival (PFS) was defined as the time from enrollment to the time of documented disease progression or death from any cause, whichever occurred earlier. PFS was determined for only those patients that received bevacizumab. Summary of PFS (median) was estimated from Kaplan-Meier curve. The 95% confidence interval (CI) for the median was computed using the method of Brookmeyer and Crowley.
Time frame: Length of study
Population: Enrolled patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treated With Bevacizumab | Progression-free Survival | 6.2 Months |
Secondary
Selected Adverse Events
Selected treatment-emergent adverse events for any grade of pulmonary hemorrhage, any grade of non-pulmonary hemorrhage, any grade of gastrointestinal perforation, Grade ≥ 2 arterial thromboembolic events, Grade ≥ 2 left ventricular systolic dysfunction, Grade ≥ 3 proteinuria, and Grade ≥ 3 hypertension. Refer to NCI CTCAE v.3 for grading definitions. Serious adverse events (SAEs) occurring in any of the above categories are included. See the Serious Adverse Events section below for full SAE reporting.
Time frame: First bevacizumab administration until 60 days after discontinuation of bevacizumab or death
Population: Safety-evaluable patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treated With Bevacizumab | Selected Adverse Events | Any grade of pulmonary hemorrhage | 2 Patients |
| Treated With Bevacizumab | Selected Adverse Events | Any grade of non-pulmonary hemorrhage | 0 Patients |
| Treated With Bevacizumab | Selected Adverse Events | Any grade of gastrointestinal perforation | 0 Patients |
| Treated With Bevacizumab | Selected Adverse Events | Grade ≥ 2 arterial thromboembolic events | 2 Patients |
| Treated With Bevacizumab | Selected Adverse Events | Grade ≥ 2 left ventricular systolic dysfunction | 1 Patients |
| Treated With Bevacizumab | Selected Adverse Events | Grade ≥ 3 proteinuria | 1 Patients |
| Treated With Bevacizumab | Selected Adverse Events | Grade ≥ 3 hypertension | 5 Patients |