A Study of Bevacizumab Plus Carboplatin and Paclitaxel in Subjects With Advanced, Previously Untreated, Squamous Non-Small Cell Lung Cancer (BRIDGE)

Phase 2

Completed

Conditions: Non-small Cell Lung Cancer

Interventions: Drug: Bevacizumab
Drug: Carboplatin
Drug: Paclitaxel

Registration Number: NCT00318136

Lead Sponsor: Genentech, Inc.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 47

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treated with Bevacizumab	Bevacizumab	-
Treated with Bevacizumab	Carboplatin	-
Treated with Bevacizumab	Paclitaxel	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.