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

Study Overview
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Brief Summary
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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.

Official Title
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A Pilot Study of Bevacizumab Plus Carboplatin and Paclitaxel in Subjects With Advanced, Previously Untreated, Squamous Non-Small Cell Lung Cancer

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Bevacizumab
* Drug: Carboplatin
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treated with Bevacizumab<br> | Drug: Bevacizumab<br>* 15 mg/kg administered intravenously on Day 1 of each 21- to 28-day cycle, beginning on Cycle 3<br>Drug: Carboplatin<br>* Dose based on Calvert formula, on Day 1 of each 21- to 28-day cycle for a total of 6 cycles<br>Drug: Paclitaxel<br>* Dose based on patient's body surface area, on Day 1 of each 21- to 28-day cycle for a total of 6 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | First bevacizumab administration until 60 days after discontinuation of bevacizumab or death | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | First bevacizumab administration until 60 days after discontinuation of bevacizumab or death | 
| Adverse Events That Led to Discontinuation of Bevacizumab | Any treatment-emergent adverse event leading to study treatment discontinuation | First bevacizumab administration until 60 days after discontinuation of bevacizumab or death | 
| 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. | Length of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BRIDGE, NSCLC, Lung Cancer, Avastin