Study Evaluating the Safety and Efficacy of MEGF0444A in Combination With Carboplatin, Paclitaxel and Bevacizumab in Patients With Advanced or Recurrent Non-Squamous Non-Small Cell Lung Cancer Who Have Not Received Prior Chemotherapy for Advanced Disease (NILE)

Study Overview
=================
Brief Summary
-----------------
This is a Phase II, multicenter, randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of MEGF0444A combined with paclitaxel + carboplatin + bevacizumab therapy in patients with histologically or cytologically documented inoperable, locally advanced, metastatic (Stage IV), or recurrent non-squamous NSCLC.

Official Title
-----------------
A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of MEGF0444A in Combination With Carboplatin , Paclitaxel and Bevacizumab in Patients With Advanced or Recurrent Non-Squamous Non-Small Cell Lung Cancer Who Have Not Received Prior Chemotherapy for Advanced Disease

Conditions
-----------------
Non-Squamous Non-Small Cell Lung Cancer

Intervention / Treatment
-----------------
* Drug: MEGF0444A
* Drug: bevacizumab
* Drug: carboplatin
* Drug: paclitaxel
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically documented inoperable (Stage IV) or recurrent non-squamous non-small cell lung cancer (NSCLC). Diagnoses of non-squamous NSCLC that are based on sputum cytology alone are not acceptable. Mixed tumors should be categorized according to the predominant cell type. ECOG performance status of 0 or 1 Life expectancy >12 weeks Measurable disease, as defined by RECIST 1.1 Adequate hematologic and end organ function Exclusion Criteria: Prior therapy (including chemotherapy, antibody therapy, tyrosine kinase inhibitors,radiotherapy, immunotherapy, hormonal therapy or investigational therapy) before Day 1 of Cycle 1 for the treatment of Stage IV or recurrent NSCLC. Patients who received prior adjuvant chemotherapy or radiotherapy for NSCLC are not excluded if the time interval from completion of adjuvant therapy until disease progression is > 12 months. Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment Malignancies other than NSCLC within 5 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent Pregnant and lactating women Active infection requiring IV antibiotics Bevacizumab-Specific Exclusions: Histologically or cytologically documented inoperable, locally advanced, mixed non-small cell and small cell tumors or mixed adenosquamous carcinomas with a predominant squamous component Evidence of tumor invading major blood vessels on imaging Evidence of central nervous system (CNS) metastases History of stroke or transient ischemic attacks (TIAs) within 6 months prior to Day 1 Significant vascular disease within 6 months prior to Day 1 Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: MEGF0444A<br>* Intravenous repeating dose<br>Drug: bevacizumab<br>* Intravenous repeating dose<br>Drug: carboplatin<br>* Intravenous repeating dose<br>Drug: paclitaxel<br>* Intravenous repeating dose<br>|
| Experimental: B<br> | Drug: bevacizumab<br>* Intravenous repeating dose<br>Drug: carboplatin<br>* Intravenous repeating dose<br>Drug: paclitaxel<br>* Intravenous repeating dose<br>Drug: placebo<br>* Intravenous repeating dose<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (defined as the time from randomization to the first occurrence of progression based on RECIST 1.1 criteria or death from any cause on study) |  | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response (partial response plus complete response) as determined by the Investigator using RECIST 1.1 |  | Up to 24 months | 
| Duration of objective response (defined as the first occurrence of a documented objective response until the time of progression or death from any cause on study) |  | Up to 24 months | 
| Overall survival (defined as the time from randomization until death from any cause) |  | Up to 24 months |