A Study of AMG 706 or Bevacizumab, in Combination With Paclitaxel Chemotherapy, as Treatment for Breast Cancer

Study Overview
=================
Brief Summary
-----------------
To determine if treatment with paclitaxel plus AMG 706 is superior to paclitaxel plus AMG 706 placebo in subjects with HER2 negative locally recurrent or metastatic breast cancer. Also to estimate differences between treatment with paclitaxel plus AMG 706 and paclitaxel plus bevacizumab.

Official Title
-----------------
A Randomized Phase 2 Trial of Double-Blind, Placebo Controlled AMG 706 in Combination With Paclitaxel, or Open-Label Bevacizumab in Combination With Paclitaxel, as First Line Therapy in Women With HER2 Negative Locally Recurrent or Metastatic Breast Cancer

Conditions
-----------------
Breast Neoplasms, Breast Tumors, Breast Cancer, Locally Recurrent and Metastatic Breast Cancer

Intervention / Treatment
-----------------
* Drug: AMG 706 placebo
* Drug: Bevacizumab
* Drug: AMG 706
* Drug: Paclitaxel


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease. Measurable disease by RECIST guidelines. Tumor (primary or metastatic) must be HER2 negative. Adequate organ and hematologic function. Exclusion: Taxane treatment within 12 months prior to registration. Prior chemotherapy for locally recurrent or metastatic breast cancer (prior endocrine therapy is permitted). Prior radiation therapy, radiofrequency ablation, percutaneous cryotherapy or hepatic chemoembolization on all sites of measurable disease. Current or prior history of central nervous system metastases. Peripheral neuropathy ≥ grade 2 (CTCAE v3.0) at registration. History of arterial or venous thrombosis within 1 year prior to registration. History of bleeding diathesis or bleeding within 14 days of registration. Uncontrolled hypertension (systolic >145 mmHg; diastolic >85 mmHg). Clinically significant cardiac disease within 12 months of registration. Known HIV positive, hepatitis C positive or hepatitis B surface antigen positive. Prior treatment with VEGFr targeted therapies.

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

Sexes Eligible for Study
-----------------
Female

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Arm A Placebo<br>Blinded AMG 706 placebo plus paclitaxel | Drug: AMG 706 placebo<br>* Blinded placebo<br>Drug: Paclitaxel<br>* Paclitaxel is an antineoplastic agent that acts by promoting and stabilizing the polymerization of microtubules.<br>|
| Experimental: Arm B Experimental<br>Blinded AMG 706 plus paclitaxel | Drug: AMG 706<br>* AMG 706 is a small organic molecule that has been shown in preclinical pharmacology and PK studies to be a potent, oral, multi-kinase inhibitor with anti-angiogenic and anti-tumor activity achieved by selectively targeting all known VEGF, PDGF and Kit receptors.<br>* Other names: motesanib diphosphate;Drug: Paclitaxel<br>* Paclitaxel is an antineoplastic agent that acts by promoting and stabilizing the polymerization of microtubules.<br>|
| Active Comparator: Arm C Comparator<br>Open-label bevacizumab plus paclitaxel | Drug: Bevacizumab<br>* Bevacizumab is a recombinant, humanized anti-VEGF monoclonal antibody.<br>* Other names: Avastin;Drug: Paclitaxel<br>* Paclitaxel is an antineoplastic agent that acts by promoting and stabilizing the polymerization of microtubules.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate, measured radiologically and assessed by an independent review committee. |  | Last patient enrolled + 16 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival, duration of response, clinical benefit rate (percentage of subjects with complete response, partial response or stable disease lasting >24 weeks), overall survival and incidence of adverse events. |  | >24 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
AMG 706, Paclitaxel, Metastatic Breast Cancer, Antiangiogenic, Bevacizumab