A Study of Herceptin (Trastuzumab) in Combination With Avastin (Bevacizumab) and Sequential Xeloda (Capecitabine) or Docetaxel in Patients With HER2-Positive Locally Recurrent or Metastatic Breast Cancer

Study Overview
=================
Brief Summary
-----------------
This single arm, open-label study will evaluate the safety and efficacy of Herceptin in combination with Avastin and sequential Xeloda in patients with locally recurrent or metastatic HER2-positive breast cancer after early relapse on adjuvant Herceptin therapy. Patients will receive Herceptin at a loading dose of 8mg/kg iv followed by 6mg/kg iv every three weeks, and Avastin 15mg/kg every 3 weeks. At first sign of disease progression Xeloda 1000mg/m2 bid po will be added on days 1-14 of each cycle, or docetaxel (100mg/m2 iv every 3 weeks) if Xeloda is not indicated for a patient. Anticipated time on study treatment is until disease-progression on second line treatment and target sample size is <100.

Official Title
-----------------
A Single Arm, Open-label Study to Evaluate the Efficacy on Tumor Response and the Safety of Bevacizumab and Trastuzumab Combination and Sequential Capecitabine in Patients With HER2 +Ive Locally Recurrent or Metastatic Breast Cancer After Early Relapse to Adjuvant Trastuzumab-containing Therapy

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Drug: bevacizumab [Avastin]
* Drug: capecitabine [Xeloda]
* Drug: docetaxel
* Drug: trastuzumab [Herceptin]


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: male or female patients, age >/=18 years locally recurrent or metastatic HER2-positive breast cancer disease progression during or up to 12 months after prior adjuvant therapy with trastuzumab LVEF >/=55% at baseline Exclusion Criteria: prior treatment with bevacizumab or capecitabine anthracyclines in prior adjuvant or neoadjuvant treatment exceeding cumulative dose of 360mg/m2 for doxorubicin and 720mg/kg for epirubicin chronic daily treatment with corticosteroids (>10mg/day methylprednisolone equivalent; excluding inhaled corticosteroids), or aspirin (>325mg/day), or clopidogrel (>75mg/day) clinically significant cardiac disease, or cardiac toxicity during previous trastuzumab therapy evidence of spinal cord compression or CNS metastasis history of other malignancy, unless disease-free for >/=5 years or treated curatively for carcinoma in situ of the cervix or non-melanomatous skin cancer

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm<br> | Drug: bevacizumab [Avastin]<br>* 15mg/kg iv every 3 weeks<br>Drug: capecitabine [Xeloda]<br>* added at time of disease-progression, 1000mg/m2 bid po days 1-14 of every 3-week cycle<br>Drug: docetaxel<br>* background therapy at time of disease progression, 100mg/m2 iv every 3 weeks<br>Drug: trastuzumab [Herceptin]<br>* 8mg/kg iv on day 1 of the first 3-week cycle, followed by 6mg/kg every 3 weeks<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival on second-line treatment |  | event-driven, tumour assessments every 6 weeks for 24 weeks, every 12 weeks thereafter | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability: AEs, laboratory parameters, LVEF |  | throughout study, laboratory parameters every 3 weeks, LVEF every 12 weeks | 
| Overall Response Rate, Best Overall Response, Duration of Response, Progression-free Survival (first-line), Overall Survival |  | event-driven, tumour assessment every 6 weeks for 24 weeks, every 12 weeks thereafter |