A Phase III, randomized, double-blind, placebo-controlled multi-center study of ASA404 in combination with paclitaxel and carboplatin as first-line treatment for locally advanced or metastatic (stage IIIb/IV) non-small cell lung cancer (NSCLC)

Lung cancer is the leading cause of cancer death in the world, affecting
approximately 171,000 people annually in the US and more than 200,000 people in
Europe. Of all these patients, approximately 85% have non-small cell lung
cancer.
Non-small cell lung cancer (NSCLC) is a heterogeneous aggregate of histologies.
The most common histologies are squamous cell carcinoma.
Patients are often diagnosed with an advanced stage of disease, and
approximately 85% of patients will die from their disease within one year with
only 1% of patients surviving 5 years.
Patients having Stage IIIb/IV NSCLC are not considered to be candidates for
curative resection surgery or radiation. Platinum and taxane based therapies
are commonly administered to patients with NSCLC, however, previous studies
indicate a response rate of only 19% and a median survival time of
approximately 8 months. Therefore, the development of new treatments is needed
for patients with NSCLC.

ASA404 is a novel Tumor-Vascular Disrupting Agent (VDA). These drugs
selectively attack tumor blood vessels, giving them broad potential against
solid cancers, which depend on their blood supply to survive and grow. ASA404
has shown synergistic qualities when combined with a carboplatin and paclitaxel
chemotherapy regimen in patients with NSCLC.

The primary objective is to compare the overall survival (OS) of patients
receiving ASA404 or placebo in combination with paclitaxel and carboplatin for
first-line treatment of stage IIIb/IV NSCLC

This is a double-blind, placebo-controlled, randomized Phase III trial.
Patients will be randomized in a 1:1 ratio into one of the following two
treatment arms:
1. ASA404 1800 mg/m2 plus paclitaxel 200mg/m2 plus carboplatin AUC 6.0 OR
2. placebo plus paclitaxel 200mg/m2 plus carboplatin AUC 6.0

Randomization will be stratified by:
* Gender (male vs. female)
* NSCLC histology (Squamous NSCLC vs. Non-Squamous NSCLC)

A total of 1200 patients will be enrolled into the study. Tumor assessments
will be performed every 6 weeks (every 2 cycles). Study treatment will be
administered for a maximum of 6 treatment cycles.

Patients will be randomized in a 1:1 ratio into one of the following two
treatment arms:

1. ASA404 1800 mg/m2 plus paclitaxel 200mg/m2 plus carboplatin AUC 6.0 OR
2. placebo plus paclitaxel 200mg/m2 plus carboplatin AUC 6.0

Patients will receive 6 cycles. Patient will have 2 visits in one cycle. On day
1 of each cycle the patient receives the studymedication will be administered
intravenously and the patient will stay in the hospital for approximately 6
hrs.
Prior to the infusion and one hour after the administration of ASA404, 6
bloodsamples will be taken (Pk and biomarkers) and 2 ECGs will be made. On day
12 of each cycle the patient returns to the hospital for a bloodtest
(hematology). Every 6 weeks a CT-scan wil be performed for tumor evaluation.
Also a bloodsample for optional biomarker study will be collected.
After discontinuation of the studymedication due to progression the patient
will be followed every 6 weeks for survival. If the patient discontinued for
other reasons than progression the patient will be followed by CT-scan every 6
weeks until progression, thereafter survival data will be collected every 6
weeks until death.

Toxicity of ASA404 in combination with paclitaxel + carboplatine or combination
with paclitaxel + carboplatine .
Radioation exposure of CT-scan and/or alleergic reaction on the contrast fluid.
The risk of taking blood may include fainting, pain, bleeding, puncture into
the vein, and/or bruising.
The risk of having an intravenous catheter includes minor infection, bleeding,
and slight discomfort or bruising at the site where the needle for the catheter
is inserted.