ATTRACT-1 Overview

ATTRACT-1 Study Title:

ATTRACT-1 Study Design:

ATTRACT-1 Primary Endpoint:

• Comparative overall survival (OS) of patients receiving ASA404 or placebo in combination with paclitaxel and carboplatin for first-line treatment of stage IIIb/IV NSCLC.

ATTRACT-1 Secondary Endpoints:

• Comparative OS of patients with squamous NSCLC receiving ASA404 or placebo in combination with paclitaxel and carboplatin.
• Comparative OS of patients with nonsquamous NSCLC receiving ASA404 or placebo in combination with paclitaxel and carboplatin.

ATTRACT-1 Key Inclusion Criteria:

• Histologically confirmed non–small cell carcinoma of the lung (Histological or cytological specimens must be collected via surgical biopsy, brushing, washing or core needle aspiration of a defined lesion. Sputum cytology is not acceptable).
• Newly diagnosed stage IIIb disease (malignant pleural effusion or pericardial effusion that has been confirmed cytologically) or stage IV disease.
• No prior systemic antineoplastic treatment for stage IIIb/IV non–small cell carcinoma of the lung (Prior neoadjuvant or adjuvant chemotherapy for earlier stage I/II NSCLC is allowed if 12 months or more prior to baseline visit).
• Age ≥18 years.
• WHO Performance Status of 0 to 1.
• Non-Small Cell Lung Cancer patients with nonmeasurable disease may still be eligible.

ATTRACT-1 Key Exclusion Criteria:

• CNS metastases (Patients having any clinical signs of CNS metastases must have a CT or MRI of the brain performed to rule out CNS metastases in order to be eligible for study participation. Patients who have had brain metastases surgically removed or irradiated with no residual disease confirmed by imaging are allowed).
• History of another primary malignancy ≤5 years, with the exception of nonmelanoma skin cancer or cervical cancer in situ.
• Radiotherapy ≤2 weeks prior to randomization. Patients must have recovered from all radiotherapy-related toxicities.
• Major surgery ≤4 weeks prior to randomization or minor surgery ≤2 weeks prior to randomization. Major surgery is defined by the use of general anesthesia, however; endoscopic examinations with diagnostic intent are not considered major surgery. Insertion of a vascular access device is exempt from this exclusion criterion. Patients must have recovered from all surgery-related complications.
• Concurrent use of other investigational agents and use of investigational agents ≤4 weeks prior to randomization.
• Prior exposure to Tumor-VDAs or other vascular targeting agents (anti-VEGF, anti-VEGF receptor agents, anti-EGFR agents [bevacizumab, cetuximab, etc]).
• Pleural effusion that causes ≥ CTC grade 2 dyspnea.
• Systolic BP >160 mm Hg and/or diastolic BP >90 mm Hg.
• Recent hemoptysis associated with NSCLC (>1 teaspoon in a single episode within 4 weeks).
• Any 1 of the following:

  Long QT syndrome.

  Baseline 12-lead ECG QTc of >450 msec per central evaluation.

  Congestive heart failure (NY Heart Association class III or IV).

  Myocardial infarction within 12 months of study entry.

  Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris.

  History of labile hypertension or poor compliance with antihypertensive regimen.

  History of a sustained ventricular tachycardia.

  Any history of ventricular fibrillation or Torsades de Pointes.

  Right bundle branch block and left anterior hemiblock (bifasicular block).

  Bradycardia defined as heart rate <50 beats per minute.

• Concomitant use of drugs with a risk of causing Torsades de Pointes.
• Known allergy or hypersensitivity to platinum-containing drugs, taxanes, other drugs formulated in Cremophor EL (polyoxyethylated castor oil) or any known excipients of these drugs.
• Peripheral sensory neuropathy with functional impairment (CTC grade 2 neuropathy, regardless of causality).
• Concurrent severe and/or uncontrolled medical disease (eg, uncontrolled diabetes, chronic renal disease, chronic liver disease, confirmed diagnosis of HIV infection or active uncontrolled infection).
• Significant neurologic or psychiatric disorder that could compromise participation in the study.