Trial of Ombrabulin (AVE8062) in Combination With Taxane and Platinum in Patients With Non-small Cell Lung Cancer

A Multinational, Randomized, Double Blind, Controlled Phase II Trial of Ombrabulin With Taxane and Platinum Combination Administered Every Three Weeks, in First Line Treatment of Patients Metastatic Non-small Cell Lung Cancer

Primary Objective:

• To demonstrate progression free survival (PFS) improvement for ombrabulin compared to placebo, in combination with taxane and platinum, as first line treatment for patients with metastatic non-small cell lung cancer (NSCLC).

Secondary Objective:

• To determine overall survival (OS), overall response rate (ORR) according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria, safety, and evaluate potential biomarkers, pharmacokinetic (PK) analysis of ombrabulin and its main metabolite, RPR258063, using a population approach.

Patients will be treated for a maximum of 6 cycles (21 days each), in the absence of unacceptable toxicity or disease progression or consent withdrawal. All patients will be followed for disease progression documentation and for patient status until up to one year after the primary analysis cutoff date.

Inclusion criteria:

• Histologically proven squamous metastatic non-small cell lung cancer (stage IV, according to Tumor Nodes Metastasis (TNM) classification seventh edition)
• Patients with measurable disease, Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

Exclusion criteria:

• Prior chemotherapy, immunotherapy or targeted therapy for lung cancer disease (including adjuvant/neoadjuvant therapy)
• History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis
• History of another neoplasm. Adequately treated basal cell or squamous skin cancer, or in situ cervical cancer, or any other cancer from which the patient has been disease-free for >5 years are allowed
• Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to randomization
• Acquired immunodeficiency syndrome (AIDS-related illness) or known human immunodeficiency virus (HIV) disease requiring antiretroviral treatment
• Any severe acute or chronic medical condition, which could impair the ability of the patient to participate in the study or interfere with interpretation of study results
• Pregnant or breast-feeding woman. Positive serum or urine pregnancy test prior to randomization
• Patient with reproductive potential (Male/Female) who do not agree to use accepted and effective method of contraception during the study treatment period and for at least 3 months after the completion of the study treatment. The definition of "effective method of contraception" will be based on the investigator's judgment
• Inadequate organ function
• Pre-existing peripheral neuropathy > grade 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V.4.03
• Pre-existing hearing impairment > grade 2
• Known hypersensitivity due to taxanes and /or polysorbate 80 or any other compound of the study drug combination
• Other serious illness or medical conditions such as (but not restricted): Active infection, Superior vena cava syndrome, Pericardial effusion requiring intervention (drainage)
• Documented medical history of myocardial infarction, documented angina pectoris, arrhythmia especially severe conduction disorder such as second or third-degree atrioventricular block, stroke, or history of arterial or venous thromboembolism within the past 6 months still requiring anticoagulants.
• Uncontrolled hypertension within 3 months prior to study treatment or patient with organ damage related to hypertension.
• Patient with Left Ventricular Ejection Fraction (LVEF) value lower than institution inferior normal limit, evaluated by echocardiography or angiocardiography
• 12-lead Electrocardiogram (ECG): Infarction Q-wave, ST segment depression or elevation ≥1 mm in at least 2 contiguous leads
• History of gross hemoptysis (i.e. 1/2 teaspoon of red blood or more per episode) within the past 1 month.
• Has non-squamous NSCLC(adenocarcinoma/large cell or other)

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.