This phase III trials is conducted world-wide in order to demonstrate safety and efficacy of ASA404 in combination with a paclitaxel-carboplatin chemotherapy in the treatment of patients with stage IIIb/IV NSCLC who are eligible for a first line chemotherapy. The study population will consist of patients with NSCLC of all histologies eligible for first-line therapy. MedDRA version: 9.1 Level: LLT Classification code 10066490 Term: Progression of non small cell lung cancer
Conditions
Interventions
Product Code: ASA404
Pharmaceutical Form: Concentrate for solution for infusion
Current Sponsor code: ASA404
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration n
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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.) 2. Newly diagnosed Stage IIIb disease (malignant pleural effusion or pericardial effusion that have been confirmed cytologically) or Stage IV disease 3. 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) 4. Age = 18 years old 5. WHO Performance Status of 0-1 6. Measurable or non-measurable disease per RECIST criteria (Post-text suppl 1) 7. Lab values within the range, as defined below, within 2 weeks of randomization: • Absolute neutrophils count (ANC) > 2.0 x 109/L • Platelets = 100 x109/L • Hemoglobin = 10 g/dL • Serum creatinine = 1.5 x ULN (= 120 micro mol/L) • Serum bilirubin = 1.5 x ULN (= 25 micro mol/L) • Aspartate transaminase (AST) and alanine transaminase (ALT) = 2.5 x ULN (= 5 x ULN if liver metastases) • International Normalized Ratio (INR) or Prothrombin Time (PT) 1 x LLN and =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients having 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.). 2. Patients with a history of another primary malignancy = 5 years, with the exception of non-melanoma skin cancer or cervical cancer in situ. 3. Radiotherapy = 2 weeks prior to randomization. Patients must have recovered from all radiotherapy-related toxicities. 4. Major surgery = 4 weeks prior to randomization (major surgery is defined by the use of general anesthesia). Minor surgery = 2 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 criteria. Patients must have recovered from all surgery-related complications. 5. Concurrent use of other investigational agents and patients who have received investigational agents = 4 weeks prior to randomization 6. Prior exposure to Tumor-VDAs or other vascular targeting agents (anti-VEGF, anti-VEGF receptor agents, anti-EGFR agents [bevacizumab, cetuximab, etc.]) 7. Pleural effusion that causes = CTC grade 2 dyspnea 8. Patients with systolic BP > 160 mm Hg and/or diastolic BP >90 mm Hg 9. Patients with recent hemoptysis associated with NSCLC (>1 teaspoon in a single episode within 4 weeks) 10. Patients with any one of the following: • Patients with long QT syndrome • Patients with a Baseline 12-lead ECG QTc of >450 msec per central evaluation • Congestive heart failure (NY Heart Association class III or IV) • Patients with a 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 anti-hypertensive 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 5 mIU/ml) 15. Women of child bearing potential or sexually active males, unwilling or unable to use the required highly effective method(s) of contraception for both sexes while receiving treatment and for at least 6 months after the discontinuation of study treatment. 16. Concurrent severe and/or uncontrolled medical disease (i.e. uncontrolled diabetes, chronic renal disease, chronic liver disease, confirmed diagnosis of HIV infection or active uncontrolled infection). 17. Significant neurologic or psychiatric disorder which could com
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: - To compare the OS of patients with non-squamous NSCLC receiving ASA404 or placebo in combination with paclitaxel and carboplatin - To compare the OS of patients with squamous NSCLC receiving ASA404 or placebo in combination with paclitaxel and carboplatin;Primary end point(s): Overall survival (OS) - time from the date of randomization to the date of death due to any cause, or the last date the patient was known to be alive (censored observation) at the date of the data cutoff for the final analysis. | — |
Countries
Belgium, Czech Republic, France, Germany, Greece, Hungary, Italy, Netherlands, Poland, Spain, Sweden, United Kingdom
Outcome results
None listed