Clinical trial NCT00662597 (phase 3, status: terminated)
Conditions: non-small cell lung cancer
ICD codes: C78.00, C78.01, C78.02, D14.30, D14.31, D14.32, C34.2
Drugs: asa404, placebo, carboplatin, paclitaxel
SMILES: CC1=C(C)C2=C(C=C1)C(=O)C1=CC=CC(CC(O)=O)=C1O2, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, N[C@@H](CCCNC(N)=N)C(O)=O, [H][C@@]1(C[C@@H](C)[C@]2([H])CC(=O)[C@H](C)\C=C(C)\[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\C=C\C=C\C=C(C)\[C@H](C[C@]3([H])CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O2)OC)CC[C@@H](OCCO)[C@@H](C1)OC
Eligibility 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 supplement 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) ≤ 1.5 x IULN
                  (Sections 6.9.1 and 7.3.4.2)

               -  Electrolyte values (potassium, calcium, magnesium) within > 1 x LLN and < 1 x
                  ULN. Patients with corrected electrolyte values are eligible. See Sections 6.8.1
                  and 7.3.4.3.

               -  Females of child-bearing potential must have negative serum pregnancy test
                  (confirmation of negative urine pregnancy test within 72 hours prior to initial
                  dosing).

          8. Life expectancy ≥ 12 weeks

          9. Written informed consent obtained according to local guidelines

        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 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 < 50 beats per minute

         11. Concomitant use of drugs with a risk of causing Torsades de Pointes (See Table 6-3)

         12. 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.

         13. Peripheral sensory neuropathy with functional impairment (CTC grade 2 neuropathy,
             regardless of causality)

         14. Pregnant or breast feeding females

             • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
             female after conception and until the termination of gestation, confirmed by a
             positive hCG laboratory test (> 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. (Adequate forms of contraception include IUD, oral or depot contraceptive
             or the barrier method plus spermicide.)

             • Oral, implantable, or injectable contraceptives may be affected by cytochrome P450
             interactions while taking paclitaxel and therefore are not considered effective
             contraceptive methods for this study when used as a single agent. Therefore, it is
             highly recommended that a concomitant barrier method be used with oral, implantable,
             or injectable contraceptives. The investigator shall counsel the patient accordingly.
             Women of childbearing potential must have a negative pregnancy test (serum or urine)
             72 hours prior to administration of study treatment. For a list of substrates of human
             liver microsomal P450 enzymes, visit website (http://medicine.iupui.edu/flockhart/)

         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 compromise participation in
             the study Patient unwilling or unable to comply with the protocol

        Other protocol-defined inclusion/exclusion criteria may apply