E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with locally advanced or metastatic Stage IIIb/IV NSCLC, of all histologies, who have progressed while on or following a first-line chemotherapy regimen and are eligible for second-line chemotherapy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066490 |
E.1.2 | Term | Progression of non small cell lung cancer |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare overall survival between the ASA404 plus docetaxel group and the placebo plus docetaxel group |
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E.2.2 | Secondary objectives of the trial |
To compare Progression-Free Survival (PFS) and the Overall Response Rate (ORR) per RECIST assessed by the investigators between patients receiving ASA404 or placebo in combination with docetaxel |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Histologically confirmed non-small cell carcinoma of the lung of all histologies. (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.Patients who have progressed while on or following a first-line chemotherapy regimen for Stage IIIb disease (malignant pleural effusion or pericardial effusion that have been confirmed cytologically) or Stage IV disease. Patients who have received bevacizumab and/or EGFR inhibitors in first-line will be eligible 3. Age ≥ 18 years old 4. WHO Performance Status of 0-2 5. Measurable or non-measurable disease per RECIST criteria (Post-text supplement 1) 6. Laboratory 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) Alkaline phosphatase ≤ 2.5 x ULN 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 ULN Electrolyte values (sodium, potassium, calcium, magnesium) within ≥1 x LLN and ≤ 1 x ULN. Patients with corrected electrolyte values are eligible Females of child-bearing potential must have negative serum pregnancy test (confirmation of negative urine pregnancy test within 72 hours prior to initial dosing) 7. Life expectancy ≥ 12 weeks 8. Written informed consent obtained according to local guidelines |
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E.4 | Principal 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 &#8804; 5 years, with the exception of non-melanoma skin cancer or cervical cancer in situ. 3. Radiotherapy &#8804; 2 weeks prior to randomization. Patients must have recovered from all radiotherapy-related toxicities. 4. Major surgery &#8804; 4 weeks prior to randomization (major surgery is defined by the use of general anesthesia). Endoscopic examinations with diagnostic intent are not considered major surgery. Minor surgery &#8804; 2 weeks prior to randomization. Insertion of a vascular access device is allowed. Insertion of a vascular access device is not considered major or minor surgery. Patients must have recovered from all surgery-related complications. 5. Treatment with first-line chemotherapy regimen &#8804; 3 weeks prior to randomization (&#8804; 6 weeks for bevacizumab, mitomycin and nitrosoureas) 6. Concurrent use of other investigational agents and patients who have received investigational agents &#8804; 4 weeks prior to randomization 7. Prior treatment with docetaxel for NSCLC in the first-line setting 8. Prior treatment with VDAs or tumor - VDAs for NSCLC in the first-line setting 9. Pleural effusion that causes &#8805; CTC grade 2 dyspnea 10. Patients with systolic BP > 160 mm Hg and/or diastolic BP > 90 mm Hg while on medication for hypertension 11. Patients with recent hemoptysis associated with NSCLC (> 1 teaspoon in a single episode within 4 weeks) 12. 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 or with implanted cardiac pacemaker 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 13. Concomitant use of drugs with a risk of causing Torsades de Pointes (See Table 6-3 and Appendix 2) 14. Known allergy or hypersensitivity to docetaxel or drugs formulated with polysorbate 80 15. Peripheral sensory neuropathy with functional impairment (CTC grade 2 neuropathy, regardless of causality) 16. 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) 17. 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.) 18. 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) 19. Significant neurologic or psychiatric disorder which could compromise participation in the study 20. Patient unwilling or unable to comply with the protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |