A phase III, randomized, double-blind, placebo-controlled multi-center study of ASA404 in combination with docetaxel in second-line treatment of patients with advanced or metastatic (stage IIIb/IV) non-small cell lung cancer (NSCLC). - ATTRACT-2

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-002309-38-NL
• Date of registration: 26/02/2010
• Prospective Registration: No
• Primary sponsor: Novartis Pharma Services AG
• Public title: A phase III, randomized, double-blind, placebo-controlled multi-center study of ASA404 in combination with docetaxel in second-line treatment of patients with advanced or metastatic (stage IIIb/IV) non-small cell lung cancer (NSCLC). - ATTRACT-2
• Scientific title: A phase III, randomized, double-blind, placebo-controlled multi-center study of ASA404 in combination with docetaxel in second-line treatment of patients with advanced or metastatic (stage IIIb/IV) non-small cell lung cancer (NSCLC). - ATTRACT-2
• Date of first enrolment: 09/04/2009
• Target sample size: 900
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-002309-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Belgium, Germany, Hungary, Italy, Netherlands, Poland, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Histologically confirmed non-small cell carcinoma of the lung of all histologies.
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. Not applicable per amendment 2
6. Central or local 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
• Serum bilirubin = 1.5 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). Any female presenting with a positive or borderline pregnancy test must undergo a gynecological exam and ultrasound to rule out pregnancy and if found to be negative may be included in the trial.
7. Life expectancy = 12 weeks
8. Written informed consent obtained according to local guidelines
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Patients having CNS metastases
2. Patients with a concurrent malignancy, or history of prior malignancy within the past three years, except for basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, treated early stage (T1a) prostate cancer or treated early stage (DCIS or LCIS) breast cancer.
3. Radiotherapy = 2 weeks prior to randomization. Patients must have recovered from all acute radiotherapy-related toxicities.
4. Major surgery must be completed 4 weeks prior to starting study treatment. Major surgery is defined at the investigator’s discretion. Insertion of a vascular access device is not considered major or minor surgery. Patients must have recovered from all acute surgery-related complications.
5. Treatment with all prior anticancer therapies = 3 weeks prior to randomization (= 6 weeks for bevacizumab, mitomycin and nitrosoureas)
6. Concurrent use of other investigational agents and patients who have received investigational agents = 4 weeks prior to randomization
7. Prior treatment with docetaxel for NSCLC in the locally advanced or metastatic first-line setting
8. Prior treatment with VDAs or tumor - VDAs
9. Any medical condition resulting in = 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 QTcF of > 450 msec for men or >470 msec for women using the Fridericia [QTcF formula] measurement determined per central ECG
evaluation
• Congestive heart failure (NY Heart Association class III or IV)
• Patients with a myocardial infarction within 12 months of starting study treatment or with implanted cardiac pacemaker
• Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris
• History of poorly-controlled hypertension or poor compliance with antihypertensive regimen
• History of a sustained ventricular tachycardia
• Presence of atrial tachyarrhythmia (e.g., atrial fibrillation, atrial flutter, multifocal trial tachycardia, supraventricular tachycardia) if not effectively rate-controlled
• History of ventricular fibrillation or Torsades de Pointes (TdP)
• Right bundle branch block (RBBB) and either left anterior hemiblock or left posterior hemiblock (bifasicular block)
• Bradycardia defined as heart rate < 50 beats per minute
• Any clinically significant cardiac abnormality as assessed by the investigator
13. Patients who are currently receiving treatment with any medications that have the potential to prolong QT interval or are known to have a risk of causing Torsades de Pointes which cannot be either safely discontinued or switched to a different medication prior to starting study drug administration must be discussed with and reviewed by the Novartis Global Clinical team prior to randomization.
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
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 stu

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with 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 line chemotherapy
MedDRA version: 9.1 Level: LLT Classification code 10066490 Term: Progression of non small cell lung cancer

Intervention(s)

Product Name: vadimezan
Product Code: ASA404
Pharmaceutical Form: Concentrate for solution for infusion
CAS Number: 29095-08-5
Current Sponsor code: ASA404
Other descriptive name: 5,6-Dimethylxanthenone-4-acetic acid
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 180-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: Taxotere
Product Name: Docetaxel
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: DOCETAXEL
CAS Number: 114977-28-5
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 40-

Primary Outcome(s)

Main Objective: To compare overall survival between the ASA404 plus docetaxel group and the placebo plus docetaxel group

Primary end point(s): The primary efficacy endpoint will be overall survival

Secondary Objective: 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

Secondary ID(s)

N/A

2008-002309-38-ES

CASA404A2302