A Study of ASA404 or Placebo in Combination With Docetaxel in Second-line Treatment for (Stage IIIb/IV) Non-small Cell Lung Cancer (ATTRACT-2)

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00738387
First received: August 19, 2008
Last updated: May 2, 2012
Last verified: May 2012
  Purpose

The purpose of this study is to determine if adding ASA404 to docetaxel chemotherapy makes the cancer treatment more effective in patients with locally advanced or metastatic non-small cell lung cancer


Condition Intervention Phase
Non-Small Cell Lung Cancer
Drug: ASA404
Drug: Placebo
Drug: docetaxel
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official 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 Locally Advanced or Metastatic (Stage IIIb/IV) Non-small Cell Lung Cancer (NSCLC)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Overall survival [ Time Frame: Every 6 weeks from study treatment discontinuation until death or loss to follow-up ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression free survival [ Time Frame: Every 6 weeks from study treatment discontinuation until documented PD, death or loss to follow-up ] [ Designated as safety issue: No ]
  • Overall response rate [ Time Frame: Every 42 days (=/- 7 days) from date of randomization until PD ] [ Designated as safety issue: No ]
  • Quality of life [ Time Frame: At every odd cycle and at end of treatment ] [ Designated as safety issue: No ]
  • Biomarker assessments [ Time Frame: 1 hr post-study drug at cycles 1, 2, 4, 6 and End of Treatment ] [ Designated as safety issue: No ]
  • Pharmacokinetic assessments [ Time Frame: 1 hr post-study drug, optional 3-5 hr post-study drug at cycles 1, 2, 3, 4, 5 and 6 ] [ Designated as safety issue: No ]

Enrollment: 900
Study Start Date: December 2008
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ASA404 + docetaxel

1800 mg/m2 of ASA404 intravenous (IV) on day 1 of each 21 day cycle

75 mg/m2 of docetaxel intravenous (IV) an hour for 1st 6 cycles; cycle: every 21 days

Drug: ASA404
1800 mg/m2 of ASA404 i.v. on day 1 of each 21 day cycle
Drug: docetaxel
75 mg/m2 of docetaxel intravenous (IV) an hour for 1st 6 cycles; cycle: every 21 days
Placebo Comparator: Placebo + docetaxel

Placebo i.v. on day 1 of each 21 day cycle

75 mg/m2 of docetaxel intravenous (IV) an hour for 1st 6 cycles; cycle: every 21 days

Drug: Placebo
Placebo i.v. on day 1 of each 21 day cycle
Drug: docetaxel
75 mg/m2 of docetaxel intravenous (IV) an hour for 1st 6 cycles; cycle: every 21 days

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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. Not applicable per amendment#2
  6. Central 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 may undergo a gynecological exam and ultra sound 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

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 concurrent malignancy, or history or prior malignancy within the past two 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 report
    • 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 anti-hypertensive regimen
    • History of a sustained ventricular tachycardia
    • Presence of atrial tachycardia (e.g., atrial fibrillation, atrial flutter, multifocal atrial 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
    • [For China only: Patients older than 70 years with evidence of myocardial ischemia by coronary artery angiography or cardiac radionucleotide imaging examination]
    • [For China only: Patients with LVEF <=40%]
    • 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 (See Section 6.8.5.1 and Appendix 2) which cannot be either safely discontinued or switched to a different medication prior to starting study drug administration must be discussed with and approved 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

    • 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.)

    • Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions while taking docetaxel 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/)

  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
  21. Patients receiving full-dose therapeutic oral or parenteral anticoagulation are ineligible. Patients receiving thrombolytic therapy within 10 days of starting are also ineligible.

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00738387

  Show 163 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00738387     History of Changes
Other Study ID Numbers: CASA404A2302, EUDRACT number: 2008-002309-38
Study First Received: August 19, 2008
Last Updated: May 2, 2012
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Argentina: Human Research Bioethics Committee
Argentina: Ministry of Health
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Belgium: Federal Agency for Medicinal Products and Health Products
Belgium: Institutional Review Board
Belgium: Ministry of Social Affairs, Public Health and the Environment
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
Brazil: Ethics Committee
Brazil: Ministry of Health
Brazil: National Committee of Ethics in Research
Brazil: National Health Surveillance Agency
Canada: Ethics Review Committee
Canada: Health Canada
Canada: Ministry of Health & Long Term Care, Ontario
China: Ethics Committee
China: Ministry of Health
China: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Direction Générale de la Santé
France: French Data Protection Authority
France: Haute Autorité de Santé Transparency Commission
France: Institutional Ethical Committee
France: Ministry of Health
France: National Consultative Ethics Committee for Health and Life Sciences
Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
Germany: Federal Ministry of Education and Research
Germany: Federal Ministry of Food, Agriculture and Consumer Protection
Germany: German Institute of Medical Documentation and Information
Germany: Ministry of Health
Germany: Paul-Ehrlich-Institut
Hungary: National Institute of Pharmacy
Israel: The Israel National Institute for Health Policy Research and Health Services Research
Israel: Ethics Commission
Israel: Israeli Health Ministry Pharmaceutical Administration
Israel: Ministry of Health
Italy: Ethics Committee
Italy: Ministry of Health
Italy: National Bioethics Committee
Italy: National Institute of Health
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Italy: The Italian Medicines Agency
Japan: Foundation for Biomedical Research and Innovation
Japan: Institutional Review Board
Japan: Ministry of Education, Culture, Sports, Science and Technology
Japan: Ministry of Health, Labor and Welfare
Japan: Pharmaceuticals and Medical Devices Agency
Lebanon: Institutional Review Board
Lebanon: Ministry of Public Health
Mexico: Ethics Committee
Mexico: Federal Commission for Protection Against Health Risks
Mexico: Federal Commission for Sanitary Risks Protection
Mexico: Ministry of Health
Mexico: National Council of Science and Technology
Mexico: National Institute of Public Health, Health Secretariat
Netherlands: Independent Ethics Committee
Netherlands: Dutch Health Care Inspectorate
Netherlands: Medical Ethics Review Committee (METC)
Netherlands: Medicines Evaluation Board (MEB)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Poland: Ministry of Health
Poland: Ministry of Science and Higher Education
South Africa: Department of Health
South Africa: Medicines Control Council
South Africa: National Health Research Ethics Council
Spain: Comité Ético de Investigación Clínica
Spain: Ethics Committee
Spain: Ministry of Health
Spain: Ministry of Health and Consumption
Spain: Spanish Agency of Medicines
Switzerland: Ethikkommission
Switzerland: Federal Office of Public Health
Switzerland: Laws and standards
Switzerland: Swissmedic
Thailand: Ethical Committee
Thailand: Food and Drug Administration
Thailand: Khon Kaen University Ethics Committee for Human Research
Thailand: Ministry of Public Health
Turkey: Ethics Committee
Turkey: Ministry of Health
United Kingdom: Department of Health
United Kingdom: Food Standards Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Health Service
United Kingdom: Research Ethics Committee
United States: Federal Government

Keywords provided by Novartis:
Tumor vascular disrupting agent
VDA
ASA404
non-small cell lung cancer
NSCLC

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Vadimezan
Docetaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014