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)

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)

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

Study Overview

• Status: Terminated
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: ASA404; Drug: docetaxel; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 900
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium
    • Novartis Investigative Site
  • Arlon, Belgium
    • Novartis Investigative Site
  • Bruxelles, Belgium
    • Novartis Investigative Site
  • Genk, Belgium
    • Novartis Investigative Site
  • Gent, Belgium
    • Novartis Investigative Site
  • Leuven, Belgium
    • Novartis Investigative Site
  • Liege, Belgium
    • Novartis Investigative Site
  • Namur, Belgium
    • Novartis Investigative Site
• Canada
  • Edmonton, Canada
    • Novartis Investigative Site
  • Greenfield Park, Canada
    • Novartis Investigative Site
  • Laval, Canada
    • Novartis Investigative Site
  • Montreal, Canada
    • Novartis Investigative Site
  • Toronto, Canada
    • Novartis Investigative Site
  • Trois-Rivieres, Canada
    • Novartis Investigative Site
  • Vancouver, Canada
    • Novartis Investigative Site
  • Weston, Canada
    • Novartis Investigative Site
  • Winnepeg, Canada
    • Novartis Investigative Site
• France
  • Avignon, France
    • Novartis Investigative Site
  • Brest, France
    • Novartis Investigative Site
  • Caen Cedex 5, France
    • Novartis Investigative Site
  • Caen Cedex 9, France
    • Novartis Investigative Site
  • La Chaussée Saint Victor, France
    • Novartis Investigative Site
  • Le mans Cedex, France
    • Novartis Investigative Site
  • Lille Cedex, France
    • Novartis Investigative Site
  • Nimes, France
    • Novartis Investigative Site
  • Paris, France
    • Novartis Investigative Site
  • Perpignan, France
    • Novartis Investigative Site
  • Rennes cedex 5, France
    • Novartis Investigative Site
  • Vandoeuvre-les-Nancy, France
    • Novartis Investigative Site
• Germany
  • Bamberg, Germany
    • Novartis Investigative Site
  • Berlin, Germany
    • Novartis Investigative Site
  • Coswig, Germany
    • Novartis Investigative Site
  • Eschweiler, Germany
    • Novartis Investigative Site
  • Essen, Germany
    • Novartis Investigative Site
  • Freiburg, Germany
    • Novartis Investigative Site
  • Grosshansdorf, Germany
    • Novartis Investigative Site
  • Guestrow, Germany
    • Novartis Investigative Site
  • Halle, Germany
    • Novartis Investigative Site
  • Hamburg, Germany
    • Novartis Investigative Site
  • Hannover, Germany
    • Novartis Investigative Site
  • Hemer, Germany
    • Novartis Investigative Site
  • Koeln, Germany
    • Novartis Investigative Site
  • Leipzig, Germany
    • Novartis Investigative Site
  • Magdeburg, Germany
    • Novartis Investigative Site
  • Muenchen, Germany
    • Novartis Investigative Site
  • Muenster, Germany
    • Novartis Investigative Site
  • Oldenburg, Germany
    • Novartis Investigative Site
  • Ulm, Germany
    • Novartis Investigative Site
• Hungary
  • Deszk, Hungary
    • Novartis Investigative Site
  • Gyula, Hungary
    • Novartis Investigative Site
  • Szekesfehervar, Hungary
    • Novartis Investigative Site
  • Torokbalint, Hungary
    • Novartis Investigative Site
  • Zalaegerszeg-Pozva, Hungary
    • Novartis Investigative Site
• Italy
  • Ancona, Italy
    • Novartis Investigative Site
  • Aviano, Italy
    • Novartis Investigative Site
  • Bologna, Italy
    • Novartis Investigative Site
  • Cosenza, Italy
    • Novartis Investigative Site
  • Cremona, Italy
    • Novartis Investigative Site
  • Milano, Italy
    • Novartis Investigative Site
  • Mirano, Italy
    • Novartis Investigative Site
  • Monza, Italy
    • Novartis Investigative Site
  • Napoli, Italy
    • Novartis Investigative Site
  • Palermo, Italy
    • Novartis Investigative Site
  • Reggio Emilia, Italy
    • Novartis Investigative Site
  • Sassari, Italy
    • Novartis Investigative Site
  • Udine, Italy
    • Novartis InvestigativeSite
• Poland
  • Bialystok, Poland
    • Novartis Investigative Site
  • Lonza, Poland
    • Novartis Investigative Site
  • Szczecin, Poland
    • Novartis Investigative Site
  • Warszawa, Poland
    • Novartis Investigative Site
• Spain
  • Mataro, Spain
    • Novartis Investigative Site
  • Sabadell, Spain
    • Novartis Investigative Site
  • Santander, Spain
    • Novartis Investigative Site
• Switzerland
  • Geneve, Switzerland
    • Novartis Investigative Site
  • St. Gallen, Switzerland
    • Novartis Investigative Site
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35805
      • Oncology Specialist, P.c.
  • Arizona
    • Tucson, Arizona, United States, 85704
      • Arizona Oncology
  • Arkansas
    • Bentonville, Arkansas, United States, 72712
      • Highlands Oncology Group
  • California
    • Alhambra, California, United States, 91801
      • Central Hematology Oncology Medical Group
    • Bakersfield, California, United States, 93309
      • Comprehensive Blood And Cancer Center
    • Corona, California, United States, 92879
      • Compassionate Cancer Care Medical Group
    • Fountain Valley, California, United States, 92708
      • Compassionate Cancer Care Medical Group
    • Fullerton, California, United States, 92835
      • St. Jude Heritage Healthcare
    • Highland, California, United States, 92346
      • Beaver Medical Group, L.P.
    • La Jolla, California, United States, 92037
      • Scripps Clinic
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90095
      • UCLA
    • Los Angeles, California, United States, 90033-0800
      • University of Southern Californa
    • Northridge, California, United States, 91325
      • North Valley Hematology/Oncology Medical Group
    • Orange, California, United States, 92868
      • University of California Irvine Medical Center
    • Oxnard, California, United States, 93030
      • Ventura County Hematology/Oncology Specialists
    • Palo Alto, California, United States, 94301
      • Palo Alto Medical Foundation - Camino Div.
    • Pleasant Hill, California, United States, 94523
      • Bay Area Cancer Research Group
    • Redlands, California, United States, 92374
      • Loma Linda Oncology Medical Group, Inc.
    • Riverside, California, United States, 92501
      • Compassionate Cancer Care Medical Group
    • San Francisco, California, United States, 94115
      • California Pacific Medical Research Institute
    • San Francisco, California, United States, 94115
      • University of California - SF
    • Stanford, California, United States, 94305
      • Stanford Cancer Center
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 21113
      • Georgetown University Hospital
  • Florida
    • Miami, Florida, United States, 33176
      • Advanced Medical Specialties
    • New Port Richey, Florida, United States, 34655
      • Florida Cancer Institute
    • Ocala, Florida, United States, 34474
      • Ocala Oncology Center
    • Orlando, Florida, United States, 32804
      • Florida Hospital Cancer Institute
    • Orlando, Florida, United States, 32806
      • Cancer Centers of Florida, PA
    • Port Saint Lucie, Florida, United States, 34952
      • Hematology/Oncology Associates of Treasure Coast
  • Georgia
    • Lawrenceville, Georgia, United States, 30045
      • Suburban Hematology-Oncology
  • Illinois
    • Decatur, Illinois, United States, 62526
      • Cancer Care Specialists of Central Illinois
    • Harvey, Illinois, United States, 60426
      • Comprehensive Cancer Program
    • Niles, Illinois, United States, 60714
      • Cancer Care & Hematology Specialists of Chicagoland
    • Rockford, Illinois, United States, 61108-2472
      • OSF Center for Cancer Care
    • Winfield, Illinois, United States, 60190
      • Loyola Cancer Care and Research Center
  • Indiana
    • Indianapolis, Indiana, United States, 46219
      • Central Indiana Cancer Centers
    • Lafayette, Indiana, United States, 47905
      • Horizon Oncology Center
    • Terre Haute, Indiana, United States, 47802
      • Providence Medical Group
  • Iowa
    • Sioux City, Iowa, United States, 51101
      • Siouxland Hematology-Oncology Associates
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • Kansas City Cancer care, Southwest
    • Westwood, Kansas, United States, 66205
      • University of Kansas Medical Center
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Texas
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • James Graham Brown Cancer Center
    • Paducah, Kentucky, United States, 42003
      • Western Kentucky Hematology & Oncology
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Harry & Jeannette Weinberg Cancer Institute
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Missouri Cancer Associates
    • Saint Louis, Missouri, United States, 63141
      • St. John's Mercy Medical Center
  • Nevada
    • Henderson, Nevada, United States, 89074
      • Comprehensive Cancer Centers of Nevada
    • Las Vegas, Nevada, United States, 89135
      • Nevada Cancer Institute
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • New Mexico Cancer Center
  • New York
    • Armonk, New York, United States, 10504
      • Advanced Oncology Associates
    • Lake Success, New York, United States, 11042
      • Arena Oncology Associates, P.C.
    • Latham, New York, United States, 12110
      • NY Oncology/Hematology - Latham
    • Mineola, New York, United States, 11501
      • Winthrop Hematology/Oncology
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Raleigh, North Carolina, United States, 27606
      • Cancer Center of North Carolina
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Columbus, Ohio, United States, 43235
      • Hematology Oncology Consultants, Inc.
    • Middletown, Ohio, United States, 45042
      • Signal Point Hematology/Oncology, Inc.
  • Oregon
    • Portland, Oregon, United States, 97227
      • Kaiser Permanante, Northwest Region
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • St. Luke's Hospital & Healtth Network
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Hollings Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Abilene, Texas, United States, 79606
      • Texas Cancer center - Abilene
    • Arlington, Texas, United States, 76014-2084
      • Texas Oncology - Arlington South
    • Beaumont, Texas, United States, 77702-1449
      • Mamie McFadden Ward Cancer Ctr, Texas Oncology
    • Dallas, Texas, United States, 75230
      • Texas Cancer Center at Medical City
    • Dallas, Texas, United States, 75237
      • Methodist Charlton Cancer Center
    • Dallas, Texas, United States, 75231
      • Texas Oncology at Presbyterian Hospital
    • Dallas, Texas, United States, 75390
      • UT Southwester Med Ctr at Dallas
    • Denton, Texas, United States, 76210
      • Texas Cancer Center - Denton
    • Longview, Texas, United States, 75601
      • Longview Cancer Center
    • Midland, Texas, United States, 79701
      • Texas Oncology - Allison Cancer Center
    • Paris, Texas, United States, 75460
      • Paris Regional Cancer Center
    • Sherman, Texas, United States, 75090
      • Texas Cancer Center - Sherman
    • Tyler, Texas, United States, 75702
      • Tyler Cancer Center
    • Tyler, Texas, United States, 75791
      • Blood and Cancer Center of East Texas
    • Waco, Texas, United States, 76712
      • Texas Oncology Cancer Care Center & Research Center
  • Washington
    • Edmonds, Washington, United States, 98026
      • Puget Sound Cancer Centers
    • Seattle, Washington, United States, 98133
      • Puget Sound Cancer Center
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Reseach Center
    • Spokane, Washington, United States, 99218
      • Evergreen Hematology and Oncology
    • Tacoma, Washington, United States, 98405
      • MultiCare Health System
    • Vancouver, Washington, United States, 98684
      • Northwest Cancer Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: docetaxel; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival	Every 6 weeks from study treatment discontinuation until death or loss to follow-up

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression free survival	Every 6 weeks from study treatment discontinuation until documented PD, death or loss to follow-up
Overall response rate	Every 42 days (=/- 7 days) from date of randomization until PD
Quality of life	At every odd cycle and at end of treatment
Biomarker assessments	1 hr post-study drug at cycles 1, 2, 4, 6 and End of Treatment
Pharmacokinetic assessments	1 hr post-study drug, optional 3-5 hr post-study drug at cycles 1, 2, 3, 4, 5 and 6

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CASA404A2302 from the Novartis Clinical Trials Website

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: August 19, 2008
• First Submitted That Met QC Criteria: August 19, 2008
• First Posted (Estimate): August 20, 2008

Study Record Updates

• Last Update Posted (Actual): December 24, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: NSCLC; non-small cell lung cancer; Tumor vascular disrupting agent; VDA; ASA404
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Vadimezan
• Other Study ID Numbers: CASA404A2302; EUDRACT number: 2008-002309-38