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

Non-Small Cell Lung Cancer Clinical Trial

— ATTRACT-2  

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00738387
• Other study ID #: CASA404A2302
• Secondary ID: EUDRACT number:
• Status: Terminated
• Phase: Phase 3
• Start date: December 2008

Study information

• Verified date: May 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 900
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

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

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	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
Canada	Novartis Investigative Site	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
France	Novartis Investigative Site	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
Germany	Novartis Investigative site	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
Hungary	Novartis Investigative site	Deszk
Hungary	Novartis Investigative Site	Gyula
Hungary	Novartis Investigative Site	Szekesfehervar
Hungary	Novartis Investigative Site	Torokbalint
Hungary	Novartis Investigative Site	Zalaegerszeg-Pozva
Italy	Novartis Investigative Site	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 InvestigativeSite	Udine
Poland	Novartis Investigative Site	Bialystok
Poland	Novartis Investigative Site	Lonza
Poland	Novartis Investigative Site	Szczecin
Poland	Novartis Investigative Site	Warszawa
Spain	Novartis Investigative Site	Mataro
Spain	Novartis investigative Site	Sabadell
Spain	Novartis Investigative Site	Santander
Switzerland	Novartis Investigative Site	Geneve
Switzerland	Novartis Investigative site	St. Gallen
United States	Texas Cancer center - Abilene	Abilene	Texas
United States	New Mexico Cancer Center	Albuquerque	New Mexico
United States	Central Hematology Oncology Medical Group	Alhambra	California
United States	Texas Oncology - Arlington South	Arlington	Texas
United States	Advanced Oncology Associates	Armonk	New York
United States	Comprehensive Blood and Cancer Center	Bakersfield	California
United States	Harry & Jeannette Weinberg Cancer Institute	Baltimore	Maryland
United States	Mamie McFadden Ward Cancer Ctr, Texas Oncology	Beaumont	Texas
United States	Highlands Oncology Group	Bentonville	Arkansas
United States	St. Luke's Hospital & Healtth Network	Bethlehem	Pennsylvania
United States	Hollings Cancer Center	Charleston	South Carolina
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Missouri Cancer Associates	Columbia	Missouri
United States	Hematology Oncology Consultants, Inc.	Columbus	Ohio
United States	Compassionate Cancer Care Medical Group	Corona	California
United States	Methodist Charlton Cancer Center	Dallas	Texas
United States	Texas Cancer Center at Medical City	Dallas	Texas
United States	Texas Oncology at Presbyterian Hospital	Dallas	Texas
United States	UT Southwester Med Ctr at Dallas	Dallas	Texas
United States	Cancer Care Specialists of Central Illinois	Decatur	Illinois
United States	Texas Cancer Center - Denton	Denton	Texas
United States	Rocky Mountain Cancer Center	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	Puget Sound Cancer Centers	Edmonds	Washington
United States	Compassionate Cancer Care Medical Group	Fountain Valley	California
United States	St. Jude Heritage Healthcare	Fullerton	California
United States	Comprehensive Cancer Program	Harvey	Illinois
United States	Comprehensive Cancer Centers of Nevada	Henderson	Nevada
United States	Beaver Medical Group, L.P.	Highland	California
United States	Oncology Specialist, P.c.	Huntsville	Alabama
United States	Central Indiana Cancer Centers	Indianapolis	Indiana
United States	Scripps Clinic	La Jolla	California
United States	Horizon Oncology Center	Lafayette	Indiana
United States	Arena Oncology Associates, P.C.	Lake Success	New York
United States	Nevada Cancer Institute	Las Vegas	Nevada
United States	NY Oncology/Hematology - Latham	Latham	New York
United States	Suburban Hematology-Oncology	Lawrenceville	Georgia
United States	Longview Cancer Center	Longview	Texas
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	UCLA	Los Angeles	California
United States	University of Southern Californa	Los Angeles	California
United States	James Graham Brown Cancer Center	Louisville	Kentucky
United States	Advanced Medical Specialties	Miami	Florida
United States	Signal Point Hematology/Oncology, Inc.	Middletown	Ohio
United States	Texas Oncology - Allison Cancer Center	Midland	Texas
United States	Winthrop Hematology/Oncology	Mineola	New York
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Florida Cancer Institute	New Port Richey	Florida
United States	Cancer Care & Hematology Specialists of Chicagoland	Niles	Illinois
United States	North Valley Hematology/Oncology Medical Group	Northridge	California
United States	Ocala Oncology Center	Ocala	Florida
United States	University of California Irvine Medical Center	Orange	California
United States	Cancer Centers of Florida, PA	Orlando	Florida
United States	Florida Hospital Cancer Institute	Orlando	Florida
United States	Kansas City Cancer care, Southwest	Overland Park	Kansas
United States	Ventura County Hematology/Oncology Specialists	Oxnard	California
United States	Western Kentucky Hematology & Oncology	Paducah	Kentucky
United States	Palo Alto Medical Foundation - Camino Div.	Palo Alto	California
United States	Paris Regional Cancer Center	Paris	Texas
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Bay Area Cancer Research Group	Pleasant Hill	California
United States	Hematology/Oncology Associates of Treasure Coast	Port Saint Lucie	Florida
United States	Kaiser Permanante, Northwest Region	Portland	Oregon
United States	Cancer Center of North Carolina	Raleigh	North Carolina
United States	Loma Linda Oncology Medical Group, Inc.	Redlands	California
United States	Compassionate Cancer Care Medical Group	Riverside	California
United States	OSF Center for Cancer Care	Rockford	Illinois
United States	St. John's Mercy Medical Center	Saint Louis	Missouri
United States	California Pacific Medical Research Institute	San Francisco	California
United States	University of California - SF	San Francisco	California
United States	Fred Hutchinson Cancer Reseach Center	Seattle	Washington
United States	Puget Sound Cancer Center	Seattle	Washington
United States	Texas Cancer Center - Sherman	Sherman	Texas
United States	Siouxland Hematology-Oncology Associates	Sioux City	Iowa
United States	Evergreen Hematology and Oncology	Spokane	Washington
United States	Stanford Cancer Center	Stanford	California
United States	SUNY Upstate Medical University	Syracuse	New York
United States	MultiCare Health System	Tacoma	Washington
United States	Providence Medical Group	Terre Haute	Indiana
United States	Arizona Oncology	Tucson	Arizona
United States	Blood and Cancer Center of East Texas	Tyler	Texas
United States	Tyler Cancer Center	Tyler	Texas
United States	Northwest Cancer Specialists	Vancouver	Washington
United States	Texas Oncology Cancer Care Center & Research Center	Waco	Texas
United States	Georgetown University Hospital	Washington	District of Columbia
United States	University of Kansas Medical Center	Westwood	Kansas
United States	Cancer Center of Texas	Wichita	Kansas
United States	Loyola Cancer Care and Research Center	Winfield	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Hungary,  Italy,  Poland,  Spain,  Switzerland, 

Outcome

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

External Links

•   Results for CASA404A2302 from the Novartis Clinical Trials Website