ASA404 or Placebo in Combination With Paclitaxel and Carboplatin as First-Line Treatment for Stage IIIb/IV Non-Small Cell Lung Cancer

Non-Small Cell Lung Cancer Clinical Trial

— ATRACT-1  

Official title:

A Phase III, Randomized, Double-Blind, Placebo-Controlled Multi-Center Study of ASA404 in Combination With Paclitaxel and Carboplatin as First-Line Treatment for Locally Advanced or Metastatic (Stage IIIb/IV) Non-Small Cell Lung Cancer (NSCLC)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00662597
• Other study ID #: CASA404A2301
• Status: Terminated
• Phase: Phase 3
• Start date: April 2008
• Est. completion date: May 2010

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 standard chemotherapy makes the cancer treatment more effective in patients with advanced lung cancer.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1285
• Est. completion date: May 2010
• Est. primary completion date: May 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. (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. Newly diagnosed Stage IIIb disease (malignant pleural effusion or pericardial effusion that have been confirmed cytologically) or Stage IV disease

3. No prior systemic antineoplastic treatment for Stage IIIb/IV non-small cell carcinoma of the lung (Prior neoadjuvant or adjuvant chemotherapy for earlier stage I/II NSCLC is allowed if 12 months or more prior to Baseline visit.)

4. Age = 18 years old

5. WHO Performance Status of 0-1

6. Measurable or non-measurable disease per RECIST criteria (Post-text supplement 1)

7. Lab 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)

• 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 IULN (Sections 6.9.1 and 7.3.4.2)

• Electrolyte values (potassium, calcium, magnesium) within > 1 x LLN and < 1 x ULN. Patients with corrected electrolyte values are eligible. See Sections 6.8.1 and 7.3.4.3.

• Females of child-bearing potential must have negative serum pregnancy test (confirmation of negative urine pregnancy test within 72 hours prior to initial dosing).

8. Life expectancy = 12 weeks

9. 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 a history of another primary malignancy = 5 years, with the exception of non-melanoma skin cancer or cervical cancer in situ.

3. Radiotherapy = 2 weeks prior to randomization. Patients must have recovered from all radiotherapy-related toxicities.

4. Major surgery = 4 weeks prior to randomization or minor surgery = 2 weeks prior to randomization.(Major surgery is defined by the use of general anesthesia however, endoscopic examinations with diagnostic intent are not considered major surgery. Insertion of a vascular access device is exempt from this exclusion criteria. Patients must have recovered from all surgery-related complications.

5. Concurrent use of other investigational agents and patients who have received investigational agents = 4 weeks prior to randomization

6. Prior exposure to Tumor-VDAs or other vascular targeting agents (anti-VEGF, anti-VEGF receptor agents, anti-EGFR agents [bevacizumab, cetuximab, etc.])

7. Pleural effusion that causes = CTC grade 2 dyspnea

8. Patients with systolic BP > 160 mm Hg and/or diastolic BP >90 mm Hg

9. Patients with recent hemoptysis associated with NSCLC (> 1 teaspoon in a single episode within 4 weeks)

10. 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

• 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

11. Concomitant use of drugs with a risk of causing Torsades de Pointes (See Table 6-3)

12. Known allergy or hypersensitivity to platinum-containing drugs, taxanes, other drugs formulated in Cremophor EL (polyoxyethylated castor oil) or any known excipients of these drugs.

13. Peripheral sensory neuropathy with functional impairment (CTC grade 2 neuropathy, regardless of causality)

14. 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)

15. 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 paclitaxel 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/)

16. 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).

17. Significant neurologic or psychiatric disorder which could compromise participation in the study Patient unwilling or unable to comply with the protocol

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

• Placebo

• carboplatin

• Paclitaxel

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Capital Federal
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	La Plata
Argentina	Novartis Investigative Site	Mendoza
Argentina	Novartis Investigative Site	Rosario
Australia	Novartis Investigative Site	Heidelberg
Australia	Novartis Investigative Site	Herston
Australia	Novartis Investigative Site	South Brisbane
Belgium	Novartis Investigative Site	Duffel
Belgium	Novartis Investigative Site	Jette
Belgium	Novartis Investigative Site	Liege
Brazil	Novartis Investigative Site	Barretos
Brazil	Novartis Investigative Site	Belo Horizonte
Brazil	Novartis Investigative Site	Goiania
Brazil	Novartis Investigative Site	Jaù
Brazil	Novartis Investigative Site	Jaú
Brazil	Novartis Investigative Site	Porto Alegre
Brazil	Novartis Investigative Site	Santo Andre
Brazil	Novartis Investigative Site	Sao Paulo
Brazil	Novartis Investigative Site	São Paulo
Canada	Novartis Investigative Site	Calgary
Canada	Novartis Investigative Site	Greenfield Park
Canada	Novartis Investigative Site	Kitchener
Canada	Novartis Investigative Site	London
Canada	Novartis Investigative Site	Moncton
Canada	Novartis Investigative Site	Montreal
Canada	Novartis Investigative Site	Rimouski
Canada	Novartis Investigative Site	Sainte-Foy
Canada	Novartis Investigative Site	Sherbrooke
Canada	Novartis Investigative Site	Sult Ste-Marie
China	Novartis Investigative Site	Bejing
China	Novartis Investigative Site	Guangzhou
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Wuhan
China	Novartis Investigative Site	Xi'an
Czechia	Novartis Investigative Site	Brno
Czechia	Novartis Investigative Site	Ostrava Poruba
Czechia	Novartis Investigative Site	Prague
France	Novartis Investigative Site	Bobigny
France	Novartis Investigative Site	Boujan-sur-Libron
France	Novartis Investigative Site	Clamart Cedex
France	Novartis Investigative Site	Le Mans
France	Novartis Investigative Site	Limoges
France	Novartis Investigative Site	Lyon Cedex
France	Novartis Investigative Site	Marseille
France	Novartis Investigative Site	Nice
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Saint Herblain
France	Novartis Investigative Site	Toulon Armées
France	Novartis Investigative Site	Tours Cedex 9
Germany	Novartis Investigative Site	Aschaffenburg
Germany	Novartis Investigative Site	Bad Berka
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Donaustauf
Germany	Novartis Investigative Site	Ebensberg
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Gerlingen
Germany	Novartis Investigative Site	Göttingen
Germany	Novartis Investigative Site	Grosshandsdorf
Germany	Novartis Investigative Site	Heidenheim
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Merseburg
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Nuernberg
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Heraklion Crete
Greece	Novartis Investigative Site	Thessaloniki
Hong Kong	Novartis Investigative Site	Hong Kong
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Deszk
Hungary	Novartis Investigative Site	Mátraháza
Israel	Novartis Investigative Site	Kfar-Sava
Israel	Novartis Investigative Site	Rehovot
Israel	Novartis Investigative Site	Tel-Aviv
Israel	Novartis Investigative Site	Tel-Hashomer
Israel	Novartis Investigative Site	Zrifin
Italy	Novartis Investigative Site	Avellino
Italy	Novartis Investigative Site	Milano
Italy	Novartis Investigative Site	Modena
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Orbassano
Italy	Novartis Investigative Site	Parma
Italy	Novartis Investigative Site	Perugia
Italy	Novartis Investigative Site	Roma
Japan	Novartis Investigative Site	Akashi
Japan	Novartis Investigative Site	Fukuoka
Japan	Novartis Investigative Site	Habikino
Japan	Novartis Investigative Site	Hiroshima
Japan	Novartis Investigative Site	Kashiwa
Japan	Novartis Investigative Site	Kobe-city
Japan	Novartis Investigative Site	Koto
Japan	Novartis Investigative Site	Kumamoto
Japan	Novartis Investigative Site	Kurashiki
Japan	Novartis Investigative Site	Matsuyama
Japan	Novartis Investigative Site	Nagoya
Japan	Novartis Investigative Site	Niigata
Japan	Novartis Investigative Site	Okayama
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Osaka Sayama
Japan	Novartis Investigative Site	Sapporo
Japan	Novartis Investigative Site	Sendai
Japan	Novartis Investigative Site	Ube
Japan	Novartis Investigative Site	Yokohama
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seungnam
Korea, Republic of	Novartis Investigative Site	Suwon
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Breda
Netherlands	Novartis Investigative Site	Eindhoven
Netherlands	Novartis Investigative Site	Harderwijk
Netherlands	Novartis Investigative Site	Hertogenbosch
Netherlands	Novartis Investigative Site	Zwolle
New Zealand	Novartis Investigative Site	Auckland
New Zealand	Novartis Investigative Site	Christchurch
New Zealand	Novartis Investigative Site	Hamilton
New Zealand	Novartis Investigative Site	Wellington
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Lublin
Poland	Novartis Investigative Site	Otwock
Poland	Novartis Investigative Site	Poznan
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Baracaldo
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Córdoba
Spain	Novartis Investigative Site	Granada
Spain	Novartis Investigative Site	Jaen
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Pontevedra
Spain	Novartis Investigative Site	Sevilla
Spain	Novartis Investigative Site	Zaragoza
Sweden	Novartis Investigative Site	Umea
Taiwan	Novartis Investigative Site	Kaoshiung
Taiwan	Novartis Investigative Site	Lin-Ko
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Tainan
Taiwan	Novartis Investigative Site	Taipei
Turkey	Novartis Investigative Site	Altunizade
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Izmir
United Kingdom	Novartis Investigative Site	Aberdeen
United Kingdom	Novartis Investigative Site	Cambridge
United Kingdom	Novartis Investigative Site	Leicester
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Manchester
United Kingdom	Novartis Investigative Site	Sutton
United States	Akron City Hospital	Akron	Ohio
United States	Texas Oncology Cancer Center of the High Plains	Amarillo	Texas
United States	Arlington Cancer Center	Arlington	Texas
United States	Sinai Hospital of Baltimore - The Alvin & Lois Lapidus Cancer Institute	Baltimore	Maryland
United States	St. Agnes Cancer Center	Baltimore	Maryland
United States	The Harry and Jeanette Weinberg Cancer Institute at Franklin Square/MedStar Health	Baltimore	Maryland
United States	Highlands Oncology Group	Bentonville	Arkansas
United States	Alta Bates Summit Medical Center	Berkeley	California
United States	Billings Clinic	Billings	Montana
United States	Boston VA Healthcare System	Boston	Massachusetts
United States	Palm Beach Institute of Hematology & Oncology	Boynton Beach	Florida
United States	Florida Cancer Specialists	Bradenton	Florida
United States	Eastchester Center for Cancer Care	Bronx	New York
United States	Highline Medical Oncology	Burien	Washington
United States	Alamance Regional Medical Center-Cancer Ctr.	Burlington	North Carolina
United States	Patient's Comprehensive Cancer Center	Carrollton	Texas
United States	Chattanooga Oncology Hematology Associates	Chattanooga	Tennessee
United States	Advocate Illinois Masonic Medical Center	Chicago	Illinois
United States	Oncology Hematology Care Research	Cincinnati	Ohio
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	Kootenai Cancer Center (ACORN)	Coeur d'Alene	Idaho
United States	South Carolina Oncology Associate	Columbia	South Carolina
United States	South Texas Cancer Institute	Corpus Christi	Texas
United States	Cancer Care Centers of South Texas	Dallas	Texas
United States	Texas Oncology at Presbyterian Hospital	Dallas	Texas
United States	University of Texas Southwestern Medical Center/Simmons Comprehensive Cancer Center	Dallas	Texas
United States	Danville Hematology & Oncology	Danville	Virginia
United States	Medical Oncology Hematology Associates, Inc.	Dayton	Ohio
United States	Medical Oncology Hematology Associates, Inc. - Dayton Clinical Oncology Program	Dayton	Ohio
United States	St. Luke's Hospital - St Luke's Cancer Center	Duluth	Minnesota
United States	Pacific Oncology and Hematology Association	Encinitas	California
United States	Providence Everett Medical Center/Providence regional Cancer Partnership	Everett	Washington
United States	Medical Oncology & Hematology Associates of Northern Virginia	Fairfax	Virginia
United States	Carolina Cancer Mgmt/Cape Fear Valley Health System/Med Onc	Fayetteville	North Carolina
United States	Ft. Wayne Oncology and Hematology	Fort Wayne	Indiana
United States	Cancer Care Associates	Fresno	California
United States	Texas Oncology at Garland	Garland	Texas
United States	Ronald Yanagihara - Private Practice	Gilroy	California
United States	Sletten Cancer Institute	Great Falls	Montana
United States	California Cancer Care	Greenbrae	California
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	Genesis Cancer Center	Hot Springs	Arkansas
United States	Kansas City Veterans Affair Medical Center	Kansas City	Missouri
United States	Moores UCSD Cancer Center	La Jolla	California
United States	Arena Oncology Associates	Lake Success	New York
United States	Breslin Cancer Center	Lansing	Michigan
United States	New York Oncology Hematology	Latham	New York
United States	Cleo Craig Memorial Cancer Ctr. & Research Clinic	Lawton	Oklahoma
United States	Cancer Centers of Central Florida, PA	Leesburg	Florida
United States	Loma Linda University Cancer Center	Loma Linda	California
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	University of Louisville - James Graham Brown Cancer Center	Louisville	Kentucky
United States	University of Wisconsin	Madison	Wisconsin
United States	Northwest Georgia Oncology Centers	Marietta	Georgia
United States	Illinois Oncology/Warren Billhartz Cancer Ctr.	Maryville	Illinois
United States	Loyola University Medical Center	Maywood	Illinois
United States	The West Clinic	Memphis	Tennessee
United States	Hematology Oncology Specialists	Metairie	Louisiana
United States	Advanced Medical Specialties (ACORN)	Miami	Florida
United States	Medical College of Wisconsin/Division of Neoplastic & Related Disorders	Milwaukee	Wisconsin
United States	Medical Consultants	Milwaukee	Wisconsin
United States	University of South Alabama/Mitchell Cancer Institute	Mobile	Alabama
United States	Lowcountry Hematology & Oncology PA	Mount Pleasant	South Carolina
United States	Tennessee Oncology	Nashville	Tennessee
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Hematology Oncology Associates of Rockland	Nyack	New York
United States	Northern Utah Associates	Ogden	Utah
United States	University of Oklahoma Health Science Center	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	University of California Irvine Comprhensive Center	Orange	California
United States	Kansas City Cancer Center, Southwest	Overland Park	Kansas
United States	Allegheny General Hospital/Allegheny Cancer Center	Pittsburgh	Pennsylvania
United States	Kaiser Permanente, Northwest Region	Portland	Oregon
United States	Loma Linda Oncology Medical Group, Inc.	Redlands	California
United States	HOPE Oncology	Richardson	Texas
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Rochester General Hospital - Lipson Cancer Center	Rochester	New York
United States	UC Davis Comprehensive Cancer Center	Sacramento	California
United States	Center for Cancer Care and Research (US Oncology)	Saint Louis	Missouri
United States	St. John's Mercy Medical Center	Saint Louis	Missouri
United States	St. Louis Cancer and Breast Institute	Saint Louis	Missouri
United States	St. Louis University Cancer Center	Saint Louis	Missouri
United States	Peninsula Regional Oncology and Hematology	Salisbury	Maryland
United States	California Pacific Medical Research Institute	San Francisco	California
United States	Redwood Regional Cancer Center	Santa Rosa	California
United States	Louisiana State University Health Sciences Center - Feist-Weiller Cancer Center	Shreveport	Louisiana
United States	Siouxland Hematology-Oncology Assoc., LLC	Sioux City	Iowa
United States	Hematology/Oncology of North Shore	Skokie	Illinois
United States	Syracuse VA Medical Center	Syracuse	New York
United States	Arizona Oncology Associates	Tucson	Arizona
United States	University of Arizona Cancer Center	Tucson	Arizona
United States	Tyler Cancer Center	Tyler	Texas
United States	UT Health Center	Tyler	Texas
United States	Northwest Cancer Specialists	Vancouver	Washington
United States	Georgetown University Hospital	Washington	District of Columbia
United States	Deke Slayton Cancer Center	Webster	Texas
United States	Texoma Cancer Center	Wichita Falls	Texas
United States	Loyola Cancer Care & Research Ctr. at Central Dupage Hospital	Winfield	Illinois
United States	Osteopathic Medical Oncology and Hematology PC	Woodhaven	Michigan
United States	Fallon Clinic	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  China,  Czechia,  France,  Germany,  Greece,  Hong Kong,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  New Zealand,  Poland,  Singapore,  Spain,  Sweden,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival rate		Patients will be followed every six weeks for survival following treatment completion, discontinuation, or documented disease progression until either death or the data cut off date.
Secondary	Overall survival of patients with squamous and non-squamous NSCLC		Patients will be followed every six weeks for survival following treatment completion, discontinuation, or documented disease progression until either death or the data cut off date.

External Links

•   Results for CASA404A2301 from the Novartis Clinical Trials website
•   Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.