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

Phase 3

Terminated

• Conditions: Non-Small Cell Lung Cancer
• Interventions: Drug: Placebo; Drug: ASA404; Drug: carboplatin; Drug: Paclitaxel

• Registration Number: NCT00662597
• Lead Sponsor: Novartis Pharmaceuticals

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2008-04
• Study First Submitted: 2008-04-17
• Study First Submitted QC: 2008-04-17
• Study First Posted: 2008-04-21
• Primary Completion: 2010-05
• Study Completion: 2010-05
• Status Verified: 2012-05
• Disposition First Submitted: 2012-05-01
• Disposition First Submitted QC: 2012-05-01
• Disposition First Posted: 2012-05-03
• Last Update Submitted: 2020-12-16
• Last Update Posted: 2020-12-24

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1285

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ASA40 Placebo	Placebo	-
ASA404	ASA404	-
ASA40 Placebo	Paclitaxel	-
ASA404	carboplatin	-
ASA404	Paclitaxel	-
ASA40 Placebo	carboplatin	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (101)

Loyola University Medical Center; 🇺🇸 Maywood, Illinois, United States

Sinai Hospital of Baltimore - The Alvin & Lois Lapidus Cancer Institute; 🇺🇸 Baltimore, Maryland, United States

Arlington Cancer Center; 🇺🇸 Arlington, Texas, United States

University of Arizona Cancer Center; 🇺🇸 Tucson, Arizona, United States

Highlands Oncology Group; 🇺🇸 Bentonville, Arkansas, United States

Florida Cancer Specialists; 🇺🇸 Bradenton, Florida, United States

Hematology Oncology Specialists; 🇺🇸 Metairie, Louisiana, United States

Peninsula Regional Oncology and Hematology; 🇺🇸 Salisbury, Maryland, United States

Advocate Illinois Masonic Medical Center; 🇺🇸 Chicago, Illinois, United States

Boston VA Healthcare System; 🇺🇸 Boston, Massachusetts, United States

Novartis Investigative Site; 🇬🇧 Sutton, United Kingdom

Oncology Hematology Care Research; 🇺🇸 Cincinnati, Ohio, United States

Alta Bates Summit Medical Center; 🇺🇸 Berkeley, California, United States

Loma Linda University Cancer Center; 🇺🇸 Loma Linda, California, United States

Moores UCSD Cancer Center; 🇺🇸 La Jolla, California, United States

Ft. Wayne Oncology and Hematology; 🇺🇸 Fort Wayne, Indiana, United States

Loyola Cancer Care & Research Ctr. at Central Dupage Hospital; 🇺🇸 Winfield, Illinois, United States

Center for Cancer Care and Research (US Oncology); 🇺🇸 Saint Louis, Missouri, United States

New York Oncology Hematology; 🇺🇸 Latham, New York, United States

University of Oklahoma Health Science Center; 🇺🇸 Oklahoma City, Oklahoma, United States

California Pacific Medical Research Institute; 🇺🇸 San Francisco, California, United States

University of Nebraska Medical Center; 🇺🇸 Omaha, Nebraska, United States

Kaiser Permanente, Northwest Region; 🇺🇸 Portland, Oregon, United States

University of South Alabama/Mitchell Cancer Institute; 🇺🇸 Mobile, Alabama, United States

Arizona Oncology Associates; 🇺🇸 Tucson, Arizona, United States

Genesis Cancer Center; 🇺🇸 Hot Springs, Arkansas, United States

Pacific Oncology and Hematology Association; 🇺🇸 Encinitas, California, United States

Cancer Care Associates; 🇺🇸 Fresno, California, United States

California Cancer Care; 🇺🇸 Greenbrae, California, United States

Ronald Yanagihara - Private Practice; 🇺🇸 Gilroy, California, United States

Cedars Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

University of California Irvine Comprhensive Center; 🇺🇸 Orange, California, United States

Loma Linda Oncology Medical Group, Inc.; 🇺🇸 Redlands, California, United States

Redwood Regional Cancer Center; 🇺🇸 Santa Rosa, California, United States

Georgetown University Hospital; 🇺🇸 Washington, District of Columbia, United States

Palm Beach Institute of Hematology & Oncology; 🇺🇸 Boynton Beach, Florida, United States

Advanced Medical Specialties (ACORN); 🇺🇸 Miami, Florida, United States

Cancer Centers of Central Florida, PA; 🇺🇸 Leesburg, Florida, United States

Northwest Georgia Oncology Centers; 🇺🇸 Marietta, Georgia, United States

Kootenai Cancer Center (ACORN); 🇺🇸 Coeur d'Alene, Idaho, United States

Illinois Oncology/Warren Billhartz Cancer Ctr.; 🇺🇸 Maryville, Illinois, United States

Hematology/Oncology of North Shore; 🇺🇸 Skokie, Illinois, United States

Siouxland Hematology-Oncology Assoc., LLC; 🇺🇸 Sioux City, Iowa, United States

Kansas City Cancer Center, Southwest; 🇺🇸 Overland Park, Kansas, United States

St. Agnes Cancer Center; 🇺🇸 Baltimore, Maryland, United States

Louisiana State University Health Sciences Center - Feist-Weiller Cancer Center; 🇺🇸 Shreveport, Louisiana, United States

The Harry and Jeanette Weinberg Cancer Institute at Franklin Square/MedStar Health; 🇺🇸 Baltimore, Maryland, United States

Fallon Clinic; 🇺🇸 Worcester, Massachusetts, United States

Breslin Cancer Center; 🇺🇸 Lansing, Michigan, United States

Osteopathic Medical Oncology and Hematology PC; 🇺🇸 Woodhaven, Michigan, United States

St. Luke's Hospital - St Luke's Cancer Center; 🇺🇸 Duluth, Minnesota, United States

St. Louis University Cancer Center; 🇺🇸 Saint Louis, Missouri, United States

St. Louis Cancer and Breast Institute; 🇺🇸 Saint Louis, Missouri, United States

St. John's Mercy Medical Center; 🇺🇸 Saint Louis, Missouri, United States

Billings Clinic; 🇺🇸 Billings, Montana, United States

Sletten Cancer Institute; 🇺🇸 Great Falls, Montana, United States

Arena Oncology Associates; 🇺🇸 Lake Success, New York, United States

Hematology Oncology Associates of Rockland; 🇺🇸 Nyack, New York, United States

Syracuse VA Medical Center; 🇺🇸 Syracuse, New York, United States

Carolina Cancer Mgmt/Cape Fear Valley Health System/Med Onc; 🇺🇸 Fayetteville, North Carolina, United States

Alamance Regional Medical Center-Cancer Ctr.; 🇺🇸 Burlington, North Carolina, United States

Akron City Hospital; 🇺🇸 Akron, Ohio, United States

University Hospitals of Cleveland; 🇺🇸 Cleveland, Ohio, United States

Medical Oncology Hematology Associates, Inc. - Dayton Clinical Oncology Program; 🇺🇸 Dayton, Ohio, United States

Medical Oncology Hematology Associates, Inc.; 🇺🇸 Dayton, Ohio, United States

Cleo Craig Memorial Cancer Ctr. & Research Clinic; 🇺🇸 Lawton, Oklahoma, United States

South Carolina Oncology Associate; 🇺🇸 Columbia, South Carolina, United States

Allegheny General Hospital/Allegheny Cancer Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Chattanooga Oncology Hematology Associates; 🇺🇸 Chattanooga, Tennessee, United States

Lowcountry Hematology & Oncology PA; 🇺🇸 Mount Pleasant, South Carolina, United States

The West Clinic; 🇺🇸 Memphis, Tennessee, United States

Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

Texas Oncology Cancer Center of the High Plains; 🇺🇸 Amarillo, Texas, United States

Patient's Comprehensive Cancer Center; 🇺🇸 Carrollton, Texas, 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

HOPE Oncology; 🇺🇸 Richardson, Texas, United States

Texas Oncology at Garland; 🇺🇸 Garland, Texas, United States

Tyler Cancer Center; 🇺🇸 Tyler, Texas, United States

UT Health Center; 🇺🇸 Tyler, Texas, United States

Deke Slayton Cancer Center; 🇺🇸 Webster, Texas, United States

Texoma Cancer Center; 🇺🇸 Wichita Falls, Texas, United States

Northern Utah Associates; 🇺🇸 Ogden, Utah, United States

Danville Hematology & Oncology; 🇺🇸 Danville, Virginia, United States

Medical Oncology & Hematology Associates of Northern Virginia; 🇺🇸 Fairfax, Virginia, United States

Northwest Cancer Specialists; 🇺🇸 Vancouver, Washington, United States

Highline Medical Oncology; 🇺🇸 Burien, Washington, United States

Providence Everett Medical Center/Providence regional Cancer Partnership; 🇺🇸 Everett, Washington, United States

Medical Consultants; 🇺🇸 Milwaukee, Wisconsin, United States

Medical College of Wisconsin/Division of Neoplastic & Related Disorders; 🇺🇸 Milwaukee, Wisconsin, United States

UC Davis Comprehensive Cancer Center; 🇺🇸 Sacramento, California, United States

University of Louisville - James Graham Brown Cancer Center; 🇺🇸 Louisville, Kentucky, United States

Cancer Research Center of Hawaii; 🇺🇸 Honolulu, Hawaii, United States

Kansas City Veterans Affair Medical Center; 🇺🇸 Kansas City, Missouri, United States

Eastchester Center for Cancer Care; 🇺🇸 Bronx, New York, United States

Virginia Cancer Institute; 🇺🇸 Richmond, Virginia, United States

University of Wisconsin; 🇺🇸 Madison, Wisconsin, United States

Rochester General Hospital - Lipson Cancer Center; 🇺🇸 Rochester, New York, United States

Virginia Oncology Associates; 🇺🇸 Norfolk, Virginia, United States