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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)

Phase 3
18 Years
Not Enrolling
Non-Small Cell Lung Cancer

Thank you

Trial Information

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)

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

- 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

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

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

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

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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

Overall survival rate

Outcome Time Frame:

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.

Safety Issue:


Principal Investigator

Novartis Pharmaceuticals

Investigator Role:

Study Director

Investigator Affiliation:

Novartis Pharmaceuticals


United States: Food and Drug Administration

Study ID:




Start Date:

April 2008

Completion Date:

May 2010

Related Keywords:

  • Non-Small Cell Lung Cancer
  • Tumor vascular disrupting agent
  • VDA
  • ASA404
  • non-small cell lung cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



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Virginia Oncology Associates Newport News, Virginia  23606
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Arlington Cancer Center Arlington, Texas  76012
South Texas Cancer Institute San Antonio, Texas  78229
Florida Cancer Specialists Fort Myers, Florida  33901
Medical Oncology Hematology Associates, Inc. Dayton, Ohio  45409
Moores UCSD Cancer Center La Jolla, California  92093-0658
Arena Oncology Associates Great Neck, New York  11021
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Highlands Oncology Group Springdale, Arkansas  72764
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The West Clinic Memphis, Tennessee  38120
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New York Oncology Hematology Albany, New York  12208
University of Arizona Cancer Center Tucson, Arizona  85724
University of Wisconsin Madison,, Wisconsin  53792-5666
Medical Consultants Milwaukee, Wisconsin  53215-3690
Northwest Georgia Oncology Centers Marietta, Georgia  30060
Billings Clinic Billings, Montana  59107-7000
Deke Slayton Cancer Center Webster, Texas  77589
Syracuse VA Medical Center Syracuse, New York  13210
University of Oklahoma Health Science Center Oklahoma City, Oklahoma  73104
Fallon Clinic Worcester, Massachusetts  01605
Cancer Care Centers of South Texas San Antonio, Texas  78229
Loma Linda University Cancer Center Loma Linda, California  92354
Cancer Centers of Central Florida, PA Leesburg, Florida  34788
Tennessee Oncology Nashville, Tennessee  37203
Chattanooga Oncology Hematology Associates Chattanooga, Tennessee  37404
Sletten Cancer Institute Great Falls, Montana  59405
St. Louis University Cancer Center St. Louis, Missouri  63110
Hematology Oncology Associates of Rockland Nyack, New York  10960
University of Louisville - James Graham Brown Cancer Center Louisville, Kentucky  40202
Hematology Oncology Specialists Metairie, Louisiana  70006
University of South Alabama/Mitchell Cancer Institute Mobile, Alabama  36604
Alta Bates Summit Medical Center Berkeley, California  94704
Pacific Oncology and Hematology Association Encinitas, California  92024
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University of California Irvine Comprhensive Center Orange, California  92868
Loma Linda Oncology Medical Group, Inc. Redlands, California  92374
California Pacific Medical Research Institute San Francisco, California  94115
Redwood Regional Cancer Center Santa Rosa, California  95403
Palm Beach Institute of Hematology & Oncology Boynton Beach, Florida  33435
Advanced Medical Specialties (ACORN) Miami, Florida  33176
Kootenai Cancer Center (ACORN) Couer D'Alene, Idaho  83814
Advocate Illinois Masonic Medical Center Chicago, Illinois  60657
Illinois Oncology/Warren Billhartz Cancer Ctr. Maryville, Illinois  62062
Hematology/Oncology of North Shore Skokie, Illinois  60076
Loyola Cancer Care & Research Ctr. at Central Dupage Hospital Winfield, Illinois  60190
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Siouxland Hematology-Oncology Assoc., LLC Sioux City, Iowa  51101
Kansas City Cancer Center, Southwest Overland Park, Kansas  66210
Louisiana State University Health Sciences Center - Feist-Weiller Cancer Center Shreveport, Louisiana  71103
The Harry and Jeanette Weinberg Cancer Institute at Franklin Square/MedStar Health Baltimore, Maryland  21237
Sinai Hospital of Baltimore - The Alvin & Lois Lapidus Cancer Institute Baltimore, Maryland  21215-5271
Peninsula Regional Oncology and Hematology Salisbury, Maryland  21801
Boston VA Healthcare System Boston, Massachusetts  02130
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St. Louis Cancer and Breast Institute St. Louis, Missouri  63141
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Medical Oncology Hematology Associates, Inc. - Dayton Clinical Oncology Program Dayton, Ohio  45429
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Kaiser Permanente, Northwest Region Portland, Oregon  97227
Allegheny General Hospital/Allegheny Cancer Center Pittsburg, Pennsylvania  15212
South Carolina Oncology Associate Columbia, South Carolina  29210
Lowcountry Hematology & Oncology PA Mt. Pleasant, South Carolina  29464
Texas Oncology Cancer Center of the High Plains Amarillo, Texas  79106
Patient's Comprehensive Cancer Center Carrolton, Texas  75010
Texas Oncology at Presbyterian Hospital Dallas, Texas  75231
University of Texas Southwestern Medical Center/Simmons Comprehensive Cancer Center Dallas, Texas  75390-9179
Texas Oncology at Garland Garland, Texas  75042
UT Health Center Tyler, Texas  75709
Danville Hematology & Oncology Danville, Virginia  24541
Medical Oncology & Hematology Associates of Northern Virginia Fairfax, Virginia  22031
Providence Everett Medical Center/Providence regional Cancer Partnership Everett, Washington  98201
Medical College of Wisconsin/Division of Neoplastic & Related Disorders Milwaukee, Wisconsin  53226