A Study of ASA404 or Placebo in Combination With Docetaxel in Second-line Treatment for (Stage IIIb/IV) Non-small Cell Lung Cancer
- Conditions
- Non-Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT00738387
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 900
-
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.)
-
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
-
Age ≥ 18 years old
-
WHO Performance Status of 0-2
-
Not applicable per amendment#2
-
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.
-
Life expectancy ≥ 12 weeks
-
Written informed consent obtained according to local guidelines
-
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).
-
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.
-
Radiotherapy ≤ 2 weeks prior to randomization. Patients must have recovered from all acute radiotherapy-related toxicities.
-
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.
-
Treatment with all prior anticancer therapies ≤ 3 weeks prior to randomization (≤ 6 weeks for bevacizumab, mitomycin and nitrosoureas)
-
Concurrent use of other investigational agents and patients who have received investigational agents ≤ 4 weeks prior to randomization
-
Prior treatment with docetaxel for NSCLC in the locally advanced or metastatic first-line setting
-
Prior treatment with VDAs or tumor - VDAs
-
Any medical condition resulting in ≥ CTC grade 2 dyspnea
-
Patients with systolic BP > 160 mm Hg and/or diastolic BP > 90 mm Hg while on medication for hypertension
-
Patients with recent hemoptysis associated with NSCLC (>1 teaspoon in a single episode within 4 weeks)
-
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
-
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.
-
Known allergy or hypersensitivity to docetaxel or drugs formulated with polysorbate 80
-
Peripheral sensory neuropathy with functional impairment (CTC grade 2 neuropathy, regardless of causality)
-
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)
-
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/)
-
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).
-
Significant neurologic or psychiatric disorder which could compromise participation in the study
-
Patient unwilling or unable to comply with the protocol
-
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + docetaxel Placebo 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 ASA404 + docetaxel ASA404 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 ASA404 + docetaxel 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 Placebo + docetaxel 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
- Primary Outcome Measures
Name Time Method Overall survival Every 6 weeks from study treatment discontinuation until death or loss to follow-up
- Secondary Outcome Measures
Name Time Method Biomarker assessments 1 hr post-study drug at cycles 1, 2, 4, 6 and End of Treatment 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 Pharmacokinetic assessments 1 hr post-study drug, optional 3-5 hr post-study drug at cycles 1, 2, 3, 4, 5 and 6 Quality of life At every odd cycle and at end of treatment
Trial Locations
- Locations (90)
UT Southwester Med Ctr at Dallas
🇺🇸Dallas, Texas, United States
Texas Cancer Center - Denton
🇺🇸Denton, Texas, United States
Longview Cancer Center
🇺🇸Longview, Texas, United States
Texas Oncology - Allison Cancer Center
🇺🇸Midland, Texas, United States
Texas Cancer Center - Sherman
🇺🇸Sherman, Texas, United States
Tyler Cancer Center
🇺🇸Tyler, Texas, United States
Blood and Cancer Center of East Texas
🇺🇸Tyler, Texas, United States
Texas Oncology Cancer Care Center & Research Center
🇺🇸Waco, Texas, United States
Evergreen Hematology and Oncology
🇺🇸Spokane, Washington, United States
MultiCare Health System
🇺🇸Tacoma, Washington, United States
Northwest Cancer Specialists
🇺🇸Vancouver, Washington, United States
Novartis InvestigativeSite
🇮🇹Udine, Italy
Novartis Investigative Site
🇨🇭Geneve, Switzerland
Novartis investigative Site
🇪🇸Sabadell, Spain
Novartis Investigative site
🇨🇭St. Gallen, Switzerland
Paris Regional Cancer Center
🇺🇸Paris, Texas, United States
Puget Sound Cancer Centers
🇺🇸Edmonds, Washington, United States
MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
Fred Hutchinson Cancer Reseach Center
🇺🇸Seattle, Washington, United States
Puget Sound Cancer Center
🇺🇸Seattle, Washington, United States
California Pacific Medical Research Institute
🇺🇸San Francisco, California, United States
University of California - SF
🇺🇸San Francisco, California, United States
Nevada Cancer Institute
🇺🇸Las Vegas, Nevada, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Cancer Center of Texas
🇺🇸Wichita, Kansas, United States
Kansas City Cancer care, Southwest
🇺🇸Overland Park, Kansas, United States
Rocky Mountain Cancer Center
🇺🇸Denver, Colorado, United States
Oncology Specialist, P.c.
🇺🇸Huntsville, Alabama, United States
Highlands Oncology Group
🇺🇸Bentonville, Arkansas, United States
Arizona Oncology
🇺🇸Tucson, Arizona, United States
Central Hematology Oncology Medical Group
🇺🇸Alhambra, California, United States
Comprehensive Blood and Cancer Center
🇺🇸Bakersfield, California, United States
Compassionate Cancer Care Medical Group
🇺🇸Riverside, California, United States
St. Jude Heritage Healthcare
🇺🇸Fullerton, California, United States
Beaver Medical Group, L.P.
🇺🇸Highland, California, United States
Scripps Clinic
🇺🇸La Jolla, California, United States
University of Southern Californa
🇺🇸Los Angeles, California, United States
UCLA
🇺🇸Los Angeles, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
North Valley Hematology/Oncology Medical Group
🇺🇸Northridge, California, United States
University of California Irvine Medical Center
🇺🇸Orange, California, United States
Ventura County Hematology/Oncology Specialists
🇺🇸Oxnard, California, United States
Bay Area Cancer Research Group
🇺🇸Pleasant Hill, California, United States
Palo Alto Medical Foundation - Camino Div.
🇺🇸Palo Alto, California, United States
Loma Linda Oncology Medical Group, Inc.
🇺🇸Redlands, California, United States
Stanford Cancer Center
🇺🇸Stanford, California, United States
Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Advanced Medical Specialties
🇺🇸Miami, Florida, United States
Florida Hospital Cancer Institute
🇺🇸Orlando, Florida, United States
Cancer Care Specialists of Central Illinois
🇺🇸Decatur, Illinois, United States
Florida Cancer Institute
🇺🇸New Port Richey, Florida, United States
Suburban Hematology-Oncology
🇺🇸Lawrenceville, Georgia, United States
Ocala Oncology Center
🇺🇸Ocala, Florida, United States
Cancer Centers of Florida, PA
🇺🇸Orlando, Florida, United States
Hematology/Oncology Associates of Treasure Coast
🇺🇸Port Saint Lucie, Florida, United States
OSF Center for Cancer Care
🇺🇸Rockford, Illinois, United States
Cancer Care & Hematology Specialists of Chicagoland
🇺🇸Niles, Illinois, United States
Comprehensive Cancer Program
🇺🇸Harvey, Illinois, United States
Loyola Cancer Care and Research Center
🇺🇸Winfield, Illinois, United States
Central Indiana Cancer Centers
🇺🇸Indianapolis, Indiana, United States
Horizon Oncology Center
🇺🇸Lafayette, Indiana, United States
Siouxland Hematology-Oncology Associates
🇺🇸Sioux City, Iowa, United States
Providence Medical Group
🇺🇸Terre Haute, Indiana, United States
Western Kentucky Hematology & Oncology
🇺🇸Paducah, Kentucky, United States
James Graham Brown Cancer Center
🇺🇸Louisville, Kentucky, United States
Harry & Jeannette Weinberg Cancer Institute
🇺🇸Baltimore, Maryland, United States
St. John's Mercy Medical Center
🇺🇸Saint Louis, Missouri, United States
Missouri Cancer Associates
🇺🇸Columbia, Missouri, United States
New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
NY Oncology/Hematology - Latham
🇺🇸Latham, New York, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Cancer Center of North Carolina
🇺🇸Raleigh, North Carolina, United States
Advanced Oncology Associates
🇺🇸Armonk, New York, United States
Arena Oncology Associates, P.C.
🇺🇸Lake Success, New York, United States
Winthrop Hematology/Oncology
🇺🇸Mineola, New York, United States
Hematology Oncology Consultants, Inc.
🇺🇸Columbus, Ohio, United States
Signal Point Hematology/Oncology, Inc.
🇺🇸Middletown, Ohio, United States
St. Luke's Hospital & Healtth Network
🇺🇸Bethlehem, Pennsylvania, United States
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Texas Cancer center - Abilene
🇺🇸Abilene, Texas, United States
Texas Oncology - Arlington South
🇺🇸Arlington, Texas, United States
Texas Oncology at Presbyterian Hospital
🇺🇸Dallas, Texas, United States
Mamie McFadden Ward Cancer Ctr, Texas Oncology
🇺🇸Beaumont, Texas, United States
Texas Cancer Center at Medical City
🇺🇸Dallas, Texas, United States
Methodist Charlton Cancer Center
🇺🇸Dallas, Texas, United States
Kaiser Permanante, Northwest Region
🇺🇸Portland, Oregon, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Henderson, Nevada, United States
Hollings Cancer Center
🇺🇸Charleston, South Carolina, United States
University of Kansas Medical Center
🇺🇸Westwood, Kansas, United States