Carboplatin, Paclitaxel, and Bevacizumab With or Without Erlotinib Hydrochloride in Treating Non-Smokers With Advanced Non-Small Cell Lung Cancer
- Conditions
- Recurrent Non-small Cell Lung CancerStage IIIB Non-small Cell Lung CancerStage IV Non-small Cell Lung Cancer
- Interventions
- Registration Number
- NCT00976677
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This randomized phase II trial studies how well carboplatin, paclitaxel, and bevacizumab work with or without erlotinib hydrochloride in treating non-smokers with advanced non-small cell lung cancer. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether giving combination chemotherapy together with bevacizumab is more effective with or without erlotinib hydrochloride in treating patients with non-small cell lung cancer.
- Detailed Description
PRIMARY OBJECTIVES:
I. To evaluate the progression-free survival (PFS) of non-smokers with advanced non-small cell lung cancer (NSCLC) randomized to standard of care (either carboplatin/paclitaxel with or without bevacizumab), or standard of care plus erlotinib hydrochloride.
SECONDARY OBJECTIVES:
I. To evaluate the overall survival from day of randomization. II. To evaluate response rate. III. To evaluate relative toxicity. IV. To determine the frequency of epidermal growth factor receptor (EGFR) and Kras mutations in non-smokers with NSCLC and correlate mutation status with response rate and progression free survival.
V. To obtain blood and tissue specimens for further marker-based exploratory analyses regarding EGFR inhibitors.
VI. To evaluate EGFR positivity by fluorescence in situ hybridization (FISH) as a predictor of improved PFS in patients treated with erlotinib hydrochloride.
OUTLINE: This is a multicenter study. Patients are stratified according to gender and eligibility for bevacizumab therapy (ineligible vs eligible and willing to receive bevacizumab vs eligible and not willing to receive bevacizumab). Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes (with or without bevacizumab IV over 30-90 minutes) on day 1. Patients also receive placebo orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients with stable or responding disease may continue to receive placebo (with or without bevacizumab) as above in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive paclitaxel and carboplatin (with or without bevacizumab) as in arm I. Patients also receive erlotinib hydrochloride PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients with stable or responding disease may continue to receive erlotinib hydrochloride (with or without bevacizumab) as above in the absence of disease progression or unacceptable toxicity.
Blood and tissue samples are collected for correlative laboratory studies.
After completion of study treatment, patients are followed up periodically for 5 years.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 10
-
Measurable disease as defined by Response Criteria In Solid Tumors (RECIST) criteria
-
Baseline measurements and evaluations of all sites of disease must be obtained =< 4 weeks (28 days) prior to randomization
-
Eastern Cooperative Oncology Group (ECOG) performance status between 0-1
-
No prior chemotherapy for lung cancer; prior chemotherapy for an unrelated condition is allowed if completed > 3 years prior to date of randomization
-
Histological or cytologic evidence of non-small cell lung cancer
-
Patients must not have any additional active, invasive malignancies requiring therapy
-
Patients must have smoked less than or equal to 100 cigarettes in their lifetime
-
Stage IV or IIIB (with pleural or pericardial effusion or multifocal pleural involvement) or recurrence after prior curative resection or definitive radiation
-
Prior radiation therapy (RT) is allowed, provided RT has ended at least 2 weeks (14 days) prior to date of randomization; patients must have recovered from any adverse events related to the RT (except alopecia and grade 1 neuropathy); no previous irradiation to the only site of measurable disease, unless that site has had subsequent evidence of pathologic or radiologic progression
-
Absolute neutrophil count (ANC) >= 1500/mm^3
-
Platelet count >= 100,000/mm^3
-
Bilirubin =< 1.5 mg/dl
-
Creatinine =< 2.0 mg/dl
-
Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvate transaminase (SGPT) =< 3 X institutional upper limit of normal (ULN)
-
Women must not be pregnant or breast-feeding due to unknown interaction between erlotinib and the developing fetus or newborns potentially exposed to erlotinib by ingestion of lactated milk; all females of childbearing potential must have a blood test within 2 weeks prior to randomization to rule out pregnancy
-
Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception
-
Patients must not have clinically significant ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
-
Patient must meet the following criteria:
- Non-squamous histology
- No antecedent hemoptysis
- International normalized ratio (INR) =< 3 within 4 weeks (28 days) prior to randomization
-
Patients may be on a stable regimen of therapeutic anticoagulation or may be receiving prophylactic anticoagulation of venous access devices, provided that coagulation studies met entry criteria; caution must be exercised for patients requiring anticoagulation, including treatment with low dose heparin or low molecular weight heparin for deep vein thrombosis (DVT) prophylaxis while on study due to an increased risk of bleeding with bevacizumab
-
No history of untreated brain metastases NOTE: Recent data (PASSPORT, ATLAS, AIRES) suggest that bevacizumab can be given in patients with treated brain metastases; investigators can use their discretion in deciding whether to use bevacizumab in patients who fulfill these criteria
-
Urine dipstick must be =< 0-1+ within 4 weeks (28 days) of randomization. If urine dipstick is > 1+ then the Urine Protein Creatinine (UPC) ratio must be calculated
-
Patients must have no history of thrombotic or hemorrhagic disorders
-
Patients with history of hypertension must be well-controlled (blood pressure [BP] =< 150/90 within 4 weeks [28 days] of randomization) and on a stable regimen of anti-hypertensive therapy (within 4 weeks of randomization)
-
Patients must not have serious non-healing wound ulcer, bone fracture, or major surgical procedure within 28 days prior to randomization
-
Patients with a known history of myocardial infarction or other evidence of arterial thrombotic disease (angina) will be allowed on study only if they have had no evidence of active disease for at least 6 months prior to randomization
-
Patients must not have a history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to randomization
-
Patients must not have significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to randomization
-
Patients must not have clinically significant cardiovascular disease including:
- History of cerebral vascular accident (CVA) within 6 months
- New York Heart Association grade II or greater congestive heart failure
- Serious and inadequately controlled cardiac arrhythmia
- Clinically significant peripheral vascular disease (symptomatic with intermittent claudications or < 6 months from a bypass operation)
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I bevacizumab Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes (with or without bevacizumab IV over 30-90 minutes) on day 1. Patients also receive placebo PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients with stable or responding disease may continue to receive placebo (with or without bevacizumab) as above in the absence of disease progression or unacceptable toxicity. Arm II erlotinib hydrochloride Patients receive paclitaxel and carboplatin (with or without bevacizumab) as in arm I. Patients also receive erlotinib hydrochloride PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients with stable or responding disease may continue to receive erlotinib hydrochloride (with or without bevacizumab) as above in the absence of disease progression or unacceptable toxicity. Arm II bevacizumab Patients receive paclitaxel and carboplatin (with or without bevacizumab) as in arm I. Patients also receive erlotinib hydrochloride PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients with stable or responding disease may continue to receive erlotinib hydrochloride (with or without bevacizumab) as above in the absence of disease progression or unacceptable toxicity. Arm I carboplatin Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes (with or without bevacizumab IV over 30-90 minutes) on day 1. Patients also receive placebo PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients with stable or responding disease may continue to receive placebo (with or without bevacizumab) as above in the absence of disease progression or unacceptable toxicity. Arm I paclitaxel Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes (with or without bevacizumab IV over 30-90 minutes) on day 1. Patients also receive placebo PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients with stable or responding disease may continue to receive placebo (with or without bevacizumab) as above in the absence of disease progression or unacceptable toxicity. Arm II carboplatin Patients receive paclitaxel and carboplatin (with or without bevacizumab) as in arm I. Patients also receive erlotinib hydrochloride PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients with stable or responding disease may continue to receive erlotinib hydrochloride (with or without bevacizumab) as above in the absence of disease progression or unacceptable toxicity. Arm II paclitaxel Patients receive paclitaxel and carboplatin (with or without bevacizumab) as in arm I. Patients also receive erlotinib hydrochloride PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients with stable or responding disease may continue to receive erlotinib hydrochloride (with or without bevacizumab) as above in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) Every 6 weeks during treatment and every 3 months in follow-up until disease progression or up to 5 years Progression-free survival (PFS) is defined to be the time from randomization to progression of disease or death, whichever occurs first. Progressive disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (108)
Illinois CancerCare-Havana
🇺🇸Havana, Illinois, United States
Mason District Hospital
🇺🇸Havana, Illinois, United States
Abramson Cancer Center of The University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Saint Paul Hospital
🇺🇸Dallas, Texas, United States
Parkland Memorial Hospital
🇺🇸Dallas, Texas, United States
Zale Lipshy University Hospital
🇺🇸Dallas, Texas, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
North Suburban Medical Center
🇺🇸Thornton, Colorado, United States
Saint Mary Corwin Medical Center
🇺🇸Pueblo, Colorado, United States
Sky Ridge Medical Center
🇺🇸Lone Tree, Colorado, United States
Swedish Medical Center
🇺🇸Englewood, Colorado, United States
Longmont United Hospital
🇺🇸Longmont, Colorado, United States
Saint Francis Hospital and Medical Center
🇺🇸Hartford, Connecticut, United States
North Colorado Medical Center
🇺🇸Greeley, Colorado, United States
Memorial Hospital
🇺🇸Carthage, Illinois, United States
Saint Joseph Medical Center
🇺🇸Bloomington, Illinois, United States
Illinois CancerCare-Macomb
🇺🇸Macomb, Illinois, United States
Spector, David MD (UIA Investigator)
🇺🇸Moline, Illinois, United States
Ingalls Memorial Hospital
🇺🇸Harvey, Illinois, United States
Illinois CancerCare-Community Cancer Center
🇺🇸Normal, Illinois, United States
Sharis, Christine M MD (UIA Investigator)
🇺🇸Moline, Illinois, United States
Illinois CancerCare-Peoria
🇺🇸Peoria, Illinois, United States
Illinois CancerCare-Peru
🇺🇸Peru, Illinois, United States
OSF Saint Francis Medical Center
🇺🇸Peoria, Illinois, United States
Illinois CancerCare-Ottawa Clinic
🇺🇸Ottawa, Illinois, United States
Siouxland Hematology Oncology Associates
🇺🇸Sioux City, Iowa, United States
Saint Luke's Regional Medical Center
🇺🇸Sioux City, Iowa, United States
Saint Joseph Mercy Port Huron
🇺🇸Port Huron, Michigan, United States
Lake University Ireland Cancer Center
🇺🇸Mentor, Ohio, United States
UHHS-Chagrin Highlands Medical Center
🇺🇸Orange Village, Ohio, United States
Bryn Mawr Hospital
🇺🇸Bryn Mawr, Pennsylvania, United States
Paoli Memorial Hospital
🇺🇸Paoli, Pennsylvania, United States
Hurley Medical Center
🇺🇸Flint, Michigan, United States
Saint Joseph Mercy Oakland
🇺🇸Pontiac, Michigan, United States
Allegiance Health
🇺🇸Jackson, Michigan, United States
Saint John Macomb-Oakland Hospital
🇺🇸Warren, Michigan, United States
Miller-Dwan Hospital
🇺🇸Duluth, Minnesota, United States
Illinois CancerCare-Princeton
🇺🇸Princeton, Illinois, United States
Exempla Saint Joseph Hospital
🇺🇸Denver, Colorado, United States
The Medical Center of Aurora
🇺🇸Aurora, Colorado, United States
Saint Anthony Central Hospital
🇺🇸Denver, Colorado, United States
Presbyterian - Saint Lukes Medical Center - Health One
🇺🇸Denver, Colorado, United States
Porter Adventist Hospital
🇺🇸Denver, Colorado, United States
Colorado Cancer Research Program CCOP
🇺🇸Denver, Colorado, United States
Saint Joseph Mercy Hospital
🇺🇸Ann Arbor, Michigan, United States
Michigan Cancer Research Consortium Community Clinical Oncology Program
🇺🇸Ann Arbor, Michigan, United States
Saint John Hospital and Medical Center
🇺🇸Detroit, Michigan, United States
Essentia Health Saint Mary's Medical Center
🇺🇸Duluth, Minnesota, United States
Essentia Health Duluth Clinic CCOP
🇺🇸Duluth, Minnesota, United States
Boulder Community Hospital
🇺🇸Boulder, Colorado, United States
Penrose-Saint Francis Healthcare
🇺🇸Colorado Springs, Colorado, United States
Rose Medical Center
🇺🇸Denver, Colorado, United States
McKee Medical Center
🇺🇸Loveland, Colorado, United States
Saint Mary's Hospital and Regional Medical Center
🇺🇸Grand Junction, Colorado, United States
Exempla Lutheran Medical Center
🇺🇸Wheat Ridge, Colorado, United States
Illinois CancerCare-Bloomington
🇺🇸Bloomington, Illinois, United States
Illinois CancerCare-Carthage
🇺🇸Carthage, Illinois, United States
Illinois CancerCare-Canton
🇺🇸Canton, Illinois, United States
Illinois CancerCare-Eureka
🇺🇸Eureka, Illinois, United States
Eureka Hospital
🇺🇸Eureka, Illinois, United States
Illinois CancerCare Galesburg
🇺🇸Galesburg, Illinois, United States
Illinois CancerCare-Kewanee Clinic
🇺🇸Kewanee, Illinois, United States
Mcdonough District Hospital
🇺🇸Macomb, Illinois, United States
Garneau, Stewart C MD (UIA Investigator)
🇺🇸Moline, Illinois, United States
Porubcin, Michael MD (UIA Investigator)
🇺🇸Moline, Illinois, United States
Stoffel, Thomas J MD (UIA Investigator)
🇺🇸Moline, Illinois, United States
Trinity Medical Center
🇺🇸Moline, Illinois, United States
Illinois CancerCare-Monmouth
🇺🇸Monmouth, Illinois, United States
Bromenn Regional Medical Center
🇺🇸Normal, Illinois, United States
Community Cancer Center Foundation
🇺🇸Normal, Illinois, United States
Proctor Hospital
🇺🇸Peoria, Illinois, United States
Pekin Hospital
🇺🇸Pekin, Illinois, United States
Pekin Cancer Treatment Center
🇺🇸Pekin, Illinois, United States
Illinois CancerCare-Pekin
🇺🇸Pekin, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸Peoria, Illinois, United States
Illinois Oncology Research Association CCOP
🇺🇸Peoria, Illinois, United States
Illinois Valley Hospital
🇺🇸Peru, Illinois, United States
McFarland Clinic
🇺🇸Ames, Iowa, United States
Perry Memorial Hospital
🇺🇸Princeton, Illinois, United States
Illinois CancerCare-Spring Valley
🇺🇸Spring Valley, Illinois, United States
Cedar Rapids Oncology Association
🇺🇸Cedar Rapids, Iowa, United States
Constantinou, Costas L MD (UIA Investigator)
🇺🇸Bettendorf, Iowa, United States
Mercy Hospital
🇺🇸Cedar Rapids, Iowa, United States
Oncology Associates at Mercy Medical Center
🇺🇸Cedar Rapids, Iowa, United States
Mercy Medical Center-Sioux City
🇺🇸Sioux City, Iowa, United States
Greater Baltimore Medical Center
🇺🇸Baltimore, Maryland, United States
Oakwood Hospital
🇺🇸Dearborn, Michigan, United States
Genesys Regional Medical Center-West Flint Campus
🇺🇸Flint, Michigan, United States
Sparrow Hospital
🇺🇸Lansing, Michigan, United States
Saint Mary Mercy Hospital
🇺🇸Livonia, Michigan, United States
Mercy Medical Center
🇺🇸Canton, Ohio, United States
Aultman Health Foundation
🇺🇸Canton, Ohio, United States
Virtua West Jersey Hospital Voorhees
🇺🇸Voorhees, New Jersey, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Southwest General Health Center Ireland Cancer Center
🇺🇸Middleburg Heights, Ohio, United States
UHHS-Westlake Medical Center
🇺🇸Westlake, Ohio, United States
Geisinger Medical Center-Cancer Center Hazelton
🇺🇸Hazleton, Pennsylvania, United States
Geisinger Medical Group
🇺🇸State College, Pennsylvania, United States
Geisinger Wyoming Valley
🇺🇸Wilkes-Barre, Pennsylvania, United States
Lankenau Hospital
🇺🇸Wynnewood, Pennsylvania, United States
Mainline Health CCOP
🇺🇸Wynnewood, Pennsylvania, United States
Graham Hospital Association
🇺🇸Canton, Illinois, United States
Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County
🇺🇸Mount Holly, New Jersey, United States
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
Dean Hematology and Oncology Clinic
🇺🇸Madison, Wisconsin, United States
Saint Mary's of Michigan
🇺🇸Saginaw, Michigan, United States
Ottawa Regional Hospital and Healthcare Center
🇺🇸Ottawa, Illinois, United States