Carboplatin, Paclitaxel, and Bevacizumab With or Without Erlotinib Hydrochloride in Treating Non-Smokers With Advanced Non-Small Cell Lung Cancer

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Recurrent Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer	Drug: erlotinib hydrochloride; Drug: paclitaxel; Drug: carboplatin; Biological: bevacizumab	Phase 2

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	10 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	Randomized Double-Blind Placebo Controlled Phase II Trial Evaluating Erlotinib in Non-Smoking Patients With (Bevacizumab-Eligible and Ineligible) Advanced Non-Small Cell Lung Cancer (NSCLC)
Study Start Date :	January 2010
Actual Primary Completion Date :	July 2012
Actual Study Completion Date :	November 2013

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: Arm I; 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.	Drug: paclitaxel; Given IV; Other Names: Anzatax; Asotax; TAX; Taxol Drug: carboplatin; Given IV; Other Names: Carboplat; CBDCA; JM-8; Paraplat; Paraplatin Biological: bevacizumab; Given IV; Other Names: anti-VEGF humanized monoclonal antibody; anti-VEGF monoclonal antibody; Avastin; rhuMAb VEGF
Experimental: 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.	Drug: erlotinib hydrochloride; Given PO; Other Names: CP-358,774; erlotinib; OSI-774 Drug: paclitaxel; Given IV; Other Names: Anzatax; Asotax; TAX; Taxol Drug: carboplatin; Given IV; Other Names: Carboplat; CBDCA; JM-8; Paraplat; Paraplatin Biological: bevacizumab; Given IV; Other Names: anti-VEGF humanized monoclonal antibody; anti-VEGF monoclonal antibody; Avastin; rhuMAb VEGF

Outcome Measures

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Primary Outcome Measures :

1. Progression-free Survival (PFS) [ Time Frame: 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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• 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)

Contacts and Locations

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Locations

United States, Colorado
The Medical Center of Aurora
Aurora, Colorado, United States, 80012
Boulder Community Hospital
Boulder, Colorado, United States, 80301
Penrose-Saint Francis Healthcare
Colorado Springs, Colorado, United States, 80907
Saint Anthony Central Hospital
Denver, Colorado, United States, 80204
Porter Adventist Hospital
Denver, Colorado, United States, 80210
Exempla Saint Joseph Hospital
Denver, Colorado, United States, 80218
Presbyterian - Saint Lukes Medical Center - Health One
Denver, Colorado, United States, 80218
Rose Medical Center
Denver, Colorado, United States, 80220
Colorado Cancer Research Program CCOP
Denver, Colorado, United States, 80224-2522
Swedish Medical Center
Englewood, Colorado, United States, 80110
Saint Mary's Hospital and Regional Medical Center
Grand Junction, Colorado, United States, 81502
North Colorado Medical Center
Greeley, Colorado, United States, 80631
Sky Ridge Medical Center
Lone Tree, Colorado, United States, 80124
Longmont United Hospital
Longmont, Colorado, United States, 80501
McKee Medical Center
Loveland, Colorado, United States, 80539
Saint Mary Corwin Medical Center
Pueblo, Colorado, United States, 81004
North Suburban Medical Center
Thornton, Colorado, United States, 80229
Exempla Lutheran Medical Center
Wheat Ridge, Colorado, United States, 80033
United States, Connecticut
Saint Francis Hospital and Medical Center
Hartford, Connecticut, United States, 06105
United States, Illinois
Illinois CancerCare-Bloomington
Bloomington, Illinois, United States, 61701
Saint Joseph Medical Center
Bloomington, Illinois, United States, 61701
Graham Hospital Association
Canton, Illinois, United States, 61520
Illinois CancerCare-Canton
Canton, Illinois, United States, 61520
Illinois CancerCare-Carthage
Carthage, Illinois, United States, 62321
Memorial Hospital
Carthage, Illinois, United States, 62321
Eureka Hospital
Eureka, Illinois, United States, 61530
Illinois CancerCare-Eureka
Eureka, Illinois, United States, 61530
Illinois CancerCare Galesburg
Galesburg, Illinois, United States, 61401
Ingalls Memorial Hospital
Harvey, Illinois, United States, 60426
Illinois CancerCare-Havana
Havana, Illinois, United States, 62644
Mason District Hospital
Havana, Illinois, United States, 62644
Illinois CancerCare-Kewanee Clinic
Kewanee, Illinois, United States, 61443
Illinois CancerCare-Macomb
Macomb, Illinois, United States, 61455
Mcdonough District Hospital
Macomb, Illinois, United States, 61455
Garneau, Stewart C MD (UIA Investigator)
Moline, Illinois, United States, 61265
Porubcin, Michael MD (UIA Investigator)
Moline, Illinois, United States, 61265
Sharis, Christine M MD (UIA Investigator)
Moline, Illinois, United States, 61265
Spector, David MD (UIA Investigator)
Moline, Illinois, United States, 61265
Stoffel, Thomas J MD (UIA Investigator)
Moline, Illinois, United States, 61265
Trinity Medical Center
Moline, Illinois, United States, 61265
Illinois CancerCare-Monmouth
Monmouth, Illinois, United States, 61462
Bromenn Regional Medical Center
Normal, Illinois, United States, 61761
Community Cancer Center Foundation
Normal, Illinois, United States, 61761
Illinois CancerCare-Community Cancer Center
Normal, Illinois, United States, 61761
Illinois CancerCare-Ottawa Clinic
Ottawa, Illinois, United States, 61350
Ottawa Regional Hospital and Healthcare Center
Ottawa, Illinois, United States, 61350
Pekin Cancer Treatment Center
Pekin, Illinois, United States, 61554
Pekin Hospital
Pekin, Illinois, United States, 61554
Illinois CancerCare-Pekin
Pekin, Illinois, United States, 61603
Methodist Medical Center of Illinois
Peoria, Illinois, United States, 61603
Proctor Hospital
Peoria, Illinois, United States, 61614
Illinois CancerCare-Peoria
Peoria, Illinois, United States, 61615
Illinois Oncology Research Association CCOP
Peoria, Illinois, United States, 61615
OSF Saint Francis Medical Center
Peoria, Illinois, United States, 61637
Illinois CancerCare-Peru
Peru, Illinois, United States, 61354
Illinois Valley Hospital
Peru, Illinois, United States, 61354
Illinois CancerCare-Princeton
Princeton, Illinois, United States, 61356
Perry Memorial Hospital
Princeton, Illinois, United States, 61356
Illinois CancerCare-Spring Valley
Spring Valley, Illinois, United States, 61362
United States, Iowa
McFarland Clinic
Ames, Iowa, United States, 50010
Constantinou, Costas L MD (UIA Investigator)
Bettendorf, Iowa, United States, 52722
Cedar Rapids Oncology Association
Cedar Rapids, Iowa, United States, 52403
Mercy Hospital
Cedar Rapids, Iowa, United States, 52403
Oncology Associates at Mercy Medical Center
Cedar Rapids, Iowa, United States, 52403
Siouxland Hematology Oncology Associates
Sioux City, Iowa, United States, 51101
Mercy Medical Center-Sioux City
Sioux City, Iowa, United States, 51104
Saint Luke's Regional Medical Center
Sioux City, Iowa, United States, 51104
United States, Maryland
Greater Baltimore Medical Center
Baltimore, Maryland, United States, 21204
United States, Michigan
Saint Joseph Mercy Hospital
Ann Arbor, Michigan, United States, 48106-0995
Michigan Cancer Research Consortium Community Clinical Oncology Program
Ann Arbor, Michigan, United States, 48106
Oakwood Hospital
Dearborn, Michigan, United States, 48124
Saint John Hospital and Medical Center
Detroit, Michigan, United States, 48236
Hurley Medical Center
Flint, Michigan, United States, 48502
Genesys Regional Medical Center-West Flint Campus
Flint, Michigan, United States, 48532
Allegiance Health
Jackson, Michigan, United States, 49201
Sparrow Hospital
Lansing, Michigan, United States, 48912
Saint Mary Mercy Hospital
Livonia, Michigan, United States, 48154
Saint Joseph Mercy Oakland
Pontiac, Michigan, United States, 48341-2985
Saint Joseph Mercy Port Huron
Port Huron, Michigan, United States, 48060
Saint Mary's of Michigan
Saginaw, Michigan, United States, 48601
Saint John Macomb-Oakland Hospital
Warren, Michigan, United States, 48093
United States, Minnesota
Essentia Health Duluth Clinic CCOP
Duluth, Minnesota, United States, 55805
Essentia Health Saint Mary's Medical Center
Duluth, Minnesota, United States, 55805
Miller-Dwan Hospital
Duluth, Minnesota, United States, 55805
United States, New Jersey
Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County
Mount Holly, New Jersey, United States, 08060
Newark Beth Israel Medical Center
Newark, New Jersey, United States, 07112
Virtua West Jersey Hospital Voorhees
Voorhees, New Jersey, United States, 08043
United States, Ohio
Mercy Medical Center
Canton, Ohio, United States, 44708
Aultman Health Foundation
Canton, Ohio, United States, 44710
Case Western Reserve University
Cleveland, Ohio, United States, 44106
Lake University Ireland Cancer Center
Mentor, Ohio, United States, 44060
Southwest General Health Center Ireland Cancer Center
Middleburg Heights, Ohio, United States, 44130
UHHS-Chagrin Highlands Medical Center
Orange Village, Ohio, United States, 44122
UHHS-Westlake Medical Center
Westlake, Ohio, United States, 44145
United States, Pennsylvania
Bryn Mawr Hospital
Bryn Mawr, Pennsylvania, United States, 19010
Geisinger Medical Center
Danville, Pennsylvania, United States, 17822-2001
Geisinger Medical Center-Cancer Center Hazelton
Hazleton, Pennsylvania, United States, 18201
Paoli Memorial Hospital
Paoli, Pennsylvania, United States, 19301
Abramson Cancer Center of The University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Geisinger Medical Group
State College, Pennsylvania, United States, 16801
Geisinger Wyoming Valley
Wilkes-Barre, Pennsylvania, United States, 18711
Lankenau Hospital
Wynnewood, Pennsylvania, United States, 19096
Mainline Health CCOP
Wynnewood, Pennsylvania, United States, 19096
United States, Texas
Parkland Memorial Hospital
Dallas, Texas, United States, 75235
Zale Lipshy University Hospital
Dallas, Texas, United States, 75235
Saint Paul Hospital
Dallas, Texas, United States, 75390
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
United States, Wisconsin
Dean Hematology and Oncology Clinic
Madison, Wisconsin, United States, 53717

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Principal Investigator:	Corey Langer	Eastern Cooperative Oncology Group

More Information

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Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00976677 History of Changes
Other Study ID Numbers:	NCI-2011-01967; NCI-2011-01967 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); ECOG-E2508; CDR0000654212; E2508 ( Other Identifier: Eastern Cooperative Oncology Group ); E2508 ( Other Identifier: CTEP ); U10CA021115 ( U.S. NIH Grant/Contract )
First Posted:	September 14, 2009
Results First Posted:	July 22, 2013
Last Update Posted:	May 30, 2014
Last Verified:	December 2013

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Paclitaxel; Albumin-Bound Paclitaxel; Bevacizumab; Carboplatin; Erlotinib Hydrochloride	Antibodies; Immunoglobulins; Antibodies, Monoclonal; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Immunologic Factors