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

NCT ID: NCT00976677

Last Updated: 2014-05-30

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-01-31

Study Completion Date

2013-11-30

Brief Summary

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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

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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.

Conditions

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Recurrent Non-small Cell Lung Cancer Stage IIIB Non-small Cell Lung Cancer Stage IV Non-small Cell Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

paclitaxel

Intervention Type DRUG

Given IV

carboplatin

Intervention Type DRUG

Given IV

bevacizumab

Intervention Type BIOLOGICAL

Given IV

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.

Group Type EXPERIMENTAL

erlotinib hydrochloride

Intervention Type DRUG

Given PO

paclitaxel

Intervention Type DRUG

Given IV

carboplatin

Intervention Type DRUG

Given IV

bevacizumab

Intervention Type BIOLOGICAL

Given IV

Interventions

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erlotinib hydrochloride

Given PO

Intervention Type DRUG

paclitaxel

Given IV

Intervention Type DRUG

carboplatin

Given IV

Intervention Type DRUG

bevacizumab

Given IV

Intervention Type BIOLOGICAL

Other Intervention Names

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CP-358,774 erlotinib OSI-774 Anzatax Asotax TAX Taxol Carboplat CBDCA JM-8 Paraplat Paraplatin anti-VEGF humanized monoclonal antibody anti-VEGF monoclonal antibody Avastin rhuMAb VEGF

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Corey Langer

Role: PRINCIPAL_INVESTIGATOR

Eastern Cooperative Oncology Group

Locations

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The Medical Center of Aurora

Aurora, Colorado, United States

Site Status

Boulder Community Hospital

Boulder, Colorado, United States

Site Status

Penrose-Saint Francis Healthcare

Colorado Springs, Colorado, United States

Site Status

Saint Anthony Central Hospital

Denver, Colorado, United States

Site Status

Porter Adventist Hospital

Denver, Colorado, United States

Site Status

Exempla Saint Joseph Hospital

Denver, Colorado, United States

Site Status

Presbyterian - Saint Lukes Medical Center - Health One

Denver, Colorado, United States

Site Status

Rose Medical Center

Denver, Colorado, United States

Site Status

Colorado Cancer Research Program CCOP

Denver, Colorado, United States

Site Status

Swedish Medical Center

Englewood, Colorado, United States

Site Status

Saint Mary's Hospital and Regional Medical Center

Grand Junction, Colorado, United States

Site Status

North Colorado Medical Center

Greeley, Colorado, United States

Site Status

Sky Ridge Medical Center

Lone Tree, Colorado, United States

Site Status

Longmont United Hospital

Longmont, Colorado, United States

Site Status

McKee Medical Center

Loveland, Colorado, United States

Site Status

Saint Mary Corwin Medical Center

Pueblo, Colorado, United States

Site Status

North Suburban Medical Center

Thornton, Colorado, United States

Site Status

Exempla Lutheran Medical Center

Wheat Ridge, Colorado, United States

Site Status

Saint Francis Hospital and Medical Center

Hartford, Connecticut, United States

Site Status

Illinois CancerCare-Bloomington

Bloomington, Illinois, United States

Site Status

Saint Joseph Medical Center

Bloomington, Illinois, United States

Site Status

Graham Hospital Association

Canton, Illinois, United States

Site Status

Illinois CancerCare-Canton

Canton, Illinois, United States

Site Status

Illinois CancerCare-Carthage

Carthage, Illinois, United States

Site Status

Memorial Hospital

Carthage, Illinois, United States

Site Status

Eureka Hospital

Eureka, Illinois, United States

Site Status

Illinois CancerCare-Eureka

Eureka, Illinois, United States

Site Status

Illinois CancerCare Galesburg

Galesburg, Illinois, United States

Site Status

Ingalls Memorial Hospital

Harvey, Illinois, United States

Site Status

Illinois CancerCare-Havana

Havana, Illinois, United States

Site Status

Mason District Hospital

Havana, Illinois, United States

Site Status

Illinois CancerCare-Kewanee Clinic

Kewanee, Illinois, United States

Site Status

Illinois CancerCare-Macomb

Macomb, Illinois, United States

Site Status

Mcdonough District Hospital

Macomb, Illinois, United States

Site Status

Garneau, Stewart C MD (UIA Investigator)

Moline, Illinois, United States

Site Status

Porubcin, Michael MD (UIA Investigator)

Moline, Illinois, United States

Site Status

Sharis, Christine M MD (UIA Investigator)

Moline, Illinois, United States

Site Status

Spector, David MD (UIA Investigator)

Moline, Illinois, United States

Site Status

Stoffel, Thomas J MD (UIA Investigator)

Moline, Illinois, United States

Site Status

Trinity Medical Center

Moline, Illinois, United States

Site Status

Illinois CancerCare-Monmouth

Monmouth, Illinois, United States

Site Status

Bromenn Regional Medical Center

Normal, Illinois, United States

Site Status

Community Cancer Center Foundation

Normal, Illinois, United States

Site Status

Illinois CancerCare-Community Cancer Center

Normal, Illinois, United States

Site Status

Illinois CancerCare-Ottawa Clinic

Ottawa, Illinois, United States

Site Status

Ottawa Regional Hospital and Healthcare Center

Ottawa, Illinois, United States

Site Status

Pekin Cancer Treatment Center

Pekin, Illinois, United States

Site Status

Pekin Hospital

Pekin, Illinois, United States

Site Status

Illinois CancerCare-Pekin

Pekin, Illinois, United States

Site Status

Methodist Medical Center of Illinois

Peoria, Illinois, United States

Site Status

Proctor Hospital

Peoria, Illinois, United States

Site Status

Illinois CancerCare-Peoria

Peoria, Illinois, United States

Site Status

Illinois Oncology Research Association CCOP

Peoria, Illinois, United States

Site Status

OSF Saint Francis Medical Center

Peoria, Illinois, United States

Site Status

Illinois CancerCare-Peru

Peru, Illinois, United States

Site Status

Illinois Valley Hospital

Peru, Illinois, United States

Site Status

Illinois CancerCare-Princeton

Princeton, Illinois, United States

Site Status

Perry Memorial Hospital

Princeton, Illinois, United States

Site Status

Illinois CancerCare-Spring Valley

Spring Valley, Illinois, United States

Site Status

McFarland Clinic

Ames, Iowa, United States

Site Status

Constantinou, Costas L MD (UIA Investigator)

Bettendorf, Iowa, United States

Site Status

Cedar Rapids Oncology Association

Cedar Rapids, Iowa, United States

Site Status

Mercy Hospital

Cedar Rapids, Iowa, United States

Site Status

Oncology Associates at Mercy Medical Center

Cedar Rapids, Iowa, United States

Site Status

Siouxland Hematology Oncology Associates

Sioux City, Iowa, United States

Site Status

Mercy Medical Center-Sioux City

Sioux City, Iowa, United States

Site Status

Saint Luke's Regional Medical Center

Sioux City, Iowa, United States

Site Status

Greater Baltimore Medical Center

Baltimore, Maryland, United States

Site Status

Saint Joseph Mercy Hospital

Ann Arbor, Michigan, United States

Site Status

Michigan Cancer Research Consortium Community Clinical Oncology Program

Ann Arbor, Michigan, United States

Site Status

Oakwood Hospital

Dearborn, Michigan, United States

Site Status

Saint John Hospital and Medical Center

Detroit, Michigan, United States

Site Status

Hurley Medical Center

Flint, Michigan, United States

Site Status

Genesys Regional Medical Center-West Flint Campus

Flint, Michigan, United States

Site Status

Allegiance Health

Jackson, Michigan, United States

Site Status

Sparrow Hospital

Lansing, Michigan, United States

Site Status

Saint Mary Mercy Hospital

Livonia, Michigan, United States

Site Status

Saint Joseph Mercy Oakland

Pontiac, Michigan, United States

Site Status

Saint Joseph Mercy Port Huron

Port Huron, Michigan, United States

Site Status

Saint Mary's of Michigan

Saginaw, Michigan, United States

Site Status

Saint John Macomb-Oakland Hospital

Warren, Michigan, United States

Site Status

Essentia Health Duluth Clinic CCOP

Duluth, Minnesota, United States

Site Status

Essentia Health Saint Mary's Medical Center

Duluth, Minnesota, United States

Site Status

Miller-Dwan Hospital

Duluth, Minnesota, United States

Site Status

Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County

Mount Holly, New Jersey, United States

Site Status

Newark Beth Israel Medical Center

Newark, New Jersey, United States

Site Status

Virtua West Jersey Hospital Voorhees

Voorhees Township, New Jersey, United States

Site Status

Mercy Medical Center

Canton, Ohio, United States

Site Status

Aultman Health Foundation

Canton, Ohio, United States

Site Status

Case Western Reserve University

Cleveland, Ohio, United States

Site Status

Lake University Ireland Cancer Center

Mentor, Ohio, United States

Site Status

Southwest General Health Center Ireland Cancer Center

Middleburg Heights, Ohio, United States

Site Status

UHHS-Chagrin Highlands Medical Center

Orange, Ohio, United States

Site Status

UHHS-Westlake Medical Center

Westlake, Ohio, United States

Site Status

Bryn Mawr Hospital

Bryn Mawr, Pennsylvania, United States

Site Status

Geisinger Medical Center

Danville, Pennsylvania, United States

Site Status

Geisinger Medical Center-Cancer Center Hazelton

Hazleton, Pennsylvania, United States

Site Status

Paoli Memorial Hospital

Paoli, Pennsylvania, United States

Site Status

Abramson Cancer Center of The University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Geisinger Medical Group

State College, Pennsylvania, United States

Site Status

Geisinger Wyoming Valley

Wilkes-Barre, Pennsylvania, United States

Site Status

Lankenau Hospital

Wynnewood, Pennsylvania, United States

Site Status

Mainline Health CCOP

Wynnewood, Pennsylvania, United States

Site Status

Parkland Memorial Hospital

Dallas, Texas, United States

Site Status

Zale Lipshy University Hospital

Dallas, Texas, United States

Site Status

Saint Paul Hospital

Dallas, Texas, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Dean Hematology and Oncology Clinic

Madison, Wisconsin, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2011-01967

Identifier Type: REGISTRY

Identifier Source: secondary_id

ECOG-E2508

Identifier Type: -

Identifier Source: secondary_id

CDR0000654212

Identifier Type: -

Identifier Source: secondary_id

E2508

Identifier Type: OTHER

Identifier Source: secondary_id

E2508

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA021115

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-01967

Identifier Type: -

Identifier Source: org_study_id