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Erlotinib With or Without Bevacizumab in Treating Patients With Stage IV Non-Small Cell Lung Cancer With EGFR Mutations

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Academic and Community Cancer Research United
Sponsor:
Information provided by (Responsible Party):
Academic and Community Cancer Research United
ClinicalTrials.gov Identifier:
NCT01532089
First received: February 7, 2012
Last updated: July 22, 2014
Last verified: July 2014
  Purpose

This randomized phase II trial studies how well giving erlotinib (Tarceva) with or without bevacizumab (Avastin) works in treating patients with stage IV non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Bevacizumab blocks the ability of tumors to grow new blood vessels and spread. It is not yet known whether erlotinib is more effective when given alone or with bevacizumab.


Condition Intervention Phase
Stage IV Non-small Cell Lung Cancer
Drug: erlotinib
Biological: bevacizumab
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Erlotinib Alone or In Combination With Bevacizumab in Patients With Non-Small Cell Lung Cancer and Activating Epidermal Growth Factor Receptor Mutations

Resource links provided by NLM:


Further study details as provided by Academic and Community Cancer Research United:

Primary Outcome Measures:
  • Progression free survival (PFS) of erlotinib and bevacizumab versus that of erlotinib alone in untreated advanced non-small cell lung cancer patients who have activating EGFR mutations [ Time Frame: From the date of randomization to the date of disease progression or death of any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    Described graphically using the Kaplan and Meier product limit estimator. Comparisons of PFS between arms will be conducted using a stratified log rank test. Cox proportional hazards model will be used to estimate the adjusted hazard ratios and their 95% confidence intervals. Hazard ratio for treatment effect will be estimated for each subgroup of patients that has significant interaction with treatment. The robustness of treatment effects in different patient subgroups will examined in Forest plots.


Secondary Outcome Measures:
  • Overall survival of erlotinib and bevacizumab versus erlotinib alone [ Time Frame: Time from randomization to death of any causes assessed up to 5 years ] [ Designated as safety issue: No ]
  • Response rate (complete or partial) to each treatment [ Time Frame: Baseline, every 6 weeks for 18 months, then every 3 months ] [ Designated as safety issue: No ]
  • Progression free survival of patients with different mutation types (exon deletion 19 vs. exon 21 L858R) [ Time Frame: From the date of randomization to the date of disease progression or death of any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
  • Types and the frequency of treatment-related adverse events for erlotinib and bevacizumab and erlotinib alone [ Time Frame: Prior to each course and 21-42 days after treatment discontinuation ] [ Designated as safety issue: Yes ]
  • Correlation of EGFR mutations detected in plasma DNA with those detected in tumor DNA [ Time Frame: Baseline, during each radiographic assessment and at the time of progression ] [ Designated as safety issue: No ]
  • Prevalence of EGFR T790M resistance mutations from pretreatment tumor biopsies using more sensitive mutation detection methods [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Effect of EGFR T790M on progression free survival [ Time Frame: Baseline, up to 5 years ] [ Designated as safety issue: No ]
  • Predictive value of plasma VEGF-A levels on progression free survival in patients treated with erlotinib alone or in combination with bevacizumab [ Time Frame: Baseline ] [ Designated as safety issue: No ]

Estimated Enrollment: 118
Study Start Date: March 2012
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A (enzyme inhibitor)
Patients receive erlotinib PO QD on days 1-21.
Drug: erlotinib
Given PO
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm B (enzyme inhibitor, monoclonal antibody)
Patients receive erlotinib as in Arm A and bevacizumab IV over 30-90 minutes on day 1.
Drug: erlotinib
Given PO
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES: I. To determine the progression-free survival of erlotinib (erlotinib) and bevacizumab versus that of erlotinib alone for the purpose of deciding if the combination arm is worth pursuing in a phase III trial. SECONDARY OBJECTIVES: I. To investigate the overall survival of erlotinib and bevacizumab versus erlotinib alone. II. To investigate the response rate of erlotinib and bevacizumab versus erlotinib alone. III. To investigate the progression-free survival in patients with exon deletion 19 or exon 21 L858R EGFR point mutations. IV. To investigate the toxicity of erlotinib and bevacizumab versus erlotinib alone using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. TERTIARY OBJECTIVES: I. To correlate EGFR mutations detected in plasma deoxyribonucleic acid (DNA) with those detected in tumor DNA. II. To estimate the prevalence of EGFR T790M resistance mutations from pretreatment tumor biopsies using more sensitive mutation detection methods. III. To investigate progression free survival of EGFR mutant NSCLC patients with and without concurrent EGFR T790M detected from pre-treatment tumor specimen using allele specific quantitative polymerase chain reaction (PCR). IV. To prospectively evaluate the predictive value of plasma vascular endothelial growth factor A (VEGF-A) levels on progression free survival in patients treated with erlotinib alone or in combination with bevacizumab. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive erlotinib orally (PO) once daily (QD) on days 1-21. ARM B: Patients receive erlotinib as in Arm A and bevacizumab intravenously (IV) over 30-90 minutes on day 1. In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically for up to 5 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologic documentation of primary lung carcinoma, non-squamous histology with activating epidermal growth factor receptor (defined as deletion 19 or exon 21 L858R mutation) *Note: EGFR mutation testing must be performed at a Clinical Laboratory Improvement Amendments (CLIA) certified lab; either institutional or through a commercial laboratory (e.g. Genzyme, Response Genetics, etc); the laboratory report from the commercial laboratories report the specific mutations detected, and the method of detecting the exon 19 and exon 21 L858R point mutations must be available
  • Stage IV disease according to the 7th Edition of the American Joint Committee on Cancer staging system -Measureable disease- Life expectancy of >= 12 months
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
  • Absolute neutrophil count (ANC) >= 1, 500/mm^3
  • Platelet count >= 100,000/mm^3
  • Hemoglobin >= 9.0 g/dL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x ULN in patients without liver or bone metastases; < 5 x ULN in patients with liver or bone metastases
  • Cockcroft-Gault calculated creatinine clearance of >= 45 ml/min or creatinine =< 1.5 x ULN
  • Prothrombin time (PT) =< 1.5 x ULN
  • Partial thromboplastin time (PTT) =< ULN
  • Urine dipstick proteinuria < 2+ * Note: Patients discovered to have >= 2 + proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate < 1 g of protein in 24 hours
  • Negative pregnancy test done =< 7 days prior to randomization, for women of childbearing potential only
  • Provide informed written consent
  • Willing to return to Alberta Cooperative Conservation Research Unit (ACCRU) enrolling institution for follow-up
  • Willing to provide tissue and blood samples for correlative research purposes

Exclusion Criteria:

  • Mixed, non-small cell and small cell tumors or mixed adenosquamous carcinomas with a predominant squamous component
  • Prior chemotherapy or treatment for metastatic non-small cell lung cancer Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown * Pregnant women * Nursing women * Men or women of childbearing potential who are unwilling to employ adequate contraception Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive, per MD discretion
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • Other active malignancy =< 3 years prior to randomization; EXCEPTIONS: Non melanotic skin cancer or carcinoma-in-situ of the cervix * Note: If there is a history of prior malignancy, they must not be receiving other specific treatment (i.e. hormonal therapy) for their cancer
  • History of myocardial infarction or other evidence of arterial thrombotic disease (angina) * Note: Allowed only if patient has no evidence of active disease for at least 6 months prior to randomization
  • History of cerebral vascular accident (CVA) or transient ischemic attack (TIA) =< 6 months prior to randomization
  • Ongoing or active infection, symptomatic congestive heart failure (New York Heart Association >= grade 2), cardiac arrhythmia, psychiatric illness/social situations, or any other medical condition that would limit compliance with study requirements
  • History of bleeding diathesis or coagulopathy
  • Inadequately controlled hypertension (systolic blood pressure of > 150 mmHg or diastolic pressure > 100 mmHg on anti-hypertensive medications) * Note: History of hypertensive crisis or hypertensive encephalopathy not allowed
  • Current or recent (=< 10 days prior to randomization use of aspirin (> 325 mg/day), clopidogrel (> 75 mg/day), or current or recent (=< 10 days prior to randomization use of full- dose (i.e. therapeutic dose) oral or parenteral anticoagulants or thrombolytic agent for therapeutic purposes * Note: Prophylactic use of anticoagulants is allowed
  • Serious non-healing wound, ulcer, bone fracture, or have undergone a major surgical procedure, open biopsy, or significant traumatic injury =< 28 days or core biopsy =< 7 days prior to randomization
  • History of abdominal fistula, gastrointestinal perforation, or intrabdominal abscess =< 6 months prior to randomization
  • Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • History of hemoptysis >= grade 2 (defined as bright red blood of at least 2.5 mL) =< 3 months prior to randomization
  • Known central nervous system (CNS) disease, except for treated brain metastasis * Note: Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, for at least 7 days as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT]) during the screening period; anticonvulsants (stable dose) are allowed; treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, linear accelerator [LINAC], or equivalent) or a combination as deemed appropriate by the treating physician; patients with CNS metastases treated by neurosurgical resection or brain biopsy performed =< 3 months prior to randomization will be excluded
  • Significant vascular disease (e.g. aortic aneurysm surgical repair or recent peripheral arterial thrombosis) =< 6 months prior to randomization Radiotherapy to any site for any reason =< 28 days prior to randomization *Note: Palliative radiotherapy to bone lesions and WBRT > 14 days prior to randomization is allowed
  • Receiving any medications or substances that are strong or moderate inhibitors of cytochrome P450 3A4 (CYP3A4) are prohibited =< 7 days prior to registration
  • Receiving any medications or substances that are inducers of CYP3A4 use of inducers are prohibited =< 7 days prior to registration
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01532089

Locations
United States, Illinois
University of Chicago Medical Center Not yet recruiting
Chicago, Illinois, United States, 60637
Contact: Heather M Hungerford    773-702-9251    hhunger@bsd.uchicago.edu   
Principal Investigator: Victoria M Villaflor, MD         
Illinois Cancer Care, PC Recruiting
Peoria, Illinois, United States, 61615
Contact: Nancy J Williams    309-243-3614    nwilliams@illinoiscancercare.com   
Principal Investigator: Sachdev P Thomas, MD         
Carle Cancer Center Recruiting
Urbana, Illinois, United States, 61801
Contact: Carle Cancer Center Research    217-383-3516    Cancer.Resaerch@Carle.com   
Principal Investigator: James R. Egner, M.D.         
United States, Michigan
Grand Rapids Clinical Oncology Program Recruiting
Grand Rapids, Michigan, United States, 49503
Contact: Connie Szczepanek, RN, BSN    616-391-1230    grcop-regulatory@grcop.org   
Principal Investigator: Gilbert DA Padula, M.D.         
United States, Minnesota
Academic and Community Cancer Research United Recruiting
Rochester, Minnesota, United States, 55905
Contact: Thomas E. Stinchcombe    919-966-9268    thomas_stinchcombe@med.unc.edu   
Principal Investigator: Thomas E. Stinchcombe, MD         
Mayo Clinic Active, not recruiting
Rochester, Minnesota, United States, 55905
Coborn Cancer Center / CentraCare Clinic Recruiting
St. Cloud, Minnesota, United States, 56303
Contact: Stacy Veches, RN, BSN    320-229-5199 ext 70826    vechess@centracare.com   
Principal Investigator: Donald J Jurgens, MD         
United States, New Hampshire
NH Oncology - Hematology, PA Recruiting
Hooksett, New Hampshire, United States, 03106
Contact: NHOH Clinical Trial Office    603-232-8908      
Principal Investigator: Douglas J Weckstein, MD         
United States, North Carolina
University of North Carolina at Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Sara M. Gulino, MS, CCRP    919-966-4432 ext 243    gse52@med.unc.edu   
Principal Investigator: Thomas E. Stinchcombe, MD         
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Jeffrey Crawford, M.D.    919-681-9509    craw006@mc.duke.edu   
Principal Investigator: Jeffrey Crawford, M.D.         
United States, North Dakota
Sanford Health / Roger Maris Cancer Center Recruiting
Fargo, North Dakota, United States, 58103
Contact: Amber Leach    701-234-5899      
Principal Investigator: Preston D. Steen, M.D.         
United States, Ohio
James Cancer Hospital/Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Ben T Shoemaker, BS    614-366-6413    ben.shoemaker@osumc.edu   
Principal Investigator: Gregory A Otterson, MD         
Dayton Clinical Oncology Program Recruiting
Dayton, Ohio, United States, 45420
Contact: Cara M Nolan    937-775-1354    cara.nolan@wright.edu   
Principal Investigator: Howard M Gross, MD         
United States, South Carolina
Spartanburg Regional Medical Center Recruiting
Spartanburg, South Carolina, United States, 29303
Contact: Bunny B. McKnown, RN    864-560-6812    bmcknown@srhs.com   
Principal Investigator: James D. Bearden, III, MD         
United States, South Dakota
Regional Cancer Care Institute Recruiting
Rapid City, South Dakota, United States, 57701
Contact: Amy Boylan, RN    605-719-2325    aboylan1@regionalhealth.com   
Principal Investigator: Richard C Tenglin, MD         
Sanford Cancer Center Oncology Clinic Recruiting
Sioux Falls, South Dakota, United States, 57104
Contact: Janet Wernisch, RN    605-328-1368      
Principal Investigator: Miroslaw Mazurczak, M.D.         
United States, Wisconsin
St. Vincent Hospital Recruiting
Green Bay, Wisconsin, United States, 54301
Contact: Jolene Cheslock, MS    920-433-8272    jolene.cheslock@stvgb.org   
Principal Investigator: Anthony Jaslowski, MD         
Sponsors and Collaborators
Academic and Community Cancer Research United
Investigators
Study Chair: Thomas Stinchcombe, M.D. Academic and Community Cancer Research United
  More Information

No publications provided

Responsible Party: Academic and Community Cancer Research United
ClinicalTrials.gov Identifier: NCT01532089     History of Changes
Other Study ID Numbers: RC1126, NCI-2012-00053
Study First Received: February 7, 2012
Last Updated: July 22, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Antibodies
Antibodies, Monoclonal
Bevacizumab
Enzyme Inhibitors
Erlotinib
Immunoglobulins
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014