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Clinical Trials (PDQ®)

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

Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIBiomarker/Laboratory analysis, TreatmentActive18 and overOtherRC1126
NCI-2012-00053, NCT01532089

Trial Description

Summary

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.

Further Study Information

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 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

Trial Contact Information

Trial Lead Organizations/Sponsors

Academic and Community Cancer Research United

Thomas Stinchcombe, M.D.Study Chair

Trial Sites

U.S.A.
Illinois
  Peoria
 Illinois Cancer Care, PC
 Nancy J Williams Ph: 309-243-3614
  Email: nwilliams@illinoiscancercare.com
 Sachdev P Thomas, MDPrincipal Investigator
  Urbana
 Carle Cancer Center at Carle Foundation Hospital
 Carle Cancer Center Research Ph: 217-383-3516
  Email: Cancer.Resaerch@Carle.com
 James R. Egner, M.D.Principal Investigator
Michigan
  Grand Rapids
 Grand Rapids Clinical Oncology Program
 Connie Szczepanek, RN, BSN Ph: 616-391-1230
  Email: grcop-regulatory@grcop.org
 Gilbert DA Padula, M.D.Principal Investigator
Minnesota
  Rochester
 Academic and Community Cancer Research United
 Thomas E. Stinchcombe Ph: 919-966-9268
  Email: thomas_stinchcombe@med.unc.edu
 Thomas E. Stinchcombe, MDPrincipal Investigator
  St. Cloud
 Coborn Cancer Center / CentraCare Clinic
 Stacy Veches, RN, BSN Ph: 320-229-5199 Ext.70826
  Email: vechess@centracare.com
 Donald J Jurgens, MDPrincipal Investigator
New Hampshire
  Hooksett
 NH Oncology - Hematology, PA
 NHOH Clinical Trial Office Ph: 603-232-8908
 Douglas Jay WecksteinPrincipal Investigator
North Carolina
  Chapel Hill
 Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
 Sara M. Gulino, MS, CCRP Ph: 919-966-4432 Ext.243
  Email: gse52@med.unc.edu
 Thomas E. Stinchcombe, MDPrincipal Investigator
  Durham
 Duke Cancer Institute
 Jeffrey Crawford, M.D. Ph: 919-681-9509
  Email: craw006@mc.duke.edu
 Jeffrey Crawford, M.D.Principal Investigator
North Dakota
  Fargo
 Sanford Health / Roger Maris Cancer Center
 Amber Leach Ph: 701-234-5899
 Preston D. Steen, M.D.Principal Investigator
Ohio
  Columbus
 Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
 Ben T Shoemaker, BS Ph: 614-366-6413
  Email: ben.shoemaker@osumc.edu
 Gregory A. OttersonPrincipal Investigator
  Dayton
 CCOP - Dayton
 Cara M Nolan Ph: 937-775-1354
  Email: cara.nolan@wright.edu
 Howard M. GrossPrincipal Investigator
South Carolina
  Spartanburg
 Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
 Bunny B. McKnown, RN Ph: 864-560-6812
  Email: bmcknown@srhs.com
 James Dewitt BeardenPrincipal Investigator
South Dakota
  Rapid City
 Regional Cancer Care Institute
 Amy Boylan, RN Ph: 605-719-2325
  Email: aboylan1@regionalhealth.com
 Richard C Tenglin, MDPrincipal Investigator
  Sioux Falls
 Sanford Cancer Center at Sanford USD Medical Center
 Janet Wernisch, RN Ph: 605-328-1368
 Miroslaw A. MazurczakPrincipal Investigator
Wisconsin
  Green Bay
 St. Vincent Hospital Regional Cancer Center
 Jolene Cheslock, MS Ph: 920-433-8272
  Email: jolene.cheslock@stvgb.org
 Anthony Jaslowski, MDPrincipal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01532089
ClinicalTrials.gov processed this data on July 22, 2014

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.

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