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

Overview

  • Study type

    Interventional
  • Study phase

    II
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Rochester, Minnesota: 11-006881
    NCT ID: NCT01532089
    Sponsor Protocol Number: RC1126

About this study

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See 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

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Julian Molina, M.D., Ph.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

.
CLS-20115807

Mayo Clinic Footer