BAY 43-9006 (Sorafenib) to Treat Relapsed Non-Small Cell Lung Cancer
Condition: Non-Small-Cell Lung Carcinoma
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: BAY 43-9006 (Sorafenib)
Intervention description: Self administered oral doses at 400 mg twice a day with 250 ml (8 oz.) of water each morning and evening (i.e., 12-hourly) continuously in a 28 day cycle. Tablets may be taken with or without food.
Intervention MeSH terms: Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 37.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non-Small Cell; Molecular; Targeted; Therapies; Cancer; Non-Small Cell Lung Cancer; NSCLC

Summary:

      This study will investigate the effects and side effects of BAY 43-9006 in patients with
      advanced, recurrent, or refractory non-small cell lung cancer (NSCLC). BAY 43-9006 is one of
      a new class of anticancer agents known as bi-aryl ureas.

      Patients 18 years of age and older with NSCLC that has recurred or progressed after one
      regimen of chemotherapy may be eligible for this study. Candidates are screened with a
      medical history and physical examination; blood tests; tumor biopsy (see below); chest x-ray;
      electrocardiogram; and imaging studies, including positron emission tomography-computed
      tomography (PET-CT, see below) and dynamic, contrast-enhanced MRI (DCE-MRI, see below).

      Participants take BAY 43-9006 by mouth twice a day, morning and evening. On the first and
      15th days of treatment, patients are admitted to the hospital for pharmacokinetic studies;
      that is, a test of how the body handles the drug. For the test, blood is collected at
      intervals (at 15 minutes, 30 minutes, and 1, 2, 4, 6, 8, 12 and 24 hours after ingestion) to
      determine the drug's level in the bloodstream. Treatment with BAY 43-9006 continues until the
      study doctor determines that the medication is not beneficial or the patient wishes to
      withdraw from the study.

      In addition to drug therapy, patients undergo the following tests and procedures:

        -  Physical examination every 4 weeks

        -  Blood pressure checks once a week during the first 4 weeks

        -  Blood tests every week

        -  CT scans or other imaging tests, such as ultrasound or MRI, every 8 weeks to evaluate
           the tumor's response to treatment. CT is an x-ray test that provides detailed pictures
           of the inside of the body. It can be done from different angles, providing a
           3-dimensional picture of the part of the body being studied and allowing the doctor to
           see the location, nature, and extent of disease. MRI uses a powerful magnet and radio
           waves instead of x-rays to produce accurate, detailed pictures of organs and tissues.

        -  PET-CT approximately every 8 weeks to look at how different parts of the body take up
           and use glucose (a sugar nutrient). Because rapidly growing cells, such as tumors, use
           more sugar than normal cells do, this test can be used to detect cancer. For the test,
           the patient is given an injection of a sugar solution in which a radioactive tracer has
           been attached to the sugar molecule. A special camera detects the radiation emitted by
           the solution, and the resulting images show how much sugar is being used in various
           parts of the body. PET-CT uses the PET scan in combination with standard CT in a machine
           that does both tests.

        -  DCE-MRI after 2 weeks of treatment. This test uses MRI with a special non-radioactive
           dye to examine blood flow in a certain part of the body.

        -  Tumor biopsy (optional) after 2 weeks of treatment. A biopsy is the surgical removal of
           a small piece of tissue. The tumor biopsy is done either using a small bore needle under
           CT guidance or by direct visualization using a laparoscope/thoracoscope. For the needle
           biopsy, a needle is inserted through the skin and guided by CT into the tumor mass. For
           the laparoscopy/thoracoscopy, the patient is sedated or asleep and small lighted tubes
           are inserted into small holes made in the skin. The tumor is located and tissue
           withdrawn.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Histologically documented Non-small cell lung cancer and confirmed by the Laboratory of
        Pathology at the Clinical Center/National Institutes of Health (NIH) or the Laboratory of
        Pathology at National Naval Medical Center (NNMC).

        Recurrent or progressed Non-Small Cell Lung Cancer (NSCLC).

        Patients must have measurable disease, defined as at least one lesion that can be
        accurately measured in at least one dimension (longest diameter to be recorded) as greater
        than 20 mm with conventional techniques or as greater than 10 mm with spiral Computed
        tomography (CT) scan.

        Patients must have recovered from toxicity related to prior therapy to at least to grade 1
        (defined by Common Terminology Criteria for Adverse Events (CTCAE) 3.0) and must not have
        had prior chemotherapy within 4 weeks. Patients must be at least 28 days since any prior
        radiation or major surgery.

        Age greater than 18 years (males or non-pregnant females). Because no dosing or adverse
        event data are currently available on the use of BAY 43-9006 in patients less than 18 years
        of age, children are excluded from this study but will be eligible for future pediatric
        single-agent trials, if applicable.

        Life expectancy of greater than 3 months.

        Eastern Cooperative Oncology Group (ECOG) performance status less than 2 (Karnofsky > 60%).

        Patients must have adequate organ and marrow function (as defined below). Patients must
        have returned to base line or grade one from any acute toxicity related to prior therapy.

        Leukocytes greater than 3,000/micro l;

        Absolute neutrophil count greater than 1,200/micro l;

        Platelets greater than 100,000/micro l;

        International normalized ratio (INR) less than or equal to 1.2

        Partial thromboplastin time (PTT) less than or equal to 36 seconds or abnormality can be
        explained by the presences of lupus anticoagulant

        Total bilirubin less than or equal to 1.5 times the institutional upper limits of normal;

        Aspartate aminotransferase, oxaloacetic transaminase (AST,SGOT) and alanine transaminase,
        serum glutamic pyruvic transaminase (ALT,SGPT) less than 2.5 times the institutional upper
        limits of normal;

        Creatinine or creatinine clearance less than or equal to 1.5 times the institutional upper
        limits of normal or greater than 45 mL/min/1.73 m^2 for patients with creatinine levels
        above institutional normal.

        The effects of BAY 43-9006 on the developing human fetus at the recommended therapeutic
        dose are unknown. For this reason and because kinase inhibitors are known to be
        teratogenic, women of child-bearing potential and men must agree to use adequate
        contraception (hormonal or barrier method of birth control; abstinence) prior to study
        entry and for the duration of study participation and continue for at least 2 months after
        completion. Should a woman become pregnant or suspect she is pregnant while participating
        in this study, she should inform her treating physician immediately. Because there is an
        unknown but potential risk for adverse events in nursing infants secondary to treatment of
        the mother with BAY 43-9006, breastfeeding should be discontinued if the mother is treated
        with BAY 43-9006.

        Ability to comply with daily oral self administration schedule, and the ability to
        understand and the willingness to sign a written informed consent document.

        EXCLUSION CRITERIA:

        Patients with symptomatic brain metastases should be excluded from this clinical trial
        because of their poor prognosis and because they often develop progressive neurologic
        dysfunction that would confound the evaluation of neurologic and other adverse events.
        However, patients who have had treatment for their brain metastases and whose brain
        metastatic disease status has remained stable for at least 3 months without steroids may be
        enrolled at the discretion of the principal investigator.

        Uncontrolled medical illness including, but not limited to, ongoing or uncontrolled,
        symptomatic congestive heart failure (American Heart Association (AHA) Class II or worse),
        uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, or psychiatric
        illness/social situations that would limit compliance with study requirements.

        Human immunodeficiency virus (HIV)positive patients receiving combination anti-retroviral
        therapy are excluded from the study because of possible pharmacokinetic interactions with
        BAY 43-9006. HIV positive patients not receiving antiretroviral therapy are excluded due to
        the possibility that BAY 43-9006 may worsen their condition and the likelihood that the
        underlying condition may obscure the attribution of adverse events with respect to BAY
        43-9006.

        Patients may not be receiving any other investigational agents.

        History of another invasive malignancy in the last five years. Non-invasive, non-melanoma
        skin cancers will be allowed.

        Patients with conditions that would impair their ability to swallow tablets are excluded.

        Patients must not have any evidence of bleeding diathesis.

        Patients must not be on therapeutic anticoagulation. Prophylactic anticoagulation (i.e. low
        dose warfarin) of venous or arterial access devices is allowed provided that the
        requirements for prothrombin time (PT), international normalized ratio (INR) or partial
        thromboplastin time (PTT) are met.

        Both men and women and members of all races and ethnic groups are eligible for this trial.
        Every effort will be made to recruit women and minorities in this study.