BATTLE Program: Sorafenib in Patients With NSCLC
Condition: Lung Cancer
MeSH terms: Lung Neoplasms
Intervention: Sorafenib
Intervention description: 400 mg By Mouth Twice Daily for 28 Days.
Intervention MeSH terms: Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 105.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lung Cancer; Non-Small Cell Lung Cancer; NSCLC; Sorafenib; BAY 43-9006; Battle Program

Summary:

      Primary Objective:

        -  To determine the 8 week progression-free survival rate (i.e. disease control rate) in
           patients with advanced non-small cell lung cancer (NSCLC) who have failed at least one
           prior chemotherapy regimen.

      Secondary Objective:

      The secondary objectives of this study will be to:

        -  Determine the overall response rate

        -  Determine the overall survival

        -  Determine the time to disease progression

        -  Assess the safety/toxicity of the study treatment

        -  Assess biomarker modulation in the tumor tissue and serum samples from the treatment.

        -  Assess plasma and intra-tumor concentrations of study treatment
    

Eligibility criteria:

        Inclusion Criteria:

          1. The patient has a diagnosis of pathologically confirmed NSCLC by tumor biopsy and/or
             fine-needle aspiration.

          2. The patient has a diagnosis of either stage IIIB, stage IV, or advanced, incurable
             NSCLC, and failed at least one front-line metastatic NSCLC chemotherapy regimen.
             (Patients who have failed adjuvant or locally advanced therapy within 6 months are
             also eligible to participate in study).

          3. The patient has uni-dimensionally measurable NSCLC.

          4. Karnofsky performance status >/= 60 or ECOG performance status 0-2

          5. The patient has biopsy accessible tumor.

          6. The patient has adequate hematologic function as defined by an absolute neutrophil
             count (ANC) >/= 1,500/mm^3, platelet count >/= 100,000/mm^3, white blood count (WBC)
             >/= 3,000/ mm^3, and hemoglobin >/= 9 g/dL.

          7. The patient has adequate hepatic function as defined by a total bilirubin level </=
             1.5 * the upper limit of normal, and alkaline phosphatase, AST or ALT </= 2.5 * the
             upper limit of normal.

          8. The patient has adequate renal function as defined by a serum creatinine level </= 1.5
             mg/dL or a calculated creatinine clearance of >/= 60cc/minute.

          9. The patient has Prothrombin time (PT) < 1.5 * upper limit of normal

         10. If patient has brain metastasis, they must have been stable (treated or asymptomatic)
             for at least 4 weeks after radiation if treated with radiation and not have used
             steroids for at least 1 week. Re-imaging performed after 2 weeks, upon completion of
             radiation therapy.

         11. The patient is >/= 18 years of age.

         12. The patient has signed informed consent.

         13. The patient is eligible if disease free from a previously treated malignancy, other
             than a previous NSCLC, for greater than two years. Patients with a history of prior
             basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix are exempt
             from exclusion.

         14. Women of childbearing potential 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.Childbearing potential will be defined as women who have had
             menses within the past 12 months,who have not had tubal ligation or bilateral
             oophorectomy.Should a woman become pregnant or suspect that she is pregnant while
             participating in this study,she should inform her treating physician immediately.The
             patient,if a man,agrees to use effective contraception or abstinence.

         15. Subject must be considered legally capable of providing his or her own consent for
             participation in this study.

        Exclusion Criteria:

          1. The patient has received prior investigational therapy, chemotherapy, surgery, or
             radiotherapy within 4 weeks of initiating study drug

          2. The patient has undergone prior thoracic or abdominal surgery within 28 days of study
             entry, excluding prior diagnostic biopsy.

          3. The patient has received radiation therapy to the measurable tumor within 6 months.
             Patients are allowed to have local irradiation for the management of tumor-related
             symptoms (bones, brain). However, if a patient has active new disease growing in the
             previously irradiated site, the patient will be eligible to participate in the study.

          4. The patient has a significant medical history or unstable medical condition (unstable
             systemic disease: congestive heart failure (New York Heart Association Functional
             Classification class II or worse), recent myocardial infarction within 3 months,
             unstable angina, active infection (i.e. currently treated with antibiotics),
             uncontrolled hypertension). Patients with controlled diabetes will be allowed. Patient
             must be able to undergo procedure for tissue acquisition.

          5. The patient has uncontrolled seizure disorder, active neurologic disease, or
             neuropathy >/= grade 2. Patients with meningeal or central nervous System (CNS)
             involvement by tumor are eligible for the study if the above exclusion criteria are
             not met.

          6. The patient is pregnant (confirmed by serum b-HCG if applicable) or is breastfeeding.

          7. Any condition that is unstable or could jeopardize the safety of the patient and its
             compliance in the study, in the investigator's judgment.

          8. The patient is actively taking herbal remedies or over-the-counter biologics (e.g.,
             shark cartilage, high dose antioxidants).

          9. Patients will be allowed to have prior biologic (i.e. Vascular endothelial growth
             factor (VEGF), epidermal growth factor family (EGFR), etc.) therapy. However, the
             patient will be excluded from a given study if he/she has received the same therapy as
             the clinical trial (i.e. If a patient has been previously treated with bevacizumab,
             they are allowed to enroll in any of the 4 studies. If a patient has been previously
             treated with erlotinib, they are excluded from the clinical trials with erlotinib). In
             addition, if a patient has been previously treated with gefitinib (Iressa), they are
             excluded from the clinical trials with erlotinib.

         10. Prior hemoptysis or bleeding diathesis.

         11. Hypertension not controlled by medical therapy (systolic blood pressure greater than
             160 mm Hg or diastolic blood pressure greater than 100 mm Hg)

         12. Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B
             or C.

         13. History of seizure disorder requiring medication (such as steroids or
             anti-epileptics).

         14. History of organ allograft and bone marrow transplant

         15. Previous malignancy (except for cervical carcinoma in situ, adequately treated basal
             cell carcinoma, or superficial bladder tumors [Ta, Tis & T1] or other malignancies
             curatively treated > 3 years prior to entry).

         16. Patients with clinically significant bleeding (e.g., gastrointestinal bleeding) within
             the past month prior to study entry are ineligible.

         17. Pregnant or breast-feeding patients. Women of childbearing potential must have a
             negative pregnancy test performed within 48 hours of the start of treatment. Both men
             and women enrolled in this trial must use adequate barrier birth control measures
             (e.g., cervical cap, condom, and diaphragm) during the course of the trial. Oral birth
             control methods alone will not be considered adequate on this study, because of the
             potential pharmacokinetic interaction between BAY 43-9006 and oral contraceptives.

         18. Substance abuse, medical, psychological or social conditions that, in the judgment of
             the investigator, is likely to interfere with the patient's participation in the study
             or evaluation of the study results.

         19. Known allergy to the investigational agent or any agent given in association with this
             trial.

         20. Concurrent use of St. John's Wort, Rifampicin, and/or ritonavir.