Study of Low Dose Chemotherapy Plus Sorafenib as Initial Therapy for Patients With Advanced Non-Squamous Cell NSCLC
Condition: Non Squamous Cell Lung Cancer; Non Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Docetaxel + Sorafenib
Intervention description: Subjects will be treated with metronomic chemotherapy with low dose docetaxel weekly for 3 out of 4 weeks, and sorafenib will be administered continuously 400 mg bid on a 28 day cycle. Treatment with metronomic chemotherapy will be expressed as a 4-week cycle. Tumor response to treatment will be evaluated after every 8 weeks. Treatment with metronomic chemotherapy and sorafenib will continue for a total of 6 cycles unless there is evidence of disease progression, intolerable toxicity, or withdrawal of consent. Maintenance therapy with sorafenib will then continue until disease progression, intolerable toxicity or withdrawal of consent.
Intervention MeSH terms: Docetaxel; Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 19 Years
Healthy volunteers: No
Keywords: Docetaxel; Sorafenib

Summary:

      The purpose of this study is to assess the 2-month progression-free survival in patients with
      advanced or metastatic, non-squamous cell lung cancer treated with weekly low dose docetaxel
      in combination with a biologic dose of sorafenib.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pathologic-proven non-squamous cell-NSCLC

          -  Advanced non-squamous-NSCLC: Stage IIIB with pleural effusion or stage IV, or
             recurrent disease

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 2: In bed less than 50%
             of the time, unable to work, but able to care for self

          -  Measurable or non-measurable disease as defined by solid tumor response criteria
             (RECIST)

          -  No prior systemic chemotherapy or biologic therapy

          -  Age greater than or equal to 19 years old (Note: State of Alabama requirement)

          -  Adequate bone marrow and renal function as assessed by the following:

               -  Hemoglobin greater than or equal to 9.0 g/dL

               -  Absolute neutrophil count (ANC)greater than or equal to 1500/mm3

               -  Platelet count greater than or equal to 100,000/mm3

               -  Creatinine less than or equal to 1.5 times upper limit of normal (ULN)

          -  Hepatic function requirements

               -  Total bilirubin less than or equal to ULN

               -  AST and ALT and alkaline phosphatase must be within the range allowing for
                  eligibility. In determining eligibility the more abnormal of the two values (AST
                  and ALT) should be used

          -  Women of childbearing potential must have a negative serum pregnancy test performed
             within 72 hours prior to the start of treatment.

        Women of childbearing potential and men must agree to use adequate contraception (barrier
        method of birth control) prior to study entry and for the duration of study participation.

        Men should use adequate birth control for at least three months after the last
        administration of sorafenib.

          -  Ability to understand and the willingness to sign a written informed consent. A signed
             informed consent must be obtained prior to any study-specific procedures.

          -  International normalized ratio (INR) less than or equal to 1.5 or a prothrombin
             time/partial prothrombin time (PT/PTT) within normal limits. Patients receiving
             anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to
             participate. For patients on warfarin, the INR should be measured prior to initiation
             of sorafenib and monitored at least weekly, or as defined by the local standard of
             care, until INR is stable.

        Exclusion Criteria:

          -  Predominant squamous cell histology will be excluded

          -  Cardiac disease: Congestive heart failure greater than class II New York Heart
             Association (NYHA). Patents must not have unstable angina (anginal symptoms at rest)
             or new onset angina (began within the last 3 months) or myocardial infarction within
             the past 6 months.

          -  Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI
             of the brain to exclude brain metastasis.

          -  Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.

          -  Uncontrolled hypertension defined as systolic blood pressure >150 mmHg or diastolic
             pressure greater than 90 mmHg, despite optimal medical management.

          -  Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.

          -  Active clinically serious infection greater than Common Terminology Criteria for
             Adverse Events (CTCAE) Grade 2.

          -  Thrombotic or embolic events such as a cerebrovascular accident including transient
             ischemic attacks within the past 6 months.

          -  History of significant hemoptysis (defined as bright red blood of a ½ teaspoon or
             more). Patients with blood-tinged or blood-streaked sputum will be permitted on study
             if the hemoptysis amount to less than 5 mL of blood per episode and less than 10 mL of
             blood per 24 hour period.

          -  Any other hemorrhage/bleeding event greater than or equal to CTCAE Grade 3 within 4
             weeks of first dose of study drug.

          -  Serious non-healing wound, ulcer or bone fracture.

          -  Evidence or history of bleeding diathesis or coagulopathy.

          -  Major surgery, open biopsy or significant traumatic injury within 4 weeks of first
             study drug.

          -  Use of St. John's Wort or rifampin (rifampicin).

          -  Known or suspected allergy to sorafenib or any agent given in the course of this
             trial.

          -  Any condition that impairs patient's ability to swallow whole pills.

          -  Any malabsorption problem.

          -  History of severe hypersensitivity reaction to any drugs formulated with polysorbate
             80.

          -  Women who are breast-feeding.