A Safety and Efficacy Study of Carboplatin, Paclitaxel, Bevacizumab and CA4P in Non-Small Cell Lung Cancer
Condition: Tumors
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Fosbretabulin; Carboplatin; Paclitaxel; Bevacizumab
Intervention description: Arm 2 only: Fosbretabulin (60 mg/m2) on Days 7,14 and 21 for 6 cycles.; Chemotherapy: Carboplatin (AUC 6) on Day 1 of each 21 day cycle for 6 cycles.; Chemotherapy: Paclitaxel (20 mg/m2) on Day 1 of each 21-day cycle for 6 cycles.; Bevacizumab (15 mg/kg) on Day 1 of each 21-day cycle for 6 cycles.
Intervention MeSH terms: Paclitaxel; Fosbretabulin; Combretastatin; Bevacizumab; Carboplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 63.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: non-small cell lung cancer; non-small cell lung carcinoma; neoplasms, lung; lung cancer; tumors; NSCLC

Summary:

      The purpose of this study is to determine the safety, tolerability and efficacy of
      combretastatin A4 phosphate (CA4P), also known as fosbretabulin, in combination with
      bevacizumab (Avastin), carboplatin and paclitaxel in patients with chemotherapy naïve
      non-small cell lung cancer (NSCLC). This is a randomized parallel arm study. All participants
      will receive carboplatin, paclitaxel and bevacizumab, and half will additionally receive
      CA4P. Patients who complete the first 6 cycles of therapy and have not experienced disease
      progression will receive maintenance therapy with bevacizumab alone or with bevacizumab plus
      CA4P.

      The rationale for this study is the potential additive or synergistic actions of vascular
      disrupting agents like CA4P with anti-angiogenic agents like bevacizumab.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pathologically confirmed Stage IIIB NSCLC with malignant pleural effusion, or Stage IV
             disease

          -  Measurable disease on CT scan (by the Response Evaluation Criteria in Solid Tumors
             [RECIST] criteria)

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1 (which
             means able to independently care for self and to perform light work) .

          -  Adequate blood counts

          -  Adequate liver and kidney function

          -  Subjects or their legal representatives must be able to read, understand and provide
             written informed consent to participate in the trial.

        Exclusion Criteria:

          -  Predominant Squamous Cell NSCLC histology.

          -  History of treatment for NSCLC with chemotherapy, biological therapy, immunotherapy
             (surgery or radiation therapy are accepted)

          -  Brain (CNS) metastasis by head CT scan or MRI

          -  Subjects with history of prior malignancy except for curatively treated basal cell
             carcinoma of the skin; cervical intra-epithelial neoplasia; or localized prostate
             cancer with a current prostate specific antigen (PSA) of < 4.0 mg/dL. Subjects with
             other curatively treated malignancies who have no evidence of metastatic disease and
             >2 year disease free interval may be entered after discussion with the Medical
             Monitor.

          -  History of bleeding disorders, particularly coughing up ≥ ½ teaspoon bright red blood
             during the last 3 months

          -  Certain cardiac disorders such as recent myocardial infarction (MI), severe congestive
             heart failure, certain types of abnormal cardiac rhythm

          -  Uncontrolled high blood pressure despite medications

          -  Uncontrolled, clinically significant active infection.

          -  Known HIV

          -  Known hypersensitivity to any of the components of CA4P, paclitaxel, carboplatin,
             bevacizumab, or radiologic contrast dyes.

        Details of the above and additional inclusion and exclusion criteria can be discussed with
        an investigator.