BLP25 Liposome Vaccine and Bevacizumab After Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Stage IIIA or Stage IIIB Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery
Condition: Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: bevacizumab; Tecemotide; carboplatin; cyclophosphamide; paclitaxel; radiotherapy
Intervention description: IV; IV; IV; IV; radiotherapy is given 5 days a week for 6½ weeks during concomitant chemoradiotherapy
Intervention MeSH terms: Paclitaxel; Cyclophosphamide; Bevacizumab; Carboplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 70.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer; adenocarcinoma of the lung

Summary:

      RATIONALE: Vaccines may help the body build an effective immune response to kill tumor cells.
      Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some
      block the ability of tumor cells to grow and spread. Others find tumor cells and help kill
      them or carry tumor-killing substances to them. Drugs used in chemotherapy work in different
      ways to stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving vaccine
      therapy together with bevacizumab after chemotherapy and radiation therapy may kill more
      tumor cells.

      PURPOSE: This phase II trial is studying the side effects of giving BLP25 liposome vaccine
      together with bevacizumab after chemotherapy and radiation therapy in treating patients with
      newly diagnosed stage IIIA or stage IIIB non-small cell lung cancer that cannot be removed by
      surgery.
    

Eligibility criteria:

        Step 1 Inclusion Criteria:

          -  Histologically confirmed newly diagnosed nonsquamous non-small cell lung cancer
             (NSCLC), including the following subtypes:

               -  Adenocarcinoma

               -  Large cell undifferentiated

               -  Bronchoalveolar cell

               -  non-small cell carcinoma, not otherwise specified

          -  Unresectable stage IIIA or stage IIIB disease

               -  Patients with stage IIIA disease with mediastinal lymph node enlargement between
                  1 cm and 2.0 cm on computerized tomography (CT) scan must have these nodes
                  biopsied (pathologic confirmation) to rule out resectability

               -  Metastases to contralateral mediastinal or supraclavicular nodes allowed

          -  Measurable or non-measurable disease, as defined by Response Evaluation Criteria in
             Solid Tumours (RECIST) criteria

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  White blood cell (WBC) ≥ 4,000/mm³ OR Absolute neutrophil count (ANC) ≥ 2,000/mm³

          -  Platelet count ≥ 140,000/mm³

          -  Hemoglobin ≥ 9.0 g/dL

          -  Total bilirubin ≤ 1.5 mg/dL

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT)+ ≤ 2.5 times upper
             limit of normal

          -  Serum creatinine ≤ 1.5 mg/mL OR creatinine clearance ≥ 45 mL/min

          -  Urine protein:creatinine ratio < 1.0 by urine dipstick OR < 1 g of protein by 24-hour
             urine collection

          -  INR ≤ 1.5 OR ≤ 3.0 if patient is on therapeutic anticoagulation

          -  PTT normal

          -  Fertile patients must use effective contraception before, during, and for ≥ 6 months
             after completion of bevacizumab

        Step 1 Exclusion Criteria:

          -  Significant pleural effusion

          -  CNS metastases by head CT scan or MRI within the past 4 weeks

          -  Pregnant or breast-feeding

          -  Prior chemotherapy or monoclonal antibodies for other cancers within 5 years prior to
             registration

          -  Prior chemotherapy for lung cancer

          -  Prior chest radiotherapy

          -  Ongoing (lasting > 14 days) or active infection or ongoing (lasting > 14 days) fever
             within the past 6 months

          -  Gross hemoptysis ≥ grade 2 (defined as ≥ ½ teaspoon of bright red blood per episode)
             within the past 3 months

          -  Bleeding ≥ grade 2 or any bleeding requiring intervention

          -  Clinically significant cardiovascular disease

          -  Myocardial infarction within the past 6 months

          -  New York Heart Association class III-IV congestive heart failure

          -  Unstable angina pectoris

          -  Serious cardiac arrhythmia requiring medication within the past 4 weeks

          -  History of hypertensive crisis or hypertensive encephalopathy

          -  Stroke or transient ischemic attack within the past 6 months

          -  Peripheral vascular disease ≥ grade 2 within the past 6 months

          -  Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the
             past 6 months

          -  Psychiatric illness or social situation that would limit compliance with study
             requirements

          -  History of uncontrolled hypertension (i.e., blood pressure ≥ 150/100 mm Hg) while on
             stable regimen of antihypertensive therapy

          -  Significant traumatic injury or serious non-healing wound, ulcer, or bone fracture
             within the past 4 weeks

          -  Concurrent major surgical procedure

          -  Having anticipated major surgical procedure(s) during the course of the study

          -  Concurrent daily aspirin (> 325 mg/day) or nonsteroidal anti-inflammatory agents
             (NSAIDs) known to inhibit platelet function

          -  Recognized immunodeficiency disease, including cellular immunodeficiencies,
             hypogammaglobulinemia or dysgammaglobulinemia, or hereditary or congenital
             immunodeficiencies

          -  Pre-existing medical condition requiring chronic steroids or immunosuppressive therapy

          -  Autoimmune disease

          -  Known hepatitis B or C

          -  Immunotherapy (e.g., interferon, interleukin, sargramostim [GM-CSF], or filgrastim
             [G-CSF]) within 28 days prior to registration

          -  Prior splenectomy

          -  Hypersensitivity to any component of bevacizumab

          -  Prior core biopsy or any other minor surgical procedure, excluding the placement of a
             vascular access device, within 7 days prior to registration

        Step 2 Inclusion Criteria:

          -  Serum creatinine ≤ 1.5 mg/ml or calculated creatinine clearance ≥ 45 ml/min

          -  Urine dipstick must be ≤ 0-1+. If urine dipstick results > 1+, 24 hour urine for
             protein must be obtained. Patients must have < 1g protein/24 hours to participate in
             the study

          -  Patient must be registered to step 2 within 28 days of completion of consolidation
             chemotherapy

          -  Patient must have met all eligibility requirements for Step 1

          -  Platelets ≥ 100,000/mm3

        Step 2 Exclusion Criteria:

          -  Progressive disease or unevaluable disease per RECIST criteria upon post-
             consolidation chemotherapy evaluation

          -  Autoimmune disease