S0536: Cetuximab, Paclitaxel, Carboplatin, and Bevacizumab in Treating Patients With Advanced Non-Small Cell Lung Cancer
Condition: Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Bronchoalveolar Cell Lung Cancer; Large Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma of Lung; Adenocarcinoma, Bronchiolo-Alveolar
Intervention: cetuximab; paclitaxel; bevacizumab
Intervention description: Given IV; Given IV; Given IV
Intervention MeSH terms: Paclitaxel; Bevacizumab; Cetuximab; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 110.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Monoclonal antibodies, such as cetuximab and 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. Cetuximab may also stop the growth
      of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab may stop
      the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy,
      such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells,
      either by killing the cells or by stopping them from dividing. Giving cetuximab together with
      paclitaxel, carboplatin, and bevacizumab may kill more tumor cells. This phase II trial is
      studying how well giving cetuximab together with paclitaxel, carboplatin, and bevacizumab
      works in treating patients with advanced non-small cell lung cancer
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically proven newly diagnosed selected
             stage IIIB (T4 lesion due to malignant pleural effusion) or stage IV, advanced primary
             non-small cell lung cancer (adenocarcinoma, large cell carcinoma, or unspecified) or
             recurrent disease after previous surgery and/or irradiation; patients with tumors
             having squamous cell components > 50% are not eligible

          -  Patients with known brain metastases are not eligible; all patients must have a
             pretreatment CT or MRI scan of the brain to evaluate for CNS disease within 42 days
             prior to registration

          -  Patients may have measurable or non-measurable disease documented by CT, MRI, X-ray or
             physical exam; measurable disease must be assessed within 28 days prior to
             registration; pleural effusions, ascites and laboratory parameters are not acceptable
             as the only evidence of disease; non-measurable disease must be assessed within 42
             days prior to registration; all disease must be assessed and documented on the
             Baseline Tumor Assessment Form (Form #848)

          -  Patients must not have received any prior systemic chemotherapy or biologic therapy
             for non-small cell lung cancer; patients must not have received any adjuvant therapy
             for non-small cell lung cancer

          -  Prior radiation is permitted; however, at least three weeks must have elapsed since
             the completion of prior radiation therapy and patients must have recovered from all
             associated toxicities at time of registration; measurable or non-measurable disease
             must be outside the previous radiation field or a new lesion must be present

          -  At least four weeks must have elapsed since surgery (thoracic or other major
             surgeries) and patients must have recovered from all associated toxicities at the time
             of registration; measurable disease must be present outside the area of surgical
             resection; there must be no anticipation of need for major surgical procedures during
             protocol treatment

          -  Patients must not have received prior cetuximab, ZD1839, erlotinib or other
             investigational agents that target the EGFR pathway; patients must not have received
             prior VEGF-related agents; patients must not have received prior chimerized or murine
             monoclonal antibody therapy or have documented presence of human anti-mouse antibodies
             (HAMA)

          -  ANC >= 1,500/mcl

          -  Platelet count >= 100,000/mcl

          -  Hemoglobin >= 9 mg/dl

          -  Patients must have a serum creatinine =< institutional upper limit of normal (IULN)
             AND calculated or measured creatinine clearance >= 50 cc/min using the Cockroft-Gault
             Formula

          -  Urine protein must be screened by urine analysis for Urine Protein Creatinine (UPC)
             ratio; for UPC ratio > 0.5, 24-hour urine protein must be obtained and the level must
             be < 1,000 mg for patient enrollment

          -  Serum bilirubin =< 2 x IULN

          -  Either SGOT or SGPT =< 2 x IULN (if both SGOT and SGPT are done, both must be =< 2 x
             IULN)

          -  International Normalized Ratio (INR) =< 1.5; patients must not be taking full-dose
             anticoagulation therapy; patients may be enrolled initially if they are on low-dose
             warfarin (i.e., 1 mg daily)

          -  All patients must have a Zubrod performance status of 0 - 1

          -  Correlative science studies: institutions must have received IRB approval of S9925
             (the Lung Cancer Specimen Repository); patients must be offered participation in
             S9925; with the patient's consent, blood, plasma and tissue will be submitted for
             testing via S9925; patients must be registered separately to S9925 in order for
             institutions to receive credit for specimen submissions

          -  Patients must not have had hemoptysis >= 1/2 teaspoon within 3 months prior to
             registration

          -  Patients must not have >= grade 2 symptomatic neuropathy-sensory (National Cancer
             Institute [NCI] Common Terminology Criteria Version 3.0)

          -  Patients must not have documented evidence of acute hepatitis or have an active or
             uncontrolled infection

          -  Patients must not have the following: history (within past 6 months) of CVA,
             myocardial infarction or unstable angina; uncontrolled hypertension; New York Heart
             Association grade 2 or greater congestive heart failure; serious cardiac arrhythmia
             requiring medication; or clinically significant peripheral vascular disease

          -  Patients must not have had an open biopsy or significant traumatic injury within 28
             days prior to registration; patients must not have had a core biopsy within 7 days
             prior to registration

          -  Patients must not have serious or non-healing wound, ulcer or bone fracture

          -  Patients must not have history of abdominal fistula, gastrointestinal perforation or
             intraabdominal abscess within 28 days prior to registration

          -  Patients must have no known hypersensitivity of Chinese hamster ovary cell products or
             other recombinant human antibodies

          -  Patients must not have evidence of bleeding diathesis or coagulopathy

          -  Patients must be willing to provide prior smoking history as required on the S0536
             Prestudy Form (Form #54655)

          -  No other prior malignancy is allowed except for the following: adequately treated
             basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
             stage I or II cancer from which the patient is currently in complete remission, or any
             other cancer from which the patient has been disease-free for 5 years

          -  Pregnant or nursing women are not eligible for this trial; women/men of reproductive
             potential must not participate unless they have agreed to use an effective
             contraceptive method during protocol treatment and for at least 6 months following
             completion of bevacizumab treatment

          -  Patients must be informed of the investigational nature of this study and must sign
             and give written informed consent in accordance with institutional and federal
             guidelines

          -  At the time of patient registration, the treating institution's name and ID number
             must be provided to the Data Operations Center in Seattle in order to ensure that the
             current (within 365 days) date of institutional review board approval for this study
             has been entered into the data base