S0819: Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer
Condition: Recurrent Large Cell Lung Carcinoma; Recurrent Lung Adenocarcinoma; Recurrent Squamous Cell Lung Carcinoma; Stage IV Large Cell Lung Carcinoma; Stage IV Lung Adenocarcinoma; Stage IV Squamous Cell Lung Carcinoma
MeSH terms: Carcinoma; Adenocarcinoma; Lung Neoplasms; Adenocarcinoma of Lung; Recurrence
Intervention: Bevacizumab; Carboplatin; Cetuximab; Laboratory Biomarker Analysis; Paclitaxel
Intervention description: Given IV; Given IV; Given IV; Correlative studies; Given IV
Intervention MeSH terms: Paclitaxel; Bevacizumab; Carboplatin; Cetuximab; Albumin-Bound Paclitaxel; Antineoplastic Agents, Immunological; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1333.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial studies carboplatin and paclitaxel to compare how well they
      work with or without bevacizumab and/or cetuximab in treating patients with stage IV or
      non-small cell lung cancer that has returned after a period of improvement (recurrent). Drugs
      used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the
      growth of tumor cells, either by killing the cells, by stopping them from dividing, or by
      stopping them from spreading. Bevacizumab may prevent the growth of new blood vessels that
      tumor needs to grow. Cetuximab may also stop cancer cells from growing by binding and
      interfering with a protein on the surface of the tumor cell that is needed for tumor growth.
      It is not yet known whether giving carboplatin and paclitaxel are more effective with or
      without bevacizumab and/or cetuximab in treating patients with non-small cell lung cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically proven primary non-small cell lung
             cancer (adenocarcinoma, large cell carcinoma, squamous or unspecified); disease must
             be stage IV; disease may be either newly diagnosed or recurrent after previous surgery
             and/or irradiation; patients with additional lesions in an ipsilateral non-primary
             lobe without M1a or M1b disease will not be considered to have stage IV disease and
             are not eligible

          -  Patients must have a computed tomography (CT) or magnetic resonance imaging (MRI) scan
             of the brain to evaluate for central nervous system (CNS) disease within 42 days prior
             to registration; patient must not have brain metastases unless: (1) metastases have
             been treated and have remained controlled for at least two weeks following treatment,
             AND (2) patient has no residual neurological dysfunction off corticosteroids for at
             least 1 day

          -  Patients may have measurable or non-measurable disease documented by CT or MRI; the CT
             from a combined positron emission tomography (PET)/CT may be used to document only
             non-measurable disease unless it is of diagnostic quality; 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

          -  Patients must have tumor tissue available for submission that is sufficient for EGFR
             FISH testing and must agree to submission of these specimens; patients must also agree
             to submission of specimens for other translational medicine studies; patient must be
             offered participation in banking for future research

          -  Patients must not have received prior chemotherapy for any stage non-small cell lung
             cancer; patients must not have received prior platinum-based chemotherapy for any
             purpose; patient must not have received any cetuximab, gefitinib, erlotinib, or other
             investigational agents that target the EGFR pathway; patients must not have received
             for any purpose prior bevacizumab or other vascular endothelial growth factor
             (VEGF)-related agents; patients must not have received for any purpose prior
             chimerized or murine monoclonal antibody therapy or have documented presence of human
             anti-mouse antibodies (HAMA)

          -  Prior radiation is permitted; however, patients must have recovered from all
             associated toxicities at time of registration; in order to qualify as measurable,
             measurable disease must be outside the previous radiation field or must have
             progressed

          -  Time from surgical or biopsy procedures is dependent on whether it is planned for the
             patient to receive bevacizumab

               -  For patients who are bevacizumab-appropriate AND bevacizumab is planned: at least
                  28 days must have elapsed since major surgery (i.e. thoracotomy or video-assisted
                  thoracoscopic surgery [VATS] resection of lung cancer, open pleural biopsy or
                  another major surgical procedure such as abdominal surgery) or significant
                  traumatic injury; patients must have recovered from all associated toxicities at
                  the time of registration; there must be no anticipation of need for major
                  surgical procedures during protocol treatment; patients must not have had a core
                  biopsy, mediastinoscopy, pleurodesis, VATS pleural biopsy or VATS pericardial
                  window within 14 days prior to registration; patients must not have had a
                  percutaneous fine needle aspiration (FNA), thoracentesis or central venous access
                  device implanted within 7 days prior to registration; for other surgical
                  procedures not listed here, please contact the study coordinators

               -  For patients who are bevacizumab-inappropriate or bevacizumab is not planned: at
                  least 28 days must have elapsed since major surgery (i.e. thoracotomy or VATS
                  resection of lung cancer, open pleural biopsy or another major surgical procedure
                  such as abdominal surgery) or significant traumatic injury; patients must have
                  recovered from all associated toxicities at the time of registration; there must
                  be no anticipation of need for major surgical procedures during protocol
                  treatment; patients must not have had a core biopsy, mediastinoscopy,
                  pleurodesis, VATS pleural biopsy or VATS pericardial window within 7 days prior
                  to registration; patients must not have had a percutaneous fine needle aspiration
                  (FNA), or thoracentesis within 1 day prior to registration; patients may have had
                  a central venous access device placed at any time prior to registration; for
                  other surgical procedures not listed here, please contact the study coordinators

          -  Absolute neutrophil count (ANC) >= 1,500/mcl

          -  Platelet count >= 100,000/mcl

          -  Hemoglobin >= 9 g/dL

          -  Serum creatinine =< institutional upper limit of normal (IULN) AND calculated or
             measured creatinine clearance >= 50 cc/min using the following Cockroft-Gault formula

          -  For patients who will be receiving bevacizumab, 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; the urine protein used to calculate the UPC ratio must be obtained within
             14 days prior to registration; UPC or 24-hour protein is not required for patients who
             will not receive bevacizumab Note: UPC ratio of spot urine is an estimation of the
             24-hour urine protein excretion - a UPC ratio of 1 is roughly equivalent to a 24-hour
             urine protein of 1 gm

          -  Serum bilirubin =< 2 times IULN (for patients with liver metastases, bilirubin must be
             =< 5 X IULN)

          -  Serum glutamic oxaloacetic transaminase (SGOT) OR serum glutamate pyruvate
             transaminase (SGPT) =< 2 times IULN (for patients with liver metastases, either SGOT
             or SGPT must be =< 5 X IULN)

          -  Zubrod performance status 0-1

          -  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
             cerebrovascular accident (CVA), myocardial infarction or unstable angina; or at the
             time of registration, 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 have no known hypersensitivity to Chinese hamster ovary cell products or
             other recombinant human antibodies (examples include trastuzumab [Herceptin] and
             epoetin alpha)

          -  Patients must be willing to provide prior smoking history

          -  No other prior malignancy is allowed except for any of 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

               -  Any other cancer from which the patient has been disease-free for 5 years

          -  Patients must not be pregnant or nursing; women/men of reproductive potential must
             have agreed to use an effective contraceptive method; a woman is considered to be of
             "reproductive potential" if she has had menses at any time in the preceding 12
             consecutive months; in addition to routine contraceptive methods, "effective
             contraception" also includes heterosexual celibacy and surgery intended to prevent
             pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy,
             bilateral oophorectomy or bilateral tubal ligation; however, if at any point a
             previously celibate patient chooses to become heterosexually active during the time
             period for use of contraceptive measures outlined in the protocol, he/she is
             responsible for beginning contraceptive measures

          -  Patients or their legally authorized representative 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

          -  As a part of the Oncology Patient Enrollment Network (OPEN) registration process the
             treating institution's identity is provided in order to ensure that the current
             (within 365 days) date of institutional review board approval for this study has been
             entered in the system