A Randomized, Phase III Study Comparing Carboplatin/Paclitaxel or Carboplatin/Paclitaxel/Bevacizumab with or without Concurrent Cetuximab in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC)
Trial Purpose and Description
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 or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab and cetuximab, 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. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. 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. This randomized phase III trial is studying carboplatin and paclitaxel to compare how well they work with or without bevacizumab and/or cetuximab in treating patients with stage IV or recurrent non-small cell lung cancer.
- 18 Years and older
- 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, as defined in Section 4.0. 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 CT or MRI scan of the brain to evaluate for 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.
- Patients may have measurable or non-measurable disease (see Section 10.1) documented by CT or MRI. The CT from a combined PET/CT may be used to document only non-measurable disease unless it is of diagnostic quality as defined in Section
- 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 #29689). See Sections 15.2 and 19.6 for guidelines and submission instructions for required central radiology review.
- Translational Medicine Studies: Patients must have tumor tissue available for submission that is sufficient for EGFR FISH testing and must agree to submission of these specimens as defined in Section 15.0. Patients must also agree to submission of specimens for other translational medicine studies as outlined in Section 15.0. Patient must be offered participation in banking for future research.
- Patients must not have received for any purpose prior chemotherapy. Patients 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 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 per Section 10.1a, 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.
a. For patients who are bevacizumab-appropriate AND bevacizumab is planned: At least 28 days must have elapsed since major surgery (i.e. thoracotomy or VATS resection of lung cancer 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 or VATS pericardial window within 14 days prior to registration.
b. 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 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 or VATS pericardial window within 7 days prior to registration
- Patients must have an ANC ≥ 1,500/mcl, platelet count ≥ 100,000/mcl, and hemoglobin ≥ 9 g/dL obtained within 14 days prior to registration.
- Patients must have a serum creatinine ≤ institutional upper limit of normal (IULN) AND calculated or measured creatinine clearance ≥ 50 cc/min using the following Cockroft- Gault Formula. These tests must have been performed within 14 days prior to registration.
- 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. UPC ratio is calculated using one of the following formulas: [urine protein]/[urine creatinine] – if both protein and creatinine are reported in mg/dL [(urine protein) x 0.088]/[urine creatinine] – if urine creatinine is reported in mmol/L
- Patients must have adequate hepatic function documented by serum bilirubin ≤ 2 X IULN and either SGOT or SGPT ≤ 2 x IULN within 14 days prior to registration (if both SGOT and SGPT are done, both must be ≤ 2 x IULN). For patients with liver metastases, bilirubin and either SGOT or SGPT must be ≤ 5 x IULN.
- All patients must have a Zubrod Performance Status of 0 - 1 (see Section 10.4).
- Patients must not have ≥ Grade 2 symptomatic neuropathy-sensory (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 (see Appendix 19.3); 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 as required on the S0819 Prestudy Form (Form #36042).
- 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 because of the increased risk of fetal harm including fetal death from the chemotherapeutic agents. 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.
- Southwest Oncology Group
- December 2011
- Last Updated:
- Study HIC#:
Clinicaltrials.gov ID: Yale1479870