RATIONALE: Drugs used in chemotherapy (CT), 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. Radiation therapy (RT) uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as panitumumab, 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. Giving these treatments before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known whether chemotherapy and radiation therapy are more effective when given with or without panitumumab in treating patients with non-small cell lung cancer. PURPOSE: This randomized phase II trial is studying chemotherapy and radiation therapy to see how well they work when given with or without panitumumab in treating patients with stage IIIA non-small cell lung cancer.
OBJECTIVES: Primary * Determine the mediastinal nodal clearance after completion of induction chemoradiotherapy with or without panitumumab in patients with stage IIIA non-small cell lung cancer. Secondary * Assess overall survival of these patients. * Evaluate patterns of first failure in these patients. * Determine the acute and late adverse events associated with these regimens. * Assess surgical morbidities in patients with resectable disease at reassessment. * Determine the correlation between pre- and post-treatment biomarkers (including epidermal growth factor receptor (EGFR) and ras mutation status) and outcomes (mediastinal nodal clearance and overall survival). * Evaluate the prognostic value of plasma osteopontin and microRNA for overall survival. * Assess the ability of FDG-PET/CT scan re-staging to predict outcome. OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive induction therapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, and 36. Patients also undergo intensity-modulated radiotherapy (IMRT) or 3-dimensional conformal radiotherapy (3D-CRT) once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Beginning approximately 6-12 weeks later, patients receive consolidation therapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1 and 21. * Arm II: Patients receive induction therapy comprising panitumumab IV over 1 hour on days 1, 8, 15, 22, 29, and 36 and paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 8, 15, 22, 29, and 36. Patients also undergo IMRT or 3D-CRT once daily on days 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47. Beginning approximately 6-12 weeks later, patients receive consolidation therapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1 and 21. * In both arms, patients with resectable disease and no disease progression may proceed to surgery (thoracotomy, lobectomy, or pneumonectomy) approximately 4-6 weeks after completion of induction therapy. After surgery, patients proceed to consolidation therapy. After completion of study treatment, patients are followed up at 6 weeks, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
71
Induction: 2.5 mg/kg, IV, days 1, 8, 15, 22, 29, 36 of radiation therapy before administration of chemotherapy and radiation therapy.
Induction: AUC=2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy. Consolidation, 6-12 weeks following surgery, AUC=6, IV, days 1 and 22.
Induction: 50 mg/m2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy. Consolidation, 6-12 weeks following surgery, 200 mg/m2, IV, days 1 and 22.
A lobectomy or pneumonectomy performed 4-6 weeks after completion of induction chemoradiation
Mercy Cancer Center at Mercy San Juan Medical Center
Carmichael, California, United States
Radiological Associates of Sacramento Medical Group, Incorporated
Sacramento, California, United States
Penrose Cancer Center at Penrose Hospital
Colorado Springs, Colorado, United States
Lucille P. Markey Cancer Center at University of Kentucky
Lexington, Kentucky, United States
CCOP - Ochsner
New Orleans, Louisiana, United States
Mediastinal Nodal Clearance After Completion of Induction Chemoradiotherapy With or Without Panitumumab.
The assessment of whether mediastinal nodes which were involved at the time of study registration were clear of disease following induction chemoradiotherapy with or without panitumumab; the assessment is made at the time of surgery 4-6 weeks after chemoradiation. If surgery could not be performed, the patient was considered as not having had mediastinal nodal clearance.
Time frame: From date of randomization to time of protocol surgery, approximately 12 weeks.
Overall Survival
Survival time was calculated from the date of randomization to the date of death from any cause or the date of last follow-up. The Kaplan-Meier method was used to estimate the overall survival rates. One-year survival rates were estimated, not compared.
Time frame: Patients are followed until death. Analysis occurs at time of primary analysis, approximately five years from start of study
Patterns of First Failure
The first failure site will be tabulated, not compared.
Time frame: Patients are followed until death. Analysis occurs at time of primary analysis, approximately five years from start of study.
Percentage of Patients With Grade 3 or Higher Acute and Late Adverse Events
Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. Does not include surgical morbidities. An acute adverse event is defined as any grade 3 or worse toxicity occurring during protocol treatment and within 30 days from the end of protocol treatment that is possibly, probably, or definitely related to treatment. Acute adverse events are any adverse events occurring within 30 days of the end of all protocol treatment. Late adverse events are any adverse events occurring after 30 days after the end of all protocol treatment.
Time frame: Patients are followed until death. Analysis occurs at time of primary analysis, approximately five years from start of study.
Surgical Morbidities in Patients With Resectable Disease at Reassessment
A surgical morbidity is any toxicity occurring within 30 days of protocol surgery, as evaluated using CTCAE v4.0. Rates of grade 3 and higher surgical morbidity were calculated; the rates across arms were not compared.
Time frame: From date of surgery to 30 days following surgery.
Ability of FDG-PET/CT Scan Data to Predict Outcome
Time frame: Patients are followed until death. Analysis occurs at time of primary analysis, approximately five years from start of study.
Response Rate
Patients are assessed for best response to protocol treatment using the RECIST criteria. The response rate was calculated as the number of patients who have a complete response (CR) or partial response (PR) divided by the total number of analyzable patients at completion of induction chemoradiation +/- panitumumab and prior to anticipated surgery in each arm. Patients without a documented assessment are considered as not having a CR or PR. Rates are not compared across arms.
Time frame: From date of randomization to time of protocol surgery, approximately 12 weeks.
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Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, United States
St. Agnes Hospital Cancer Center
Baltimore, Maryland, United States
Cancer Institute at St. Joseph Medical Center
Towson, Maryland, United States
Boston University Cancer Research Center
Boston, Massachusetts, United States
Fairview Southdale Hospital
Edina, Minnesota, United States
...and 21 more locations