Chemotherapy and Radiation Therapy With or Without Panitumumab in Treating Patients With Stage IIIA Non-Small Cell Lung Cancer
Condition: Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: panitumumab; carboplatin; paclitaxel; surgery
Intervention description: 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
Intervention MeSH terms: Paclitaxel; Carboplatin; Panitumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 71.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage IIIA non-small cell lung cancer; adenocarcinoma of the lung; adenosquamous cell lung cancer; bronchoalveolar cell lung cancer; large cell lung cancer; squamous cell lung cancer

Summary:

      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.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed* non-small cell lung cancer (NSCLC), including any of the
             following histologies:

               -  Adenocarcinoma

               -  Adenosquamous

               -  Large cell carcinoma

               -  Squamous cell carcinoma

               -  Non-lobar and non-diffuse bronchoalveolar cell carcinoma

               -  NSCLC not otherwise specified NOTE: *Documentation of NSCLC may originate from
                  the mediastinal node biopsy or aspiration

          -  Stage IIIA (T1-T3) disease with a single primary lung parenchymal lesion AND positive
             ipsilateral mediastinal node or nodes (N2) with or without positive ipsilateral hilar
             nodes (N1)

               -  N2 nodes must be separate from primary tumor by either CT scan or surgical
                  exploration

               -  Maximum nodal diameter of involved N2 nodes cannot exceed 3.0 cm

               -  N2 status must be pathologically confirmed to be positive by one of the following
                  methods*:

                    -  Mediastinoscopy

                    -  Mediastinotomy (Chamberlain procedure)

                    -  Transesophageal needle biopsy using endoscopic ultrasound (EUS-TBNA)

                    -  Endobronchial ultrasound biopsy using endoscopic ultrasound guidance
                       (EBUS-TBNA)

                    -  Thoracotomy

                    -  Video-assisted thoracoscopy

                    -  Transbronchial needle biopsy by Wang technique (TBNA)

                    -  Fine-needle aspiration under CT guidance NOTE: *PET positivity in the
                       ipsilateral mediastinal lymph nodes is not sufficient to establish N2 nodal
                       status

               -  Ipsilateral mediastinal nodes associated with right-sided tumor must be biopsied
                  unless all of the following are true:

                    -  Tumor is left sided

                    -  Paralyzed left true vocal cord documented by bronchoscopy or indirect
                       laryngoscopy

                    -  Nodes visible in the anterior/posterior (level 5) region on CT scan

                    -  Distinct primary tumor separate from nodes visible on CT scan

                    -  Histologic (biopsy) or cytologic (needle aspiration or sputum) proof of
                       non-small cell histology from the primary tumor

               -  If lymph nodes in the contralateral mediastinum and neck are visible on contrast
                  CT scan of the chest and are > 1.0 cm in short axis or if contralateral
                  involvement is suggested by PET scan, then the nodes must be confirmed to be
                  negative

          -  Measurable disease as determined by contrast-enhanced CT scan

               -  Primary lung tumor distinct from mediastinal lymph nodes

          -  If a pleural effusion is present, the following criteria must be met to exclude
             malignant involvement (incurable M1a disease):

               -  When pleural fluid is visible on both the CT scan and on a chest x-ray, a
                  pleuracentesis is required to confirm that the pleural fluid is cytologically
                  negative.

               -  Exudative pleural effusions are excluded, regardless of cytology;

               -  Effusions that are minimal (i.e. not visible under ultrasound guidance) that are
                  too small to safely tap are eligible.

          -  No palpable lymph nodes in the supraclavicular areas or higher in the neck, unless
             proven to be benign by fine-needle aspiration or biopsy

          -  No distant metastases

        PATIENT CHARACTERISTICS:

          -  Zubrod performance status 0-1

          -  Absolute neutrophil count (ANC) ≥ 1,500/mm³

          -  Platelet count ≥ 100,000/mm³

          -  Hemoglobin ≥ 10.0 g/dL (transfusion allowed)

          -  Creatinine clearance ≥ 60 mL/min

          -  Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times ULN

          -  Alkaline phosphatase ≤ 2.5 times ULN

          -  Serum albumin > 3.0 g/dL

          -  Serum magnesium normal (supplementation allowed)

          -  Not pregnant

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for 6 months after
             completion of treatment

          -  Forced expiratory volume at one second (FEV1) ≥ 2.0 L OR predicted post-resection FEV1
             ≥ 0.8 L

          -  Diffusion capacity ≥ 50% predicted

          -  No other invasive malignancy within the past 3 years, except nonmelanoma skin cancer
             or carcinoma in situ of the breast, oral cavity, or cervix

          -  No severe, active co-morbidity, including any of the following:

               -  Current uncontrolled cardiac disease (e.g., uncontrolled hypertension, unstable
                  angina, myocardial infarction within the past 6 months, uncontrolled congestive
                  heart failure, or cardiomyopathy with decreased ejection fraction (<50%)

               -  Acute bacterial or fungal infection requiring IV antibiotics

               -  Chronic obstructive pulmonary disease exacerbation or other respiratory illness
                  requiring hospitalization or that would preclude study therapy within the past 4
                  weeks

               -  Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

               -  AIDS or known HIV positivity

          -  No unintentional weight loss ≥ 5% of body weight within the past 6 months

          -  No prior severe infusion reaction to a monoclonal antibody

          -  No pre-existing peripheral neuropathy ≥ grade 2

        PRIOR CONCURRENT THERAPY:

          -  No prior systemic chemotherapy or biological therapy (including erlotinib
             hydrochloride or similar agents) for the study cancer

               -  Prior chemotherapy for a different cancer allowed

          -  No prior radiotherapy to the region of the study cancer that would result in overlap
             of radiotherapy fields

          -  No prior therapy that specifically and directly targets the EGFR pathway