Pemetrexed Disodium, Carboplatin, and Radiation Therapy With or Without Cetuximab in Treating Patients With Stage III Non-Small Cell Lung Cancer
Condition: Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: cetuximab; carboplatin; pemetrexed disodium; radiation therapy
Intervention description: 400 mg/sq m IV over 120 min: Day 1; Week 1 250 mg/sq m IV over 60 min weekly for 6 more weeks.; AUC = 5 q 21 days for 4 cycles; 500 mg/sq m IV q 21 days during chemoradiation and consolidation chemotherapy phases; Thoracic radiotherapy: 70 Gy for 7 weeks beginning on Day 1.
Intervention MeSH terms: Carboplatin; Pemetrexed; Cetuximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 109.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer; squamous cell lung cancer; large cell lung cancer; adenocarcinoma of the lung; bronchoalveolar cell lung cancer

Summary:

      RATIONALE: Pemetrexed disodium may stop the growth of tumor cells by blocking some of the
      enzymes needed for cell growth. Drugs used in chemotherapy, such as 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 uses high-energy x-rays to kill tumor cells. Monoclonal
      antibodies, such as 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. Cetuximab may also make tumor cells more sensitive to
      radiation therapy. Giving pemetrexed disodium, carboplatin, and radiation therapy together
      with cetuximab may kill more tumor cells.

      PURPOSE: This randomized phase II trial is studying how well giving pemetrexed disodium and
      carboplatin together with radiation therapy with or without cetuximab works in treating
      patients with stage III non-small cell lung cancer that cannot be removed by surgery.
    

Eligibility criteria:

        1. Histologically or cytologically documented NSCLC, including squamous cell carcinoma,
             adenocarcinoma including bronchoalveolar cell, and large cell anaplastic carcinoma
             (including giant and clear cell carcinomas)

          2. Eligible Disease Stages: Inoperable IIIA and Selected IIIB - Patients entered must be
             considered unresectable or inoperable. Patients do not need to have a mediastinoscopy.

             A size of 2 cm or greater by CT is a sufficient criterion for the diagnosis of
             mediastinal lymph node (N2 or N3) involvement by malignancy. If the largest
             mediastinal lymph node is less than 2 cm in diameter, a biopsy confirmation of
             mediastinal nodal involvement is required.

               1. The following patients are eligible:

                    -  Patients must be M0

                    -  Patients with any T with N2 or N3 are eligible

                    -  Patients with T3, N1-N3 disease are eligible if deemed unresectable

                    -  Patients with T4, any N are eligible provided the T4 status is not
                       determined because of malignant effusion

                    -  Patients with contralateral mediastinal disease (N3) are eligible if all
                       gross disease can be encompassed in the radiation field in accordance with
                       the homogeneity criteria

                    -  Patients with a pleural effusion, which is a transudate, cytologically
                       negative and non-bloody, are eligible if the radiation oncologist feels the
                       tumor can be encompassed within a reasonable field of radiotherapy

                    -  If a pleural effusion can be seen on the chest CT but not on CXR and is too
                       small to tap, the patient will be eligible. Patients who develop a new
                       pleural effusion after thoracotomy or other invasive thoracic procedure will
                       be eligible.

               2. The following patients are NOT eligible:

                    -  Patients with T3, N0 disease

                    -  Patients with M1 disease

                    -  Patients with atelectasis of the entire lung

                    -  Patients with direct invasion of vertebral body

                    -  Patients with scalene, supraclavicular, or contralateral hilar node
                       involvement

                    -  Patients with exudative, bloody, or cytologically malignant effusions

          3. Patients must have Measurable Disease: Lesions that can be accurately measured in at
             least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional
             techniques or as ≥10 mm with spiral CT scan. Lesions that are not considered
             measurable include bone lesions, leptomeningeal disease, ascites, pleural/pericardial
             effusion, abdominal masses that are not confirmed and followed by imaging techniques,
             cystic lesions and tumor lesions situated in a previously irradiated area.

          4. Prior Therapy: ≥ 2 weeks since formal exploratory thoracotomy. No prior chemotherapy
             for NSCLC, chest radiation therapy or therapy that specifically and directly targets
             the EGFR pathway

          5. ECOG performance status 0-1

          6. Positron Emission Tomography (PET) using 18 fluorodeoxyglucose (FDG) must be negative
             for distant metastasis. PET imaging is mandatory.

          7. Weight loss of ≤ 10% in the past 3 months

          8. No "currently active" second malignancy other than non-melanoma skin cancers. Patients
             are not considered to have a "currently active" malignancy if they have completed
             therapy and are considered by their physician to be at less than 30% risk of relapse.

          9. Non-pregnant and non-nursing because of significant risk to the fetus/infant

         10. Age ≥ 18 years

         11. No patients with uncontrolled intercurrent illness including, but not limited to,
             ongoing or active infection, symptomatic congestive heart failure, unstable angina
             pectoris, cardiac arrhythmia, or psychiatric illness.

         12. No HIV-positive patients receiving combination anti-retroviral therapy because
             patients with immune deficiency are at increased risk of lethal infections when
             treated with marrow-suppressive therapy

         13. No known history of hypersensitivity to carboplatin, pemetrexed or a monoclonal
             antibody

         14. Required Initial Laboratory Values:

               1. Granulocytes ≥ 1,500/mcl

               2. Platelets ≥ 100,000/mcl

               3. Calculated Creatinine Clearance ≥ 45 ml/min

               4. Bilirubin < 1.5 x ULN

               5. AST/ALT < 3 x ULN

               6. Alkaline Phosphatase < 3 x ULN