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High-Dose or Standard-Dose Radiation Therapy and Chemotherapy With or Without Cetuximab in Treating Patients With Newly Diagnosed Stage III Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery
Trial ID: NCT00533949
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as paclitaxel, carboplatin 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 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. It is not yet known whether high-dose radiation therapy is more effective than standard-dose radiation therapy when given together with combination chemotherapy with or without cetuximab in treating patients with non-small cell lung cancer. PURPOSE: This randomized phase III trial is studying high-dose or standard-dose radiation therapy given together with chemotherapy with or without cetuximab to see how well they work in treating patients with newly diagnosed stage III non-small cell lung cancer that cannot be removed by surgery.
A Randomized Phase III Comparison of Standard-Dose (60 Gy) Versus High-Dose (74 Gy) Conformal Radiotherapy With Concurrent and Consolidation Carboplatin/Paclitaxel +/- Cetuximab (IND #103444) in Patients With Stage IIIA/IIIB Non-Small Cell Lung Cancer
1. Pathologically proven (either histologic or cytologic) diagnosis of Stage IIIA or IIIB
non-small cell lung cancer (NSCLC); excluding patients with N3 disease based on
supraclavicular or contralateral hilar adenopathy, [according to American Joint
Committee on Cancer (AJCC) Staging, 6th edition; see appendix III] within 12 weeks of
registration; patients who present with N2 or N3 disease and an undetectable NSCLC
primary tumor also are eligible.
2. Patients must be considered unresectable or inoperable; Note: Patients who have had a
nodal recurrence after surgery for an early-stage NSCLC are eligible if the following
criteria are met:
- Nodal recurrence must be N1 or N2; N3 is not eligible.
- The initial primary must have been staged as T1-2, N0, M0.
- The node must be biopsied within 12 weeks of registration.
- The node must be measurable.
- The patient must not have received prior chemotherapy or radiation for this lung
- Prior curative surgery must have been at least 6 months prior to the nodal
- The exception to a prior invasive malignancy does not apply to the initial lung
3. Stage III A or B disease, including no distant metastases, based upon the following
minimum diagnostic workup are acceptable:
- History/physical examination, including documentation of height, weight, body
surface area (BSA), and vital signs within 8 weeks prior to registration;
- Computed tomographic (CT)/Magnetic Resonance Imaging (MRI) imaging of the lung
and upper abdomen through the adrenal glands within 6 weeks prior to
- An MRI of the brain with contrast (or CT with contrast if MRI is medically
contraindicated) within 6 weeks prior to registration; Note: The use of
intravenous contrast is required for the MRI or CT. An MRI without contrast is
only permitted if the patient has a contrast allergy.
- Whole-body fluorodeoxyglucose (FDG) - Positron Emission Tomography(PET) or PET/CT
or if no PET is available, a bone scan is required within 6 weeks prior to
registration; Note: If a PET is done that shows clear adrenals and lungs, then a
CT scan of chest only is permitted.
4. If a pleural effusion is present, the following criteria must be met to exclude
malignant involvement (incurable T4 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
- Exudative pleural effusions are excluded, regardless of cytology;
- Effusions that are minimal (i.e. not visible on chest x-ray) that are too small
to safely tap are eligible.
5. Patients must have measurable or evaluable disease.
6. Patients with post-obstructive pneumonia are eligible.
7. Patients must be at least 3 weeks from prior thoracotomy (if performed).
8. Zubrod Performance Status 0-1;
9. Age ≥ 18;
10. Pulmonary function tests (PFTs) including forced expiratory volume in one second
(FEV1) within 12 weeks prior to registration; for FEV1, the best value obtained pre-
or post bronchodilator must be ≥ 1.2 liters/second or ≥ 50% predicted.
11. Complete blood count (CBC)/differential obtained within 2 weeks prior to registration
on study, with adequate bone marrow function defined as follows:
- Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3;
- Platelets ≥ 100,000 cells/mm3;
- Hemoglobin ≥ 10.0 g/dl (Note: The use of transfusion or other intervention to
achieve Hgb ≥ 10.0 g/dl is acceptable.)
12. Serum creatinine within normal institutional limits or creatinine clearance ≥60
13. Bilirubin must be within or below normal institutional limits;
14. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) < 2.5 x the
institutional upper limit of normal (IULN);
15. Patient must sign study specific informed consent prior to study entry.
1. N3 supraclavicular disease;
2. Greater than minimal, exudative, or cytologically positive pleural effusions;
3. Involved contralateral hilar nodes (i.e. greater than 1.5 cm on short axis or positive
on PET scan);
4. ≥ 10% weight loss within the past month;
5. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
for a minimum of 3 years; non-invasive conditions such as carcinoma in situ of the
breast, oral cavity, or cervix are all permissible.
6. Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a
different cancer is allowable.
7. Prior radiotherapy to the region of the study cancer that would result in overlap of
radiation therapy fields;
8. Prior therapy that specifically and directly targets the epidermal growth factor
receptor (EGFR) pathway;
9. Prior severe infusion reaction to a monoclonal antibody;
10. Severe, active co-morbidity, defined as follows:
- Significant history of uncontrolled cardiac disease; i.e., uncontrolled
hypertension, unstable angina, myocardial infarction within the last 6 months,
uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection
- Transmural myocardial infarction within the last 6 months;
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time
- Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy within 30 days before
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
- Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease
Control and Prevention (CDC) definition; note, however, that human
immunodeficiency virus (HIV) testing is not required for entry into this
protocol. The need to exclude patients with AIDS from this protocol is necessary
because the treatments involved in this protocol may be significantly
immunosuppressive. Protocol-specific requirements may also exclude
11. Pregnancy or women of childbearing potential and men who are sexually active and not
willing/able to use medically acceptable forms of contraception; this exclusion is
necessary because the treatment involved in this study may be significantly
12. Any history of allergic reaction to paclitaxel or other taxanes, or to carboplatin;
13. Uncontrolled neuropathy grade 2 or greater regardless of cause.
radiation: 60 Gy RT
radiation: 74 Gy RT
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