Sorafenib and High-Dose Carboplatin, Paclitaxel, and External-Beam Radiation Therapy in Treating Patients With Stage III Non-Small Cell Lung Cancer
Lung Cancer
About this trial
This is an interventional treatment trial for Lung Cancer focused on measuring stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer, recurrent non-small cell lung cancer, adenocarcinoma of the lung, squamous cell lung cancer, large cell lung cancer, bronchoalveolar cell lung cancer, adenosquamous cell lung cancer
Eligibility Criteria
DISEASE CHARACTERISTICS:
Inclusion criteria:
Histologically or cytologically documented non-small cell lung cancer (NSCLC)
Any of the following subtypes allowed:
- Adenocarcinoma (including bronchoalveolar cell)
- Squamous cell carcinoma
- Large cell anaplastic carcinoma (including giant and clear cell carcinomas)
- Poorly differentiated (not otherwise specified) NSCLC
- No metastasis (patients must be M0)
- Stage IIIA (T1 or T2 with N2 or T3N1-2) or stage IIIB (T4 with any N or any T with N2 or N3) disease
- Measurable disease
Tumors adjacent to a vertebral body are allowed as long as all gross disease can be encompassed in the radiation boost field
- The boost volume must be limited to < 50% of the ipsilateral lung volume
Pleural effusion that is a transudate, cytologically negative, and nonbloody allowed if the radiation oncologists feel the tumor can still be encompassed within a reasonable field of radiotherapy
- Pleural effusions seen on the chest CT but too small to tap allowed
Exclusion criteria:
- Totally resected tumors
- Exudative, bloody, or cytologically malignant effusions
Known brain metastasis
- Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis
PATIENT CHARACTERISTICS:
Inclusion criteria:
- Zubrod performance status 0-1
- ANC ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin ≥ 9 g/dL (prior to transfusions)
- Total bilirubin ≤ 1.5 mg/dL
- AST or ALT ≤ 3 times upper limit of normal (ULN)
- Alkaline phosphatase ≤ 2.5 times ULN
- Glucose ≤ 2 times ULN
- Creatinine ≤ 2.0 mg/dL
- FEV_1 ≥ 1,200 mL
- Weight loss ≤ 10% over the past 3 months
- Not pregnant or nursing
- Negative pregnancy test
- Women of childbearing potential and male participants who are unwilling or unable to use an acceptable method of contraception throughout the study and for 4 weeks after completion of treatment or those who are using a prohibited contraceptive method
- INR < 1.5 or a PT/PTT within normal limits
Exclusion criteria:
- Known allergy to murine proteins or Cremophor EL
- Active pulmonary infection not responsive to conventional antibiotics
- History of severe chronic obstructive pulmonary disease requiring ≥ 3 hospitalizations over the past year
Cardiac disease including any of the following:
- Congestive heart failure > class II NYHA
- Unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months)
- Myocardial infarction within the past 6 months
- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
- Patients with neuropathy > grade 1
- Evidence of malignancy in the past 2 years except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other in situ cancer
- Uncontrolled hypertension defined as systolic blood pressure > 150 mm Hg or diastolic pressure > 90 mm Hg, despite optimal medical management
- Known HIV infection or chronic hepatitis B
- Active clinically serious infection > CTCAE grade 2
- Thrombolic or embolic events, such as a cerebrovascular accident including transient ischemic attacks, within the past 6 months
- Pulmonary hemorrhage or bleeding event ≥ CTCAE grade 2 within the past 4 weeks
- Any other hemorrhage or bleeding event ≥ CTCAE Grade 3 within the past 4 weeks
- Serious nonhealing wound, ulcer, or bone fracture
- Evidence or history of bleeding diathesis or coagulopathy
- Known or suspected allergy to sorafenib tosylate or any agent given in the course of this trial
- Any condition that impairs patient's ability to swallow whole pills
- Any malabsorption problem
- Significant traumatic injury within the past 4 weeks
PRIOR CONCURRENT THERAPY:
Inclusion criteria:
- Recovered from exploratory thoracotomy
- Concurrent anti-coagulation treatment with an agent such as warfarin or heparin allowed provided INR or PT/PTT requirements are met
Exclusion criteria:
- Prior systemic chemotherapy for lung cancer and/or thoracic/neck radiotherapy for any reason
- Prior surgical resection of present cancer
- Prior therapy with any molecular-targeted drugs (for lung cancer)
- Currently participating in other phase III therapeutic clinical trials and/or who have participated in other phase III therapeutic clinical trials in the previous 30 days
- Major surgery or open biopsy within the past 4 weeks
- Concurrent Hypericum perforatum (St. John's wort) or rifampin (rifampicin)
Other concurrent anticancer drugs, including hormonal, immunotherapeutic, or chemotherapeutic agents
- Steroids for acute symptom management, adrenal failure, septic shock, or as antiemetics allowed
- Hormones administered for nondisease-related conditions (e.g., insulin for diabetes) allowed
- Amifostine concurrently with radiotherapy or within 3 months of completion of radiotherapy
- Concurrent colony-stimulating factors (i.e., filgrastim [G-CSF] or sargramostim [GM-CSF])
Sites / Locations
- Arlington Cancer Center - Arlington
- Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
Arm I
Arm II
Patients receive chemoradiotherapy comprising paclitaxel, carboplatin, and high-dose external beam radiotherapy (HDRT) as in phase I. Patients also receive consolidation therapy comprising paclitaxel and carboplatin as in phase I.
Patients receive chemoradiotherapy comprising paclitaxel, carboplatin, and HDRT as in phase I. Patients also receive consolidation therapy comprising paclitaxel, carboplatin, and sorafenib tosylate at the MTD as in phase I, as well as maintenance therapy comprising sorafenib tosylate at the MTD as in phase I.