Sorafenib in Treating Non-Smokers or Former Light Smokers With Relapsed or Refractory Stage IIIB or Stage IV Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. PURPOSE: This phase II trial is studying how well sorafenib works in treating non-smokers or former light smokers with relapsed or refractory stage IIIB or stage IV non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary To determine the efficacy of sorafenib tosylate, in terms of 6-month progression-free survival rate, in non-smokers or former light smokers with relapsed or refractory stage IIIB or IV non-small cell lung cancer. Secondary To determine the 1-year survival rate in patients treated with this drug. To assess the frequency and severity of adverse events associated with this drug in these patients. To investigate the mutational status of EGFR (epidermal growth factor receptor), ALK (anaplastic lymphoma kinase), ROS1, and K-Ras(Kirsten rat sarcoma viral oncogene homolog)in archived tumor samples from these patients. OUTLINE: Patients receive oral sorafenib tosylate twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Archived tumor tissue samples are analyzed for mutations of EGFR, ALK, ROS1, and K-Ras by PCR (polymerase chain reaction) and DNA (deoxyribonucleic acid) sequencing. After completion of study treatment, patients are followed every 3 months.

Official Title
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A Phase II Study of Single Agent Sorafenib in Non-small Cell Lung Cancer Patients Who Never Smoked or Were Former Light Smokers.

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: sorafenib


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed non-small cell lung cancer Stage IIIB or IV disease Recurrent disease after prior surgery, chemotherapy, or radiotherapy No squamous cell histology or mixed tumor with > 50% squamous cells Non-smoker (smoked ≤ 100 cigarettes in lifetime) OR former light smoker (smoked > 100 cigarettes but ≤ 10 pack years AND quit smoking ≥ 1 year ago) No known brain metastasis Patients with neurological symptoms must undergo a CT scan or MRI of the brain to exclude brain metastasis PATIENT CHARACTERISTICS: ECOG(Eastern Cooperative Oncology Group)performance status 0-2 ANC (Absolute Neutrophil Count)≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ ALT (Alanine Aminotransferase Test) and AST (Aspartate Aminotransferase Test) ≤ 2.5 times upper limit of normal (ULN) Alkaline phosphatase ≤ 2.5 times ULN Bilirubin ≤ 1.5 mg/dL Creatinine clearance ≥ 50 mL/min INR (International Normalized Ratio) < 1.5 OR PT/PTT (Prothrombin time/partial thromboplastin time)normal Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception prior to, during, and for ≥ 3 months after completion of study treatment No cardiac disease, including any of the following: New York Heart Association class III-IV congestive heart failure Unstable angina (anginal symptoms at rest) New-onset angina within the past 3 months Myocardial infarction within the past 6 months No cardiac ventricular arrhythmias requiring anti-arrhythmic therapy No uncontrolled hypertension (i.e., systolic blood pressure [BP] > 150 mm Hg or diastolic BP > 90 mm Hg) despite optimal medical management No thrombolic or embolic events (e.g., cerebrovascular accident, including transient ischemic attacks) within the past 6 months No pulmonary hemorrhage or bleeding event ≥ CTCAE (Common Terminology Criteria for Adverse Events)grade 2 within the past 4 weeks No other hemorrhage or bleeding event ≥ CTCAE grade 3 within the past 4 weeks No active clinically serious infection > CTCAE grade 2 No serious non-healing wound, ulcer, or bone fracture No evidence or history of bleeding diathesis or coagulopathy No known HIV infection or chronic hepatitis B or C No other malignancy except for any of the following: Adequately treated basal cell or squamous cell skin cancer In situ cervical cancer Other cancer from which the patient has been disease-free for ≥ 5 years with a low probability of recurrence No condition that impairs the patient's ability to swallow whole pills No malabsorption problems No known or suspected allergy to sorafenib tosylate or any agent given in the course of this study No significant traumatic injury within the past 4 weeks PRIOR CONCURRENT THERAPY: See Disease Characteristics No more than one prior systemic chemotherapy treatment for metastatic disease Prior treatment with EGFR inhibitors is not considered chemotherapy More than 4 weeks since prior major surgery or open biopsy No prior sorafenib tosylate No concurrent St. John's wort or rifampin Concurrent anticoagulation with warfarin or heparin allowed

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment: Sorafenib<br>Sorafenib will be administered at a dose of 400 mg taken twice daily, continuously on a 28 day cycle. | Drug: sorafenib<br>* administered orally at 400 mg taken twice daily , continuously on a 28 day cycle as an outpatient.<br>* Other names: sorafenib tosylate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival at 6 Months | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions, or similar definition as accurate and appropriate | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival Rate | Determine the one year survival rate in Non/Light smokers with advanced and previouslytreated NSCLC | Up to 2 years | 
| Incidence of Adverse Events Sssessed by Common Terminology Criteria for Adverse Events (CTCAE) | Assess the frequency and severity of adverse events associated with Sorafenib in this patient population Non/Light smokers with advanced and previously treated NSCLC. | Up to 2 years | 
| Mutational Status for EGFR or Kras |  | up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, adenocarcinoma of the lung, bronchoalveolar cell lung cancer, large cell lung cancer