Sorafenib in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
This phase II trial is studying how well sorafenib works in treating patients with stage IIIB or stage IV non-small cell lung cancer. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It may also stop the growth of non-small cell lung cancer by blocking blood flow to the tumor.

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. Determine the response rate in patients with stage IIIB or IV non-small cell lung cancer treated with sorafenib. II. Determine the clinical toxic effects of this drug in these patients. SECONDARY OBJECTIVES: I. Determine the 24-week progression-free survival rate in patients treated with this drug. II. Determine the overall survival of patients treated with this drug. III. Determine the time to disease progression in patients treated with this drug. IV. Correlate predictive disease markers (K-ras and B-raf mutations and ERK/pERK, AKT/pAKT, and VEGFR2/p-VEGFR2 expression) in these patients with the activity of this drug. OUTLINE: This is a multicenter study. Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 6 months for up to 5 years.

Official Title
-----------------
Phase II Study of the Raf Kinase Inhibitor BAY43-9006 in Patients With Advanced Non-Small Cell Lung Cancer

Conditions
-----------------
Recurrent Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

Intervention / Treatment
-----------------
* Drug: sorafenib tosylate
* Other: laboratory biomarker analysis


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), meeting 1 of the following stage criteria: Stage IIIB with pleural effusion Stage IV Measurable disease At least 1 lesion ≥ 2.0 cm by conventional techniques OR ≥ 1.0 cm by spiral CT scan The following are not considered measurable disease: Bone lesions Leptomeningeal disease Ascites Pleural/pericardial effusion Inflammatory breast disease Lymphangitis cutis/pulmonis Abdominal masses not confirmed and followed by imaging techniques Cystic lesions No known brain metastases, even if treated and stable Performance status - ECOG 0-2 At least 12 weeks Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 10 g/dL No bleeding diathesis Bilirubin ≤ 2 times upper limit of normal (ULN) AST ≤ 3 times ULN (5 times ULN if hepatic metastasis present) Creatinine ≤ 1.5 times ULN No uncontrolled hypertension Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No known HIV positivity HIV negative Able to swallow tablets No uncontrolled infection No other severe underlying disease that would preclude study participation No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or adequately treated noninvasive carcinomas No prior immunotherapy, biologic therapy, or gene therapy No concurrent prophylactic colony-stimulating factors At least 4 weeks since prior low-dose weekly chemotherapy as a radiosensitizer No other prior chemotherapy for NSCLC No concurrent chemotherapy See Chemotherapy At least 4 weeks since prior radiotherapy No prior radiotherapy to ≥ 30% of bone marrow No concurrent radiotherapy Concurrent palliative radiotherapy to nontarget lesions (e.g., painful pre-existing bony metastasis) allowed Prior adjuvant therapy allowed provided recurrent disease occurred > 6 months after completion of adjuvant therapy No prior systemic therapy for NSCLC, including all novel targeted agents (e.g., gefitinib or erlotinib) No concurrent therapeutic anticoagulation Prophylactic anticoagulation (e.g., low-dose warfarin) for venous and arterial devices allowed provided PT, INR, and PTT requirements are met No other concurrent anticancer agents or therapies No other concurrent investigational agents or therapies

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 tosylate)<br>Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: sorafenib tosylate<br>* Given orally<br>* Other names: SFN;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed tumor response according to RECIST criteria | The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated using the Duffy-Santner approach. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | The proportion of patients who are progression-free at 24-weeks will be computed and binomial confidence intervals for the true success proportion will be calculated. | At 24 weeks | 
| Survival time | Estimated using the method of Kaplan-Meier. | From registration to death due to any cause, assessed up to 5 years | 
| Time-to-disease progression | Estimated using the method of Kaplan-Meier. | From registration to documentation of disease progression, assessed up to 5 years |