RATIONALE: 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.

PURPOSE: This phase II trial is studying how well sorafenib works in treating patients with stage IIIB or stage IV non-small cell lung cancer.

Condition	Treatment or Intervention	Phase
stage IIIB non-small cell lung cancer stage IV non-small cell lung cancer recurrent non-small cell lung cancer	Drug: sorafenib  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: enzyme inhibitor therapy  Procedure: growth factor antagonist therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the response rate in patients with stage IIIB or IV non-small cell lung cancer treated with sorafenib.
• Determine the clinical toxic effects of this drug in these patients.

Secondary

• Determine the 24-week progression-free survival rate in patients treated with this drug.
• Determine the overall survival of patients treated with this drug.
• Determine the time to disease progression in patients treated with this drug.
• 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.

PROJECTED ACCRUAL: A total of 20-46 patients will be accrued for this study within 2-10.6 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL
• No bleeding diathesis

Hepatic

• Bilirubin ≤ 2 times upper limit of normal (ULN)
• AST ≤ 3 times ULN (5 times ULN if hepatic metastasis present)

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• No uncontrolled hypertension

Other

• 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

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior immunotherapy, biologic therapy, or gene therapy
• No concurrent prophylactic colony-stimulating factors

Chemotherapy

• At least 4 weeks since prior low-dose weekly chemotherapy as a radiosensitizer
• No other prior chemotherapy for NSCLC
• No concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• 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

Surgery

• Not specified

Other

• 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

Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting

Study chairs or principal investigators

Alex A. Adjei, MD, PhD,  Study Chair,  Mayo Clinic Cancer Center   
Kendrith M. Rowland, MD,  Carle Foundation Hospital - Carle Cancer Center   
Julian Molina, MD, PhD,  Mayo Clinic Cancer Center   

Study ID Numbers:  CDR0000398203; NCCTG-N0326; NCT00098540
Record last reviewed:  January 2005
Last Updated:  February 4, 2005
Record first received:  December 7, 2004
ClinicalTrials.gov Identifier:  NCT00098540
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08