Sorafenib Treatment in Non-Small Cell Lung Cancer After Failure of Epidermal Growth Factor Receptor-tyrosine Kinase Inhibitor

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00922584
Recruitment Status : Completed
First Posted : June 17, 2009
Last Update Posted : August 21, 2013
Information provided by (Responsible Party):
Yi-Long Wu, Chinese Society of Lung Cancer

Brief Summary:
This trial's aim is to evaluate the efficacy and toxicity of sorafenib in relapsed advanced Non-Small Cell Lung Cancer (NSCLC) after failure of epidermal growth factor receptors-tyrosine kinase inhibitor (EGFR-TKI) treatment and to explore the correlation between clinical outcomes and biochemical modulation of signal transduction pathways.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: sorafenib (Nexavar) Phase 2

Detailed Description:
Sorafenib, an oral multi-kinase inhibitor, targets the Raf/MEK/ERK pathway at the level of Raf kinase and VEGF receptor tyrosine kinases, and has shown efficacy against NSCLC in Phase I/II trials. Because the targets of sorafenib are different from that of EGFR-TKI, it is reasonable for sorafenib to treat relapsed advanced NSCLC after failure of EGFR-TKI treatment.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 65 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Sorafenib (BAY 43-9006®) in Patients With Relapsed Advanced Non-Small Cell Lung Cancer(NSCLC) After Failure of Epidermal Growth Factor Receptor-tyrosine Kinase Inhibitor (EGFR-TKI)Treatment
Study Start Date : December 2008
Actual Primary Completion Date : January 2012
Actual Study Completion Date : April 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: sorafenib
Patients with stage IIIB/IV NSCLC who failed EGFR-TKI therapy will receive oral sorafenib 400 mg twice daily until disease progression or unacceptable toxicity.
Drug: sorafenib (Nexavar)
oral sorafenib 400 mg, twice daily, until disease progression or unacceptable toxicity

Primary Outcome Measures :
  1. Disease control rate (CR+PR+SD) [ Time Frame: 1 year ]

Secondary Outcome Measures :
  1. Response duration [ Time Frame: 2 years ]
  2. time-to-progression [ Time Frame: 2 years ]
  3. progression free survival [ Time Frame: 2 years ]
  4. overall survival [ Time Frame: 2 years ]
  5. safety profile [ Time Frame: 2 years ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histological or cytological documented stage IIIB (not amenable for radical regional therapy) or stage IV NSCLC. The pathological diagnosis must be adenocarcinoma with or without bronchioalveolar carcinoma. Sputum cytology alone is excluded.
  • Recurrent or progressive disease after prior one EGFR-TKI treatment. The patient must have stopped the EGFR-TKI treatment for at least two weeks. The response to EGFR-TKI should be partial response or complete response or stable disease (the duration of stable disease should be more than 3 months). Patients who had never received chemotherapy or received one regimen chemotherapy before EGFR-TKI are eligible.
  • Prior surgery, including palliative surgery, is permitted if performed 4 weeks before the start of study treatment and the patient is fully recovered.
  • Prior localized radiotherapy 4 weeks before the start of study is permitted if it was not administered to target lesions selected for this study, unless progression of the selected target lesions within the radiation portal is documented. Patient has recovered from CTCAE grade 3/4 toxicity of radiotherapy. Palliative radiotherapy within 4 weeks of start of study is also permitted.
  • Age > 18 years.
  • ECOG Performance Status of 0, 1,or 2. Life expectancy of at least 3 months. Measurable disease, according to the RECIST, the presence of at least one uni-dimensional measurable lesion with longest diameter > 20 mm by conventional techniques or > 10 mm by spiral CT scan.
  • Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:
  • Hemoglobin > 9.0 g/dl
  • Platelet count > 75x109/L
  • Total bilirubin ≤ 1.5 x upper limit of normal
  • ALT and AST < 2.5 x upper limit of normal without liver metastasis, ALT and AST < 5 x upper limit of normal with liver metastasis.
  • International normalized ratio (INR) ≤ 1.5 x the upper limit of normal and prothrombin time (PT) ≤ 1.5 x the upper limit of normal. Patients who are being therapeutically anticoagulated with an agent such as Coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.
  • Serum creatinine < 1.5 x upper limit of normal.

Exclusion Criteria:

  • Patients who are currently enrolled in, are eligible for, or have access to, any other sorafenib clinical trial.
  • Mixed small cell and non-small cell lung cancer histology. Other pathological types of NSCLC than adenocarcinoma and bronchioloalveolar cell carcinoma.
  • Failure of EGFR-TKI is due to toxicity.
  • Prior with exposure to biotherapy, immunotherapy within 4 weeks of study entry.
  • Prior exposure to sorafenib or other agents targeting the Ras/MARK pathway or VEGFR.
  • Any unresolved toxicity more than CTCAE grade 2 from previous anti-cancer therapy.
  • Patients with cardiac arrhythmias greater than grade 1 NCI CTCAE, Version 3.0(Conduction abnormality and supraventricular arrhythmia present but patient is asymptomatic; intervention not indicated, palpitations present and QTC > 0.45-0.47 second); however, patients with grade 2 atrial fibrillation may be included.
  • Significant cardiovascular event: congestive heart failure > NYHA class 2; unstable angina, active CAD (myocardial infarction more than 6 months prior to study entry is allowed); serious cardiac arrhythmia requiring anti-arrythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension.
  • Any disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of any study medication (sorafenib) or that might affect the interpretation of the results or render the subject at high risk from treatment.
  • Central nervous system (CNS) tumor or metastatic tumor.
  • Clinically significant gastrointestinal bleeding within 30 days of study entry.

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00922584

China, Guangdong
Guangzhou, Guangdong, China, 510080
Sponsors and Collaborators
Chinese Society of Lung Cancer
Principal Investigator: Wu Yi Long, Professor Guangdong General Hospital

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Yi-Long Wu, Director of Chinese Society of Lung Cancer/Chief of Lung Cancer Research Institute & Cancer Center/Vice President of Guangdong General hospital, Chinese Society of Lung Cancer Identifier: NCT00922584     History of Changes
Other Study ID Numbers: C-TONG0805
First Posted: June 17, 2009    Key Record Dates
Last Update Posted: August 21, 2013
Last Verified: August 2013

Keywords provided by Yi-Long Wu, Chinese Society of Lung Cancer:
non-small cell lung cancer
targeted therapy

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs
Mitosis Modulators