Patient case: 71-year-old female with lung cancer; genetic feature: ROS1

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

Summary: 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: 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.

Eligibility: 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

Relevance to patient case: not relevant