Clinical trial NCT00754923: Sorafenib in Treating Non-Smokers or Former Light Smokers With Relapsed or Refractory Stage IIIB or Stage IV Non-Small Cell Lung Cancer
Official title: A Phase II Study of Single Agent Sorafenib in Non-small Cell Lung Cancer Patients Who Never Smoked or Were Former Light Smokers.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: 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
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2008-09-18
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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 criteria: 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

Primary outcomes:
measure: Progression-free Survival at 6 Months
timeFrame: 6 months
Secondary outcomes:
measure: Overall Survival Rate
timeFrame: Up to 2 years
measure: Incidence of Adverse Events Sssessed by Common Terminology Criteria for Adverse Events (CTCAE)
timeFrame: Up to 2 years
measure: Mutational Status for EGFR or Kras
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
Study officials:
affiliation: Ohio State University
name: Miguel A. Villalona, MD
role: PRINCIPAL_INVESTIGATOR
References: