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

• ClinicalTrials.gov Identifier: NCT00754923
• Recruitment Status: Terminated
• First Posted: September 18, 2008
• Results First Posted: June 4, 2014
• Last Update Posted: March 6, 2019
• Sponsor: Ohio State University Comprehensive Cancer Center
• Collaborator: Bayer
• Information provided by (Responsible Party): Ohio State University Comprehensive Cancer Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Lung Cancer	Drug: sorafenib	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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.
• Actual Study Start Date: October 2008
• Actual Primary Completion Date: April 2012
• Actual Study Completion Date: April 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment: Sorafenib; Sorafenib will be administered at a dose of 400 mg taken twice daily, continuously on a 28 day cycle.	Drug: sorafenib; administered orally at 400 mg taken twice daily , continuously on a 28 day cycle as an outpatient.; Other Names: Nexavar; sorafenib tosylate

Outcome Measures

Primary Outcome Measures :

1. Progression-free Survival at 6 Months [ Time Frame: 6 months ]
   Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions", or similar definition as accurate and appropriate

Secondary Outcome Measures :

1. Overall Survival Rate [ Time Frame: Up to 2 years ]
   Determine the one year survival rate in Non/Light smokers with advanced and previouslytreated NSCLC
2. Incidence of Adverse Events Sssessed by Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: Up to 2 years ]
   Assess the frequency and severity of adverse events associated with Sorafenib in this patient population Non/Light smokers with advanced and previously treated NSCLC.
3. Mutational Status for EGFR or Kras [ Time Frame: up to 2 years ]

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, Ohio

Ohio State University

Columbus, Ohio, United States, 43210-1240

Sponsors and Collaborators

Ohio State University Comprehensive Cancer Center

Bayer

Investigators

• Principal Investigator: Miguel A. Villalona, MD; Ohio State University

More Information

Additional Information:

Jamesline 

• Responsible Party: Ohio State University Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT00754923
• Other Study ID Numbers: OSU-08017; NCI-2011-03192 ( Registry Identifier: Clinical Trial Reporting Program (CTRP) )
• First Posted: September 18, 2008
• Results First Posted: June 4, 2014
• Last Update Posted: March 6, 2019
• Last Verified: February 2019

Keywords provided by Ohio State University Comprehensive Cancer Center:

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

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Sorafenib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action