BAY 43-9006 (Sorafenib) to Treat Relapsed Non-Small Cell Lung Cancer

NCT00098254 | Completed Phase 2 Results

• 2 other identifiers: 05004905-C-0049
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate the effects and side effects of BAY 43-9006 in patients with advanced, recurrent, or refractory non-small cell lung cancer (NSCLC). BAY 43-9006 is one of a new class of anticancer agents known as bi-aryl ureas. Patients 18 years of age and older with NSCLC that has recurred or progressed after one regimen of chemotherapy may be eligible for this study. Candidates are screened with a medical history and physical examination; blood tests; tumor biopsy (see below); chest x-ray; electrocardiogram; and imaging studies, including positron emission tomography-computed tomography (PET-CT, see below) and dynamic, contrast-enhanced MRI (DCE-MRI, see below). Participants take BAY 43-9006 by mouth twice a day, morning and evening. On the first and 15th days of treatment, patients are admitted to the hospital for pharmacokinetic studies; that is, a test of how the body handles the drug. For the test, blood is collected at intervals (at 15 minutes, 30 minutes, and 1, 2, 4, 6, 8, 12 and 24 hours after ingestion) to determine the drug's level in the bloodstream. Treatment with BAY 43-9006 continues until the study doctor determines that the medication is not beneficial or the patient wishes to withdraw from the study. In addition to drug therapy, patients undergo the following tests and procedures:

• Physical examination every 4 weeks
• Blood pressure checks once a week during the first 4 weeks
• Blood tests every week
• CT scans or other imaging tests, such as ultrasound or MRI, every 8 weeks to evaluate the tumor's response to treatment. CT is an x-ray test that provides detailed pictures of the inside of the body. It can be done from different angles, providing a 3-dimensional picture of the part of the body being studied and allowing the doctor to see the location, nature, and extent of disease. MRI uses a powerful magnet and radio waves instead of x-rays to produce accurate, detailed pictures of organs and tissues.
• PET-CT approximately every 8 weeks to look at how different parts of the body take up and use glucose (a sugar nutrient). Because rapidly growing cells, such as tumors, use more sugar than normal cells do, this test can be used to detect cancer. For the test, the patient is given an injection of a sugar solution in which a radioactive tracer has been attached to the sugar molecule. A special camera detects the radiation emitted by the solution, and the resulting images show how much sugar is being used in various parts of the body. PET-CT uses the PET scan in combination with standard CT in a machine that does both tests.
• DCE-MRI after 2 weeks of treatment. This test uses MRI with a special non-radioactive dye to examine blood flow in a certain part of the body.
• Tumor biopsy (optional) after 2 weeks of treatment. A biopsy is the surgical removal of a small piece of tissue. The tumor biopsy is done either using a small bore needle under CT guidance or by direct visualization using a laparoscope/thoracoscope. For the needle biopsy, a needle is inserted through the skin and guided by CT into the tumor mass. For the laparoscopy/thoracoscopy, the patient is sedated or asleep and small lighted tubes are inserted into small holes made in the skin. The tumor is located and tissue withdrawn.

Conditions

Non-Small-Cell Lung Carcinoma

Keywords

Non-Small Cell; Molecular; Targeted; Therapies; Cancer; Non-Small Cell Lung Cancer; NSCLC

Outcome Measures

Primary Outcomes (3)

• Response Rate

  Percentage of participants with response rate = CR + PR. Response will be evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR (complete response) is the disappearance of all target lesions; PR (partial response) is a 30% decrease in the sum of the longest diameter of target lesions; PD (progressive disease) is a 20% increase in the sum of the longest diameter of target lesions; and SD (stable disease) are small changes that do not meet the above criteria. Please see the Protocol Link module for additional information about RECIST if desired.

  17 months

• Progression Free Survival

  Time between the first day of treatment to the day of disease progression. Progressive disease is at least a 20% increase in the sum of the longest diameter of target lesions. Appearance of one or more new lesions and/or unequivocal progressions of existing non-target lesions.

  17 months

• The Number of Participants With Adverse Events

  Here are the total number of participants with adverse events. For the detailed list of adverse events see the adverse event module.

  5 1/2 years

Secondary Outcomes (13)

• Overall Survival

  17 months

• Percent of Participants With Genotyping of CYP3A4/5 and 5 Polymorphisms

  58 months

• Overall Survival Reported Separately for Participants With a Change in PLGF Below 11 pg/ml and Above 12 pg/ml

  17 months

• Cytokine Levels

  54 days

• Correlation of Response to Treatment With KRAS Mutational Status

  42 months

Study Arms (1)

BAY 43-9006 (Sorafenib)

EXPERIMENTAL

Self administered oral doses at 400 mg twice a day with 250 ml (8 oz.) of water each morning and evening (i.e., 12-hourly) continuously in a 28 day cycle. Tablets may be taken with or without food.

Drug: BAY 43-9006 (Sorafenib)

Interventions

BAY 43-9006 (Sorafenib) DRUG

Self administered oral doses at 400 mg twice a day with 250 ml (8 oz.) of water each morning and evening (i.e., 12-hourly) continuously in a 28 day cycle. Tablets may be taken with or without food.

Also known as: Sorafenib tosylate

BAY 43-9006 (Sorafenib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically documented Non-small cell lung cancer and confirmed by the Laboratory of Pathology at the Clinical Center/National Institutes of Health (NIH) or the Laboratory of Pathology at National Naval Medical Center (NNMC).
• Recurrent or progressed Non-Small Cell Lung Cancer (NSCLC).
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than 20 mm with conventional techniques or as greater than 10 mm with spiral Computed tomography (CT) scan.
• Patients must have recovered from toxicity related to prior therapy to at least to grade 1 (defined by Common Terminology Criteria for Adverse Events (CTCAE) 3.0) and must not have had prior chemotherapy within 4 weeks. Patients must be at least 28 days since any prior radiation or major surgery.
• Age greater than 18 years (males or non-pregnant females). Because no dosing or adverse event data are currently available on the use of BAY 43-9006 in patients less than 18 years of age, children are excluded from this study but will be eligible for future pediatric single-agent trials, if applicable.
• Life expectancy of greater than 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status less than 2 (Karnofsky \> 60%).
• Patients must have adequate organ and marrow function (as defined below). Patients must have returned to base line or grade one from any acute toxicity related to prior therapy.
• Leukocytes greater than 3,000/micro l;
• Absolute neutrophil count greater than 1,200/micro l;
• Platelets greater than 100,000/micro l;
• International normalized ratio (INR) less than or equal to 1.2
• Partial thromboplastin time (PTT) less than or equal to 36 seconds or abnormality can be explained by the presences of lupus anticoagulant
• Total bilirubin less than or equal to 1.5 times the institutional upper limits of normal;
• Aspartate aminotransferase, oxaloacetic transaminase (AST,SGOT) and alanine transaminase, serum glutamic pyruvic transaminase (ALT,SGPT) less than 2.5 times the institutional upper limits of normal;

You may not qualify if:

• Patients with symptomatic brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. However, patients who have had treatment for their brain metastases and whose brain metastatic disease status has remained stable for at least 3 months without steroids may be enrolled at the discretion of the principal investigator.
• Uncontrolled medical illness including, but not limited to, ongoing or uncontrolled, symptomatic congestive heart failure (American Heart Association (AHA) Class II or worse), uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Human immunodeficiency virus (HIV)positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with BAY 43-9006. HIV positive patients not receiving antiretroviral therapy are excluded due to the possibility that BAY 43-9006 may worsen their condition and the likelihood that the underlying condition may obscure the attribution of adverse events with respect to BAY 43-9006.
• Patients may not be receiving any other investigational agents.
• History of another invasive malignancy in the last five years. Non-invasive, non-melanoma skin cancers will be allowed.
• Patients with conditions that would impair their ability to swallow tablets are excluded.
• Patients must not have any evidence of bleeding diathesis.
• Patients must not be on therapeutic anticoagulation. Prophylactic anticoagulation (i.e. low dose warfarin) of venous or arterial access devices is allowed provided that the requirements for prothrombin time (PT), international normalized ratio (INR) or partial thromboplastin time (PTT) are met.
• Both men and women and members of all races and ethnic groups are eligible for this trial. Every effort will be made to recruit women and minorities in this study.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. doi: 10.1056/NEJMoa011954.

  PMID: 11784875 BACKGROUND

• Scagliotti GV, De Marinis F, Rinaldi M, Crino L, Gridelli C, Ricci S, Matano E, Boni C, Marangolo M, Failla G, Altavilla G, Adamo V, Ceribelli A, Clerici M, Di Costanzo F, Frontini L, Tonato M; Italian Lung Cancer Project. Phase III randomized trial comparing three platinum-based doublets in advanced non-small-cell lung cancer. J Clin Oncol. 2002 Nov 1;20(21):4285-91. doi: 10.1200/JCO.2002.02.068.

  PMID: 12409326 BACKGROUND

• Choy H, Devore RF 3rd, Hande KR, Porter LL, Rosenblatt P, Yunus F, Schlabach L, Smith C, Shyr Y, Johnson DH. A phase II study of paclitaxel, carboplatin, and hyperfractionated radiation therapy for locally advanced inoperable non-small-cell lung cancer (a Vanderbilt Cancer Center Affiliate Network Study). Int J Radiat Oncol Biol Phys. 2000 Jul 1;47(4):931-7. doi: 10.1016/s0360-3016(00)00420-x.

  PMID: 10863062 BACKGROUND

• Kelly RJ, Rajan A, Force J, Lopez-Chavez A, Keen C, Cao L, Yu Y, Choyke P, Turkbey B, Raffeld M, Xi L, Steinberg SM, Wright JJ, Kummar S, Gutierrez M, Giaccone G. Evaluation of KRAS mutations, angiogenic biomarkers, and DCE-MRI in patients with advanced non-small-cell lung cancer receiving sorafenib. Clin Cancer Res. 2011 Mar 1;17(5):1190-9. doi: 10.1158/1078-0432.CCR-10-2331. Epub 2011 Jan 11.

  PMID: 21224376 RESULT

Related Links

• NIH Clinical Center Detailed Web Page
• Medline Plus
• Drug Information
• US FDA Resources
• RECIST

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Giuseppe Giaccone, M.D., PH.D.
• Organization: National Cancer Institute

giacconeg@mail.nih.gov

301-496-4916

Study Officials

• Giuseppe Giaccone, M.D., Ph.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: December 3, 2004
• First Posted: December 6, 2004
• Study Start: December 1, 2004
• Primary Completion: November 1, 2009
• Study Completion: January 1, 2011
• Last Updated: May 2, 2012
• Results First Posted: May 2, 2012

Record last verified: 2012-04

Locations

US (1)