This phase II trial studies how well sorafenib tosylate works in treating patients with medullary thyroid cancer that has spread to other parts of the body (metastatic), spread to the tissue surrounding the thyroid (locally advanced), or has returned after a period of improvement (recurrent). Sorafenib tosylate 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.
PRIMARY OBJECTIVES: I. To assess objective response rate of sorafenib tosylate (sorafenib \[BAY 43-9006\]) in metastatic medullary thyroid carcinoma in setting of inherited tumor syndromes, such as multiple endocrine neoplasia (MEN) 2A, MEN 2B, or familial medullary thyroid carcinoma (FMTC). II. To assess objective response rate of sorafenib (BAY 43-9006) in sporadic metastatic medullary thyroid carcinoma. SECONDARY OBJECTIVES: I. To assess toxicity of sorafenib (BAY 43-9006) in patients with metastatic medullary thyroid carcinoma. II. Measure serum tumor markers calcitonin and carcinoembryonic antigen (CEA) pre-, during, and post-treatment to correlate with disease response. III. Correlate nuclear medicine functional imaging (fludeoxyglucose F 18 \[F-18 fluorodeoxyglucose\] positron emission tomography \[PET\] scan) data obtained at pre-, during, and post-treatment with tumor response. IV. Correlate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data obtained at pre-, during, and post-treatment with changes in tumor permeability and vascularity with tumor response. V. Perform pharmacogenomic studies on procured peripheral blood mononuclear cells (PBMCs) if clinical responses are observed. VI. To correlate between the degree of retrovirus-associated sequence (Ras)-mitogen-activated protein kinase (MAPK) signaling inhibition and vascular endothelial growth factor (VEGF) expression in the tumor and clinical response. VII. To correlate between the presence and type of ret proto-oncogene (RET) gene defects in tumor and clinical response. OUTLINE: Patients receive sorafenib tosylate orally (PO) twice daily (BID) in the absence of disease progression or unacceptable toxicity.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
21
Given PO
Washington University School of Medicine
St Louis, Missouri, United States
Duke University Medical Center
Durham, North Carolina, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Objective Response Rate of Sorafenib Tosylate in Metastatic Medullary Thyroid Carcinoma in Setting of Inherited Tumor Syndromes as Well as in Setting of Sporadic Medullary Thyroid Cancer
Measured using MRI scans. Determined using Response Evaluation Criteria in Solid Tumors/World Health Organization response criteria. 95% confidence interval will be calculated to estimate the frequency of response.
Time frame: Up to 4 weeks after last dose of sorafenib tosylate
Number of Patients With Decreased Calcitonin Levels
Identifying the number of patients with decreased calcitonin levels
Time frame: Up to 4 weeks after last dose of sorafenib tosylate
Patient With Decreased Carcinoembryonic Antigen (CEA) Levels
Identify the number of patients with decreased Carcinoembryonic Antigen (CEA) levels
Time frame: Up to 4 weeks after last dose of sorafenib tosylate
Percent of Baseline Dynamic-Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) Exchange Rate Constant (Kep)
Median decrease in exchange rate Kep in index lesions
Time frame: Up to 4 weeks after last dose of sorafenib tosylate
Degree of Ras-MAPK Signaling Inhibition in the Tumor
Identify the number of patients with degree of Ras-MAPK signaling inhibition
Time frame: Up to 4 weeks after last dose of sorafenib tosylate
Degree of Vascular Endothelial Growth Factor (VEGF) Expression in the Tumor
Correlated with clinical response.
Time frame: Up to 4 weeks after last dose of sorafenib tosylate
Standardized Uptake Value (SUV Max) as Measured by Fludeoxyglucose F-18 Positron Emission Tomography (PET)
Identify the median SUV at baseline and 8 week follow up as measured by Fludeoxyglucose F-18 Positron Emission Tomography (PET).
Time frame: Up to 4 weeks after last dose of sorafenib tosylate
Number of Patients With Toxicity, Graded Using the Revised National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0
Toxicities were graded for patients using the revised National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Time frame: Up to 4 weeks after last dose of sorafenib tosylate
Number of Participants With Ret Proto-Oncogene (RET) Gene Defects in the Tumor
Percent of patients with RET mutations
Time frame: Baseline
Selected Polymorphisms of Genes Influencing Sorafenib Tosylate Metabolism and/or Resistance Genes That May Predict Response or Toxicity
Changes will be correlated with toxicity and clinical response to therapy.
Time frame: Baseline
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