Phase II Study of Sorafenib (BAY 43-9006) in Patients With Metastatic Medullary Thyroid Carcinoma
I. Determine objective response rate in patients with metastatic, locally advanced, or
recurrent medullary thyroid carcinoma in a setting of inherited tumor syndromes, such as
multiple endocrine neoplasia (MEN) 2A, MEN 2B, or familial medullary thyroid carcinoma
(FMTC), treated with sorafenib tosylate.
II. Determine objective response rate in patients with sporadic metastatic medullary thyroid
carcinoma treated with sorafenib tosylate.
I. Determine toxicity of sorafenib in these patients.Measure serum tumor markers calcitonin
and carcinoembryonic antigen (CEA) pre-, during, and post-treatment and correlate with
disease response in these patients.
II. Correlate nuclear medicine functional imaging (fludeoxyglucose F 18 positron emission
tomography [PET] scan) data obtained at pre-, during, and post-treatment with tumor response
in these patients.
III. Correlate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data obtained
at pre-, during, and post-treatment with changes in tumor permeability and vascularity and
tumor response in these patients.
IV. Perform pharmacogenomic studies on procured peripheral blood mononuclear cells (PBMCs)
if clinical responses are observed in these patients.
V. Correlate the degree of Ras-MAPK signaling inhibition with vascular endothelial growth
factor (VEGF) expression in the tumor and clinical response in these patients.
VI. Correlate the presence and type of RET gene defects in tumor with clinical response in
OUTLINE: This is a multicenter study. Patients are stratified according to clinical setting
of disease (inherited tumor syndromes vs sporadic).
Patients receive oral sorafenib tosylate twice daily on days 1-56. Treatment repeats every 8
weeks in the absence of disease progression or unacceptable toxicity.
Patients undergo blood collection and tumor biopsies for biomarker/laboratory studies
(immunohistochemistry, pharmacogenomic studies, and genotyping) at baseline, every 8 weeks
during treatment, and after completion of study treatment. Tumor markers may include
carcinoembryonic antigen (CEA), calcitonin, and RET mutations.
After completion of study treatment, patients are followed for 4 weeks.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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 RECIST/WHO response criteria. 95% confidence interval will be calculated to estimate the frequency of response.
Every 12 weeks
Ohio State University
United States: Food and Drug Administration
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