Neoplasms

All Conditions

Symptoms and General Pathology

Gland and Hormone Related Diseases

Diseases and Abnormalities at or Before Birth

Rare Diseases

Carcinoma

Recurrence

Thyroid Neoplasms

Thyroid Diseases

Endocrine Gland Neoplasms

Carcinoma, Medullary

Multiple Endocrine Neoplasia

Multiple Endocrine Neoplasia Type 2a

Multiple Endocrine Neoplasia Type 2b

Carcinoma, Neuroendocrine

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endocrine System Diseases

Neuroendocrine Tumors

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Adenocarcinoma

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Head and Neck Neoplasms

Neoplasms, Multiple Primary

Syndrome

Neoplastic Syndromes, Hereditary

Genetic Diseases, Inborn

Thyroid Cancer, Medullary

Multiple Endocrine Neoplasia Type 2

Multiple Endocrine Neoplasia Type 2A

Multiple Endocrine Neoplasia Type 2B

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Sorafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

Patients receive sorafenib tosylate PO BID in the absence of disease progression or unacceptable toxicity.

Sorafenib Tosylate

Bhavana Konda

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.

Sorafenib Tosylate in Treating Patients With Metastatic, Locally Advanced, or Recurrent Medullary Thyroid Cancer

Phase II Study of Sorafenib (BAY 43-9006) in Patients With Metastatic Medullary Thyroid Carcinoma

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.

Identifying the number of patients with decreased calcitonin levels

Identify the number of patients with decreased Carcinoembryonic Antigen (CEA) levels

Median decrease in exchange rate Kep in index lesions

Identify the number of patients with degree of Ras-MAPK signaling inhibition

Identify the median SUV at baseline and 8 week follow up as measured by Fludeoxyglucose F-18 Positron Emission Tomography (PET).

Toxicities were graded for patients using the revised National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0

Changes will be correlated with toxicity and clinical response to therapy.

National Cancer Institute (NCI)

The National Cancer Institutes Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for adverse event reporting

Arm A:

Sorafenib (BAY 43-9006) was administered at the dose of 400 mg orally twice a day on a continuous basis.

Arm B:

Sorafenib (BAY 43-9006) was administered at the dose of 400 mg orally twice a day on a continuous basis.

Arm A (Hereditary MTC) and Arm B (Sporadic MTC)

Sorafenib (BAY 43-9006) was administered at the dose of 400 mg orally twice a day on a continuous basis.

Arm A (Hereditary MTC)

Arm B (Sporadic MTC)

Total

Age, Categorical

Sex: Female, Male

White

Nonwhite

Race/Ethnicity, Customized

United States

Region of Enrollment

Manisha Shah, MD

1 patient was not evaluable for RECIST evaluation in Arm B

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

Arm A:

Sorafenib (BAY 43-9006) was administered at the dose of 400 mg orally twice a day on a continuous basis.

Arm B:

Sorafenib (BAY 43-9006) was administered at the dose of 400 mg orally twice a day on a continuous basis.

Number of Patients With Decreased Calcitonin Levels

Patient With Decreased Carcinoembryonic Antigen (CEA) Levels

Percent of Baseline Dynamic-Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) Exchange Rate Constant (Kep)

Due to low tumor cellularity in the samples obtained, such evaluation was not possible

Degree of Ras-MAPK Signaling Inhibition in the Tumor

MTC in setting of inherited syndromes (MEN-2A, 2B or FMTC) plus Measurable disease Plus No prior ZD6474 or AMG 706

Arm A

MTC in setting of sporadic ds plus Measurable disease Plus No prior ZD6474 or AMG 706

Spots Global Cancer Trial Database for hereditary thyroid gland medullary carcinoma