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

Study Overview
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Brief Summary
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Phase II trial to study the effectiveness of sorafenib tosylate in treating patients who have locally advanced, metastatic, or locally recurrent thyroid cancer. Sorafenib tosylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth and by stopping blood flow to the tumor.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine objective response rate in patients with locally advanced, metastatic, or locally recurrent differentiated thyroid cancer treated with sorafenib (BAY 43-9006). SECONDARY OBJECTIVES: I. Determine the toxicity of this drug in these patients. II. Correlate thyroglobulin levels with tumor response in patients treated with this drug. III. Correlate fludeoxyglucose F 18 positron emission tomography results with tumor response in patients treated with this drug. IV. Correlate tumor permeability and vascularity, as determined by dynamic contrast-enhanced MRI, with tumor response in patients treated with this drug. V. Determine the pharmacodynamics of this drug in these patients. VI. Correlate the presence and type of B-raf, N-ras, or RET/PTC gene mutations with clinical response in patients treated with this drug. VII. Correlate the degree of Ras-MAPK signaling inhibition and vascular endothelial growth factor expression with clinical response in patients treated with this drug. OUTLINE: This is a multicenter study. Patients are stratified according to diagnosis (papillary thyroid cancer that is chemo-naïve vs all others). Patients receive oral sorafenib tosylate twice daily for up to 6 months in the absence of disease progression or unacceptable toxicity. Patients achieving complete remission (CR) receive 8 additional weeks of therapy beyond CR. Patients are followed within 2-4 weeks after completion of study treatment.

Official Title
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Phase II Study of BAY 43-9006 in Patients With Metastatic Thyroid Carcinoma

Conditions
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Anaplastic Thyroid Cancer, Insular Thyroid Cancer, Recurrent Thyroid Cancer, Stage III Follicular Thyroid Cancer, Stage III Papillary Thyroid Cancer, Stage IV Follicular Thyroid Cancer, Stage IV Papillary Thyroid Cancer

Intervention / Treatment
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* Drug: sorafenib tosylate
* Other: laboratory biomarker analysis
* Other: pharmacological study
* Radiation: fludeoxyglucose F 18
* Procedure: positron emission tomography
* Procedure: dynamic contrast-enhanced magnetic resonance imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of 1 of the following: Papillary thyroid cancer (stratum I) Papillary, follicular, Hurthle cell, insular, or anaplastic thyroid cancer (stratum II) Mixed histology, poorly differentiated, or tall-cell variants allowed Metastatic, locally advanced, or locally recurrent disease At least 1 unidimensionally measurable lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan The following are considered non-measurable disease: Tumors in a previously irradiated area Bone lesions Leptomeningeal disease Ascites Pleural/pericardial effusion Lymphangitis cutis/pulmonis Abdominal masses not confirmed and followed by imaging techniques Cystic lesions Archival tumor tissue block OR material collected before study entry available (stratum I) Biopsy-accessible disease (stratum I) Performance status - ECOG 0-1 At least 6 months WBC >= 3,000/mm^3 Absolute neutrophil count >= 1,500/mm^3 Platelet count >= 100,000/mm^3 No bleeding diathesis Bilirubin =< 1.5 times upper limit of normal (ULN) AST and ALT =< 1.5 times ULN Creatinine =< 1.5 times ULN No uncontrolled hypertension Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Willing to undergo 2 tumor biopsies during study participation (stratum I) No history of allergic reaction attributed to compounds of similar chemical or biologic composition to sorafenib No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance No other uncontrolled illness No other concurrent malignancy except nonmetastatic nonmelanoma skin cancer or carcinoma in situ of the cervix No prior systemic chemotherapy for thyroid cancer (stratum I) Prior systemic chemotherapy used to treat a second primary cancer with curative intent allowed provided the primary cancer was treated more than 5 years before study entry No more than 3 prior systemic chemotherapy regimens for thyroid cancer (stratum II) More than 6 weeks since prior systemic chemotherapy (stratum II) No prior external beam radiotherapy to the sole site of measurable disease (except for patients with anaplastic thyroid cancer) More than 6 weeks since prior external beam radiotherapy More than 24 weeks since prior iodine I 131 Recovered from all prior therapy No prior sorafenib More than 6 weeks since prior investigational tumor-specific therapy Concurrent oral or IV bisphosphonates for bony metastases allowed at the discretion of the investigator No other concurrent tumor-specific or investigational therapy No concurrent combination antiretroviral therapy for HIV-positive patients No concurrent therapeutic anticoagulation Concurrent prophylactic anticoagulation (e.g., low-dose warfarin) for venous or arterial access devices allowed provided PT, INR, or PTT are normal

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (sorafenib tosylate)<br>Patients receive oral sorafenib tosylate twice daily for up to 6 months in the absence of disease progression or unacceptable toxicity. Patients achieving CR receive 8 additional weeks of therapy beyond CR. | Drug: sorafenib tosylate<br>* Given PO<br>* Other names: SFN;Other: laboratory biomarker analysis<br>* Correlative studies<br>Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;Radiation: fludeoxyglucose F 18<br>* Correlative studies<br>* Other names: FDG;Procedure: positron emission tomography<br>* Correlative studies<br>* Other names: tomography, emission computed;Procedure: dynamic contrast-enhanced magnetic resonance imaging<br>* Correlative studies<br>* Other names: DCE-MRI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | The 95% confidence intervals should be provided. | Up to 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of toxicity |  | Up to 4 weeks |