Sorafenib in Treating Patients With Advanced Anaplastic Thyroid Cancer

Study Overview
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Brief Summary
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This phase II trial is studying how well sorafenib works in treating patients with advanced anaplastic thyroid cancer. Sorafenib 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.

Detailed Description
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OBJECTIVES: I. Determine whether the objective response rate is ≥ 20% in patients with advanced anaplastic thyroid cancer treated with sorafenib. II. Determine the survival of patients treated with this drug. III. Determine the safety profile of this drug in these patients. IV. Determine the pharmacokinetic predictors of response to this drug in these patients. OUTLINE: This is a multicenter study. Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed for survival.

Official Title
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Phase II Trial of BAY 43-9006 in Patients With Advanced Anaplastic Carcinoma of the Thyroid

Conditions
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Anaplastic Thyroid Cancer, Recurrent Thyroid Cancer

Intervention / Treatment
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* Drug: sorafenib tosylate


Participation Criteria
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Eligibility Criteria
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Criteria: Progressive disease after prior cytotoxic chemotherapy (i.e., chemotherapy alone or combined with radiotherapy) No symptomatic bulky disease that would impair the airway or impede swallowing (for patients with ECOG performance status 2) No known brain metastases Measurable or evaluable disease Measurable disease, defined as ≥ 1 unidimensionally measurable lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan Measurable disease not in a previously irradiated field Patients with evidence of abnormal cardiac conduction (e.g., bundle branch block or heart block) are eligible provided disease has been stable for the past 6 months Performance status: ECOG 0-2 OR Karnofsky 50-100% Life expectancy more than 8 weeks Absolute neutrophil count >= 1,250/mm3 Platelet count >= 100,000/mm3 No evidence of bleeding diathesis Bilirubin =< 1.5 times upper limit of normal (ULN) PTT =< 1.5 times ULN Creatinine =< 1.5 times ULN No myocardial infarction within the past 6 months No New York Heart Association class III or IV cardiac disease No symptomatic congestive heart failure No unstable angina pectoris No uncontrolled hypertension (i.e., systolic blood pressure (BP) > 150 mm Hg OR diastolic BP > 100 mm Hg) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Able to swallow oral medication No history of allergic reactions attributed to compounds of similar chemical or biological composition to sorafenib No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance No other invasive malignancy within the past 5 years except nonmelanoma skin cancer No other uncontrolled illness No more than 2 prior systemic cytotoxic chemotherapy regimens (combined modality systemic cytoxic chemotherapy is considered 1 prior cytotoxic regimen) At least 7 days since prior chemotherapy and recovered At least 7 days since prior radiotherapy and recovered No prior sorafenib or other inhibitors of MAP kinase signaling intermediates No prior cancer treatment that would preclude study participation No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent investigational agents No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital) No concurrent Hypericum perforatum (St. John's wort) or rifampin No concurrent therapeutic anticoagulation (concurrent prophylactic anticoagulation (i.e., low-dose warfarin) for venous or arterial access devices allowed provided requirements for INR and PTT are met) No other concurrent anticancer therapy Histologically confirmed anaplastic* thyroid cancer Not amenable to definitive curative surgery or radiotherapy [Note: *Papillary, follicular, or other histologies that are mixed or identified in a diagnostic tissue sample are allowed provided a high-grade undifferentiated anaplastic component is present ] No cardiac arrhythmia AST and ALT =< 3.5 times ULN INR < 2.0

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 twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: sorafenib tosylate<br>* Given orally<br>* Other names: SFN;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Response to Treatment Measured by RECIST Criteria | Response evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. The patient's best response depends on the achievement of measurement and confirmation criteria of Complete Response (CR), Stable Disease (SD), Partial Response (PR) or Progressive Disease (PD). Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques (CT, MRI, x-ray) or as >10 mm with spiral CT scan. | at 6 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival Was Measured From the Date of Outset of Treatment to the Date of Disease Progression. |  | 27 months | 
| Overall Survival Was Measured From the Date of Outset of Treatment to the Date of Death. |  | 27 months | 
| Number of Participants That Experienced Adverse Events to Characterize the Safety Profile of BAY 43-9006 | The safety and toxicity profile of BAY 43-9006 as measured by toxicity grades of adverse events. | 27 months |