Phase II Trial of Sorafenib (Nexavar) in Patients With Advanced Thyroid Cancer

Study Overview
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Brief Summary
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The goal of this study is to determine the activity of sorafenib in patients with advanced (metastatic or recurrent) thyroid cancer.

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

Conditions
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Metastatic Differentiated Thyroid Cancer, Metastatic Poorly Differentiated Thyroid Cancer, Metastatic Anaplastic Thyroid Cancer, Metastatic Medullary Thyroid Cancer

Intervention / Treatment
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* Drug: sorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically confirmed thyroid cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. Patients may have received multiple treatments of radioactive iodine, one prior biologic treatment, and at least half of the patients will have had no prior chemotherapy for metastatic disease. At least 3 weeks must have elapsed since prior treatment. Measurable disease defined as at least one malignant lesion that can be accurately and serially measured in at least one dimension (longest diameter to be recorded), using a caliper (diameter > 10 mm) for superficial cutaneous disease, or using contrast-enhanced CT or spiral CT (diameter > 20 mm) for visceral or nodal/soft tissue disease. ECOG performance status < 2 (Appendix 1). Life expectancy greater than 3 months. Adequate organ function that has been determined within 7 days prior to enrollment, defined as:Leucocyte count > 3,000/uL; Absolute neutrophil count (ANC) > 1,500/mm3, platelets > 100,000/mm3, and hemoglobin > 9 g/dl; Serum creatinine < 1.5 times ULN, or 24-hour creatinine clearance > 75 cc/min. (Note: creatinine clearance need not be determined if the baseline serum creatinine is within normal limits); Serum bilirubin < 1.5 times ULN; serum glutamyloxaloacetic transaminase (SGOT) < 2.5 ULN; alkaline phosphatase < 2.5 times ULN; PT-INR/PTT < 1.5 x upper limit of normal. Intellectual, emotional, and physical ability to comply with oral medication. Ability to understand and the willingness to sign a written informed consent Patients with disease accessible for biopsy will be preferentially selected for participation in the study. Accessible disease includes lymph node metastases. Female patients of child-bearing potential must have a negative pregnancy test within 14 days before initiation of study drug dosing. Post-menopausal women must be amenorrheic for at least 12 months to be considered non-child-bearing potential. Male and female patients of reproductive potential must agree to use adequate contraception (i.e. hormonal or barrier method of birth control). throughout the study and for 3 months after the study. Exclusion Criteria: Significant medical disease including: uncontrolled congestive heart failure; active symptoms of coronary artery disease, uncontrolled seizure disorder; active infection; uncontrolled diabetes mellitus; requirement for chronic corticosteroid treatment; requirement for concurrent immunosuppressive drug(s); active autoimmune disease. Organ allografts. Known HIV-infection (HIV testing is not required for participation). Pregnancy or lactation. Women of childbearing potential and sexually active males must be advised to take precautions to prevent pregnancy during treatment History of second cancer (except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for five or more years). Use of any experimental therapy within 3 weeks prior to baseline evaluations done prior to enrollment. Patients with carcinomatous meningitis are excluded from the study. Excluded therapies and medications, previous and concomitant:Anticancer chemotherapy or immunotherapy during the study or within 4 weeks prior to the first dose of the study drug; Radiotherapy for the treatment of a symptomatic (e.g. bone metastasis) as clinically indicated is allowed as long as it is not evidence of progressive disease (see 4.5.2); -Biological response modifiers, such as G-CSF, within 3 week prior to study entry. (G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator; however they may not be substituted for a required dose reduction); Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or during the study; Investigational drug therapy outside of this trial during or within 4 weeks prior the screening assessment; Use of ketoconazole, itraconazole, and ritonavir; Use of carbamazepine, phenytoin, phenobarbital; Previous exposure to a Ras pathway inhibitor (including herceptin, EGFr inhibitors, farnesyl transferase inhibitors or MEK inhibitors); Use of grapefruit juice products; Use of cyclosporin; Pregnant or breast feeding.

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: 1<br>This is a single arm study. | Drug: sorafenib<br>* 400mg PO BID daily<br>* Other names: Nexavar (Bayer);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Determine the Efficacy (Best Response) of BAY 43-9006 (Objective Response Rate and Stable Disease) in Patients With Metastatic Thyroid Carcinoma. | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Progression Free Survival in Patients Receiving BAY 43-9006 (Sorafenib). | This is the result of the Kaplan Meier analysis of all patients treated with sorafenib | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thyroid Cancer, Anaplastic, Medullary, sorafenib