Study of Everolimus and Sorafenib in Patients With Advanced Thyroid Cancer Who Progressed on Sorafenib Alone

Study Overview
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Brief Summary
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The goal of this study is to determine the effect of combining everolimus and sorafenib in patients with metastatic differentiated thyroid cancer who progressed on sorafenib alone.

Detailed Description
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The purpose of this research study is to: Find out if sorafenib and everolimus prevent the growth of tumors that have grown when treated with sorafenib alone Find out how long one might benefit from treatment with sorafenib and everolimus Find out what side effects this drug may cause Measure the amount of sorafenib and everolimus in the blood and see if markers can be found to help understand who might benefit from sorafenib and everolimus.

Official Title
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A Phase II Study of Everolimus and Sorafenib in Patients With Metastatic Differentiated Thyroid Cancer Who Have Progressed on Sorafenib Alone

Conditions
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Differentiated Thyroid Cancer

Intervention / Treatment
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* Drug: Everolimus
* Drug: Sorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of thyroid cancer, that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. All patients will have been required to have had sorafenib for entry and have had documented progression while on previous treatment with sorafenib. Measurable disease defined as at least one malignant lesion that can be accurately measured on computerized tomography (CT) and/or magnetic resonance imaging (MRI) scan. ECOG performance status < 2. Life expectancy greater than 3 months. Intellectual, emotional, and physical ability to comply with oral medication. Exclusion Criteria: Restrictions regarding certain prior treatments will apply. 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 high dose corticosteroid treatment (Topical or inhaled corticosteroids are allowed); requirement for concurrent immunosuppressive drug(s); active autoimmune disease. Organ allografts. Known HIV-infection (HIV testing is not required for participation). Pregnant or breast feeding. 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 treated cervical cancer, colon cancer or melanoma, or any other cancer for which the patient has been disease-free for three or more years). Known hypersensitivity to everolimus or other rapamycins (e.g., sirolimus, temsirolimus) or to its excipients Use of any experimental therapy within 4 weeks prior to baseline evaluations done prior to enrollment (with the exception of sorafenib which may be continued until treatment start). Therefore, all experimental treatments other than sorafenib must be discontinued 4 weeks prior to baseline studies or enrollment. Patients who did not previously tolerate sorafenib at 200 mg once daily are excluded from the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 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: Everolimus and sorafenib<br>All patients will receive everolimus and sorafenib daily. | Drug: Everolimus<br>* One 5 mg. tablet daily.<br>* Other names: Afinitor;Drug: Sorafenib<br>* 200 mg. twice daily.<br>* Other names: Nexavar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the efficacy of everolimus and sorafenib (progression free survival, objective response rate and stable disease) in patients with advanced differentiated thyroid cancer who have progressed on sorafenib alone. |  | Every 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the secondary endpoints of best response in patients receiving everolimus and sorafenib. |  | Every 4 weeks | 
| To perform correlative scientific studies to determine the relationship between clinical response to everolimus and sorafenib and multiple parameters including the mutational status of BRAF, N-RAS and other relevant cancer genes in the tumor. |  | Every 4 weeks | 
| To investigate the effectiveness of mTOR and Raf kinase inhibition in surrogate tissue and tumor samples. |  | Every 4 weeks | 
| To evaluate the activity of additional signaling pathways in surrogate tissue and tumor samples and explore their relevance to outcome measures. |  | Every 4 weeks | 
| To evaluate the secondary endpoints of time to disease progression in patients receiving everolimus and sorafenib. |  | Every 4 weeks | 
| To evaluate the secondary endpoints of duration of response in patients receiving everolimus and sorafenib. |  | Every 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Differentiated metastatic thyroid cancer