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

Thomas Jefferson University1 site in 1 country35 target enrollmentNovember 2010

ConditionsDifferentiated Thyroid Cancer

InterventionsEverolimus Sorafenib

DrugsEverolimus Sorafenib

Overview

Phase: Phase 2
Intervention: Everolimus
Conditions: Differentiated Thyroid Cancer
Sponsor: Thomas Jefferson University
Enrollment: 35
Locations: 1
Primary Endpoint: 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.
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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

The purpose of this research study is to: 1. Find out if sorafenib and everolimus prevent the growth of tumors that have grown when treated with sorafenib alone 2. Find out how long one might benefit from treatment with sorafenib and everolimus 3. Find out what side effects this drug may cause 4. 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.

Registry

clinicaltrials.gov

Start Date

November 2010

End Date

May 2022

Last Updated

4 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Thomas Jefferson University

Responsible Party

Sponsor

Eligibility Criteria

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 \<
•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.

Arms & Interventions

Everolimus and sorafenib

All patients will receive everolimus and sorafenib daily.

Intervention: Everolimus

Everolimus and sorafenib

All patients will receive everolimus and sorafenib daily.

Intervention: Sorafenib

Outcomes

Primary Outcomes

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.

Time Frame: Every 4 weeks

Secondary Outcomes

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 best response in patients receiving everolimus and sorafenib.(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 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)
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)