Study of Everolimus and Sorafenib in Patients With Advanced Thyroid Cancer Who Progressed on Sorafenib Alone
Verified January 2015 by Abramson Cancer Center of the University of Pennsylvania
Information provided by (Responsible Party):
Abramson Cancer Center of the University of Pennsylvania
First received: November 29, 2010
Last updated: January 13, 2015
Last verified: January 2015
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.
Differentiated Thyroid Cancer
||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Phase II Study of Everolimus and Sorafenib in Patients With Metastatic Differentiated Thyroid Cancer Who Have Progressed on Sorafenib Alone
Primary Outcome Measures:
- 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 ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- To evaluate the secondary endpoints of best response in patients receiving everolimus and sorafenib. [ Time Frame: Every 4 weeks ] [ Designated as safety issue: No ]
- 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. [ Time Frame: Every 4 weeks ] [ Designated as safety issue: No ]
- To investigate the effectiveness of mTOR and Raf kinase inhibition in surrogate tissue and tumor samples. [ Time Frame: Every 4 weeks ] [ Designated as safety issue: No ]
- To evaluate the activity of additional signaling pathways in surrogate tissue and tumor samples and explore their relevance to outcome measures. [ Time Frame: Every 4 weeks ] [ Designated as safety issue: No ]
- To evaluate the secondary endpoints of time to disease progression in patients receiving everolimus and sorafenib. [ Time Frame: Every 4 weeks ] [ Designated as safety issue: No ]
- To evaluate the secondary endpoints of duration of response in patients receiving everolimus and sorafenib. [ Time Frame: Every 4 weeks ] [ Designated as safety issue: No ]
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||June 2015 (Final data collection date for primary outcome measure)
Experimental: Everolimus and sorafenib
All patients will receive everolimus and sorafenib daily.
One 5 mg. tablet daily.
Other Name: Afinitor
200 mg. twice daily.
Other Name: Nexavar
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.
|Ages Eligible for Study:
||18 Years to 89 Years
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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.
- 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01263951
|Hospital of the University of Pennsylvania
|Philadelphia, Pennsylvania, United States, 19104 |
|Principal Investigator: Marcia Brose, MD, PhD |
Abramson Cancer Center of the University of Pennsylvania
||Marcia Brose, MD, PhD
||Hospital of the University of Pennsylvania- Abramson Cancer Center
No publications provided
||Abramson Cancer Center of the University of Pennsylvania
History of Changes
|Other Study ID Numbers:
||UPCC 19309, 812004
|Study First Received:
||November 29, 2010
||January 13, 2015
||United States: Food and Drug Administration
Keywords provided by Abramson Cancer Center of the University of Pennsylvania:
Differentiated metastatic thyroid cancer
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on March 02, 2015
Endocrine Gland Neoplasms
Endocrine System Diseases
Head and Neck Neoplasms
Neoplasms by Site
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Protein Kinase Inhibitors