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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Differentiated Thyroid Cancer
• Intervention / Treatment: Drug: Everolimus; Drug: Sorafenib

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.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Everolimus and sorafenib; All patients will receive everolimus and sorafenib daily.	Drug: Everolimus; One 5 mg. tablet daily.; Other Names: Afinitor; Drug: Sorafenib; 200 mg. twice daily.; Other Names: Nexavar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Thomas Jefferson University
• Collaborators: Bayer; Novartis Pharmaceuticals
• Investigators: Principal Investigator: Marcia Brose, MD, PhD, Hospital of the University of Pennsylvania- Abramson Cancer Center

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): February 1, 2021
• Study Completion (Anticipated): May 1, 2022

Study Registration Dates

• First Submitted: November 29, 2010
• First Submitted That Met QC Criteria: December 17, 2010
• First Posted (Estimate): December 21, 2010

Study Record Updates

• Last Update Posted (Actual): October 26, 2021
• Last Update Submitted That Met QC Criteria: October 18, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Differentiated metastatic thyroid cancer
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Thyroid Diseases; Thyroid Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protein Kinase Inhibitors; Sorafenib; Everolimus
• Other Study ID Numbers: UPCC 19309; 812004 (Other Identifier: University of Pennsylvania IRB #1)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Not at this time