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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Abramson Cancer Center of the University of Pennsylvania
Sponsor:
Collaborators:
Bayer
Novartis Pharmaceuticals
Information provided by:
Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01263951
First received: November 29, 2010
Last updated: June 26, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Differentiated Thyroid Cancer
Drug: Everolimus
Drug: Sorafenib
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Everolimus and Sorafenib in Patients With Metastatic Differentiated Thyroid Cancer Who Have Progressed on Sorafenib Alone

Resource links provided by NLM:


Further study details as provided by Abramson Cancer Center of the University of Pennsylvania:

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: 40
Study Start Date: November 2010
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus and sorafenib
All patients will receive everolimus and sorafenib daily.
Drug: Everolimus
One 5 mg. tablet daily.
Other Name: Afinitor
Drug: Sorafenib
200 mg. twice daily.
Other Name: Nexavar

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.
  Eligibility

Ages Eligible for Study:   18 Years to 89 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 < 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.
  Contacts and Locations
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

Contacts
Contact: Marcia Brose, MD, PhD 855-216-0098 PennCancerTrials@emergingmed.com

Locations
United States, Pennsylvania
Hospital of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Principal Investigator: Marcia Brose, MD, PhD         
Sponsors and Collaborators
Abramson Cancer Center of the University of Pennsylvania
Bayer
Novartis Pharmaceuticals
Investigators
Principal Investigator: Marcia Brose, MD, PhD Hospital of the University of Pennsylvania- Abramson Cancer Center
  More Information

No publications provided

Responsible Party: Marcia Brose, MD PhD, Hospital of the University of Pennsylvania- Abramson Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01263951     History of Changes
Other Study ID Numbers: UPCC 19309, 812004
Study First Received: November 29, 2010
Last Updated: June 26, 2014
Health Authority: 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:
Thyroid Neoplasms
Thyroid Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Endocrine System Diseases
Everolimus
Sirolimus
Sorafenib
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 21, 2014