Clinical trial NCT01263951: Study of Everolimus and Sorafenib in Patients With Advanced Thyroid Cancer Who Progressed on Sorafenib Alone
Official title: A Phase II Study of Everolimus and Sorafenib in Patients With Metastatic Differentiated Thyroid Cancer Who Have Progressed on Sorafenib Alone
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Differentiated Thyroid Cancer
Keywords: Differentiated metastatic thyroid cancer
Lead sponsor: Thomas Jefferson University
Sponsor class: OTHER
Collaborators: name: Bayer
name: Novartis Pharmaceuticals
First posted: 2010-12-21
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 \< 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.

Primary outcomes:
measure: 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.
timeFrame: Every 4 weeks
Secondary outcomes:
measure: To evaluate the secondary endpoints of best response in patients receiving everolimus and sorafenib.
timeFrame: Every 4 weeks
measure: 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.
timeFrame: Every 4 weeks
measure: To investigate the effectiveness of mTOR and Raf kinase inhibition in surrogate tissue and tumor samples.
timeFrame: Every 4 weeks
measure: To evaluate the activity of additional signaling pathways in surrogate tissue and tumor samples and explore their relevance to outcome measures.
timeFrame: Every 4 weeks
measure: To evaluate the secondary endpoints of time to disease progression in patients receiving everolimus and sorafenib.
timeFrame: Every 4 weeks
measure: To evaluate the secondary endpoints of duration of response in patients receiving everolimus and sorafenib.
timeFrame: Every 4 weeks
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Hospital of the University of Pennsylvania- Abramson Cancer Center
name: Marcia Brose, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: