Phase II Study Evaluating the Combination of Everolimus and Sorafenib in the Treatment of Thyroid Cancer

Memorial Sloan Kettering Cancer Center3 sites in 1 country41 target enrollmentJune 1, 2010

ConditionsThyroid Cancer

Interventionssorafenib with everolimus

Drugssorafenib with everolimus

Overview

Phase: Phase 2
Intervention: sorafenib with everolimus
Conditions: Thyroid Cancer
Sponsor: Memorial Sloan Kettering Cancer Center
Enrollment: 41
Locations: 3
Primary Endpoint: Determine the response rate of the combination sorafenib and everolimus.
Status: Active, not recruiting
Last Updated: 9 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to find out what effects, good and/or bad, the combination of sorafenib and everolimus will have on your thyroid cancer. Treatment guidelines from the National Comprehensive Cancer Network include sorafenib as a treatment option for thyroid cancer. Sorafenib is pill that is approved by the FDA for the treatment of kidney and liver cancers. Sorafenib may work in many different ways. It helps decrease the blood supply to tumors. By doing so, it may limit the tumor's source of oxygen and nutrients and prevent the tumor from growing. Everolimus is an oral medication that is FDA approved for the treatment of kidney cancer. It inhibits a protein kinase called mTOR ("mammalian Target of Rapamycin"). In laboratory studies, the addition of everolimus to sorafenib works better than sorafenib alone. These two drugs are being used together to treat other types of cancer in other clinical studies. In addition, the cancer will be evaluated to help us find factors that can help predict who would benefit most from this combination of drugs.

Registry

clinicaltrials.gov

Start Date

June 1, 2010

End Date

June 1, 2026

Last Updated

9 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Memorial Sloan Kettering Cancer Center

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patients must have histopathologically confirmed at MSKCC thyroid carcinoma.
•Patient must agree to allow 2 biopsies of any malignant lesion that can be accessed by ultrasound (e.g., cervical lymph node, peripheral nodule) or without the aid of radiology (i.e., skin lesion)
•Patients must have surgically inoperable and/or recurrent/metastatic disease.
•Patients must have a PET scan prior to the protocol start date and have at least one FDG-avid lesion that has not been removed surgically or radiated (unless it has progressed by RECIST criteria after the completion of radiation therapy and is still FDG-avid). FDG-avidity will be defined as any focus of increased FDG uptake greater than normal activity with SUV maximum levels greater than or equal to
•PET scan can have been done at any time prior to the start of therapy, although it is recommended that it be done within 3 months prior to the start of therapy.
•Patients must have measurable disease by RECIST criteria, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan. For malignant lymph nodes, the short axis must be \> 15 mm when assessed by CT scan; performed ≤ 4 weeks of protocol start date.
•Patients must have progressive disease defined by at least one of the following occurring during or after previous treatment (including RAI treatment) unless newly diagnosed:
•The presence of new or progressive lesions on CT/MRI.
•New lesions on bone scan or PET scan.
•Rising thyroglobulin level (documented by a minimum of three consecutive rises, with an interval of \> 1 week between each determination).

Exclusion Criteria

•Anaplastic thyroid carcinoma present in any biopsy or fine needle aspirate specimen over the previous year, unless a pathologist at MSKCC disagrees with this diagnosis.
•Previous treatment with a known mTOR inhibitor (e.g., everolimus, temsirolimus) or sorafenib for thyroid cancer.
•Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.)
•Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study
•Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
•Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period
•Patients may not be receiving any other investigational agents.
•Patients with known history of active intraparenchymal brain metastasis within previous 3 months. Previously treated lesions are eligible if they either have been surgically removed and there are no indications of metastatic disease on imaging of the brain or if there has been no progression after treatment for at least 6 months.
•Serious or non-healing wound, ulcer, or bone fracture.
•History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment.

Arms & Interventions

sorafenib with everolimus

This is a two-stage phase II study combining sorafenib with everolimus in patients with thyroid cancer.

Intervention: sorafenib with everolimus

Outcomes

Primary Outcomes

Determine the response rate of the combination sorafenib and everolimus.

Time Frame: 16 weeks

Secondary Outcomes

Evaluate if mutations in the pTEN, PI3K AKT, mTOR pathway, predict response to therapy.(done prior to the start of therapy and again 3-5 weeks after the start of treatment)
Determine the progression free survival under the combination of sorafenib and everolimus.(2 years)
Assess safety and toxicity.(once a week)