Evaluating the Combination of Everolimus and Sorafenib in the Treatment of Thyroid Cancer

NCT01141309 | Active Not Recruiting Phase 2

• 1 other identifier: 10-060
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 4

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.

Conditions

Thyroid Cancer

Keywords

Everolimus; Sorafenib; Thyroid; 10-060

Outcome Measures

Primary Outcomes (1)

• Determine the response rate of the combination sorafenib and everolimus.

  16 weeks

Secondary Outcomes (3)

• 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

Study Arms (1)

sorafenib with everolimus

EXPERIMENTAL

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

Drug: sorafenib with everolimus

Interventions

sorafenib with everolimus DRUG

Treatment will be with sorafenib 400 mg orally twice a day and everolimus 5 mg orally daily. Restage every 2 cycles \*Cycle = 4 weeks of treatment. Subjects may consent to allowing blood to be drawn for DNA. Two blue top tubes will be required. Approximately 5-6 ml will be needed. This may be done at anytime, including before, during, or after treatment. This is not required to participate in the study.

sorafenib with everolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 3. 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).
• Prior RAI therapy is allowed if \> 3 months prior to initiation of therapy on this protocol and evidence of progression (as defined above) has been documented in the interim. A diagnostic study using \<10 mCi of RAI is not considered RAI therapy.
• Patients may have received prior external beam radiation therapy to index lesions ≥ 4 weeks prior to initiation of therapy on this protocol if there has been documented progression by RECIST criteria. Prior external beam radiation therapy to the non-index lesions is allowed if ≥ 4 weeks prior to initiation of therapy on this protocol.
• ECOG performance status ≤ 2 (or Karnofsky performance status ≥ 60%).
• Patients must have normal organ and marrow function as defined below:
• Absolute neutrophil count ≥1,500/mcL
• Hemoglobin \> 9 gm/dl

You may not qualify if:

• 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.
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 or sorafenib (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
• Patients with clinically significant cardiovascular disease as defined by the following:
• History of CVA within past 6 months
• Myocardial infarction, CABG or unstable angina within past 6 months
• New York Heart Association grade III or greater congestive heart failure or Canadian Cardiovascular Class grade III or greater angina within past 6 months (Appendices A\&B)

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (4)

Memorial Sloan Kettering Cancer Center

Basking Ridge, New Jersey, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Thyroid Neoplasms; Thyroid Diseases

Interventions

Sorafenib; Everolimus

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Sirolimus; Macrolides; Lactones

Study Officials

• Eric Sherman, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2010
• First Posted: June 10, 2010
• Study Start: June 1, 2010
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: July 22, 2025

Record last verified: 2025-07

Locations

US (4)