Combination of Temsirolimus and Sorafenib in the Treatment of Radioactive Iodine Refractory Thyroid Cancer
Condition: Thyroid Cancer
MeSH terms: Thyroid Neoplasms; Thyroid Diseases
Intervention: Temsirolimus and Sorafenib
Intervention description: Treatment will be with sorafenib 200 mg orally twice a day and temsirolimus 25 mg intravenous weekly. A cycle will be equivalent to 4 weeks of treatment.
Intervention MeSH terms: Sirolimus; Sorafenib; Temsirolimus; MTOR Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 37.0
Sex: All
Minimum age: 21 Years
Healthy volunteers: No
Keywords: thyroid; follicular cell; papillary cell; Hurthle cell; BAY 43-9006; Temsirolimus; Sorafenib; 09-148

Summary:

      The purpose of this study is to find out what effects, good and/or bad, the combination of
      sorafenib and temsirolimus will have on thyroid cancer. Treatment guidelines from the
      National Comprehensive Cancer Network include sorafenib as a treatment option for thyroid
      cancer.

      Temsirolimus is an intravenous medication that is FDA approved for other type of cancers. In
      laboratory studies, the addition of temsirolimus to sorafenib works better than sorafenib
      alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histopathologically confirmed at MSKCC thyroid carcinoma of
             follicular cell origin (D-TC-FCO), which includes papillary, follicular, Hürthle cell
             histology, or anaplastic along with their respective variants.

          -  Available pathology for RAF mutational testing (e.g., paraffin block or 5-10 unstained
             slides). It is not required that mutational testing be completed before starting the
             clinical study.

          -  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
             FDGavid 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). FDGavidity 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) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral 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):

          -  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

          -  Platelets ≥100,000/mcL

          -  Total bilirubin ≤ 1.5 X institutional ULN

          -  AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional ULN

          -  Creatinine ≤ 1.5 X institutional ULN OR

          -  Creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above 1.5
             X institutional ULN [in this circumstance, either of a measured level based on a 24
             hour urine collection, or a calculated level using the Cockcroft and Gault equation:
             (140 - age in years) X (weight in kg) X (0.85 if female)/72 X serum Cr may be used].

          -  International normalized ratio (INR) ≤ 1.5 (or in range INR, usually between 2 and 3,
             if patient is on a stable dose of therapeutic warfarin).

          -  *ULN = upper limit of normal

          -  **unless liver metastasis present in which AST/ALT should be < 5 x ULN.

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Age 21 years old or older.

        Exclusion Criteria:

          -  Patients may not be receiving any other investigational agents.

          -  Patients with known history of active intraparenchymal brain metastasis within
             previous 3 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.

          -  Patients with a reported history of clinically active diverticulosis or diverticulitis
             in the prior 3 years.

          -  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 B&C)
             Clinically significant peripheral vascular disease within past 6 months

          -  Pulmonary embolism, DVT, or other thromboembolic event within past 6 months

          -  Uncontrolled coronary artery disease, angina, congestive heart failure, or ventricular
             arrhythmia requiring acute medical management within past 6 months

          -  History of myocardial infarct, cerebrovascular accident, or transient ischemic event
             within the past 6 month

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  While the use of Angiotensin-Converting Enzyme (ACE) inhibitors is not absolutely
             excluded, efforts should be made to see if patients on ACE inhibitors can be taken off
             the medication or switched to another medication.

          -  Pregnant women will be ineligible; breastfeeding should be discontinued if the mother
             is treated with study drugs.

          -  The use of agents that inhibit or induce CYP3A metabolism is not strictly prohibited,
             but should be avoided if possible. Potential CYP3A inducing agents include
             carbamazepine, phenytoin, barbiturates, rifabutin, rifampicin, and St. John's Wort.
             Potential CYP3A inhibitors include protease inhibitors, antifungals, macrolide
             antibiotics, nefazodone, and selective serotonin inhibitors.