['differentiated thyroid cancer (dtc)', 'poorly differentiated thyroid cancer']
['cabozantinib']

        Inclusion Criteria:

          -  The subject has a histologic or cytologic diagnosis of a DTC tumor (including poorly
             differentiated thyroid cancer but not anaplastic thyroid cancer) that is metastatic or
             unresectable and fulfills the following criteria: a. Subjects must have progressive
             disease as defined by RECIST 1.1 criteria when comparing baseline scans to those
             obtained within the prior 14 months AND b. Subject must have RAIrefractory disease
             based on at least one of the following: i. Prior dose of RAI exceeding 600mCi
             ii.Progression of disease within 18 months following a dose of 100mCi iii. Presence of
             target lesions as defined by modified RECIST criteria which do not take up RAI.

          -  The subject has had an assessment of all known disease sites eg, by computerized
             tomography (CT) scan, magnetic resonance imaging (MRI), bone scan as appropriate,
             within 28 days before the first dose of cabozantinib

          -  The subject is 18 years old on the day of consent.

          -  The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0
             or 1.

          -  The subject has organ and marrow function and laboratory values as follows within 4
             days prior to the first dose of cabozantinib: a. Absolute neutrophil count (ANC)
             1500/mm3without colony stimulating factor support b. Platelets 100,000/mm3 c.
             Hemoglobin 9 g/dL d.Bilirubin 1.5 the upper limit of normal (ULN). For subjects with
             known Gilberts disease, bilirubin 3.0mg/dL e. Serum albumin 2.0 g/dl f. Serum
             creatinine 1.5 ULN or creatinine clearance (CrCl) 50 mL/Page 9 of 16 min. For
             creatinine clearance estimation, the Cockcroft and Gault equation should be used:
             Male: CrCl(mL/min) = (140 - age) × wt (kg) / (serum creatinine × 72) Female: Multiply
             above result by 0.85 g.Alanine aminotransferase (ALT) and aspartate aminotransferase
             (AST) 3.0 ULN h. Lipase 2.0 x the upper limit of normal and no radiologic or clinical
             evidence of pancreatitis i. Urine protein/creatinine ratio (UPCR) 1 j. Serum
             phosphorus, calcium, magnesium and potassium LLN

          -  The subject is capable of understanding and complying with the protocol requirements
             and has signed the informed consent document.

          -  Sexually active subjects (men and women) must agree to use medically accepted barrier
             methods of contraception (eg, male or female condom) during the course of the study
             and for 4 months after the last dose of study drug(s), even if oral contraceptives are
             also used. All subjects of reproductive potential must agree to use both a barrier
             method and a second method of birth control during the course of the study and for 4
             months after the last dose of study drug(s).

          -  Women of childbearing potential must have a negative pregnancy test at screening.
             Women of childbearing potential include women who have experienced menarche and who
             have not undergone successful surgical sterilization (hysterectomy, bilateral tubal
             ligation, or bilateral oophorectomy) or are not postmenopausal. Postmenopause is
             defined as amenorrhea 12 consecutive months. Note: women who have been amenorrheic for
             12 or more months are still considered to be of childbearing potential if the
             amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression
             or any other reversible reason.

          -  An archived tumor specimen is available for collection.

        Exclusion Criteria:

          -  The subject has received cytotoxic chemotherapy (including investigational cytotoxic
             chemotherapy),biologic agents (eg, cytokines or antibodies), or any other anti-cancer
             systemic therapy (including multi-kinase inhibitors).

          -  Prior treatment with cabozantinib

          -  The subject has received radiation therapy: a. to the thoracic cavity, abdomen or
             pelvis within 3 months of the first dose of study treatment thathas with ongoing
             complications or is without complete recovery and healing (CT changes related to
             radiation treatment which are not clinical significant are allowed). b. to bone or
             brain metastasis within 14 days of the first dose of study treatment c. to any other
             site(s) within 28 days of the first dose of study treatment

          -  The subject has received radionuclide treatment within 6 weeks of the first dose of
             study treatment

          -  The subject has received any other type of investigational agent within 28 days before
             the first dose of study treatment.

          -  The subject has not recovered to baseline or CTCAE Grade 1 from toxicity due to all
             prior therapies except alopecia and other non-clinically significant AEs (eg.
             albumin).

          -  The subject has a primary brain tumor.

          -  The subject has active brain metastases or epidural disease who have not been treated
             with radiation therapy (Note: Subjects with brain metastases previously treated with
             whole brain radiation or radiosurgery or subjects with epidural disease previously
             treated with radiation or surgery who are asymptomatic and do not require steroid
             treatment for at least 2 weeks before starting study treatment are eligible.
             Neurosurgical resection of brain metastases or brain biopsy is permitted if completed
             at least 2 months before starting study treatment. (Baseline brain imaging with
             contrast-enhanced CT or MRI scans for subjects with known brain metastases is required
             to confirm eligibility.)

          -  The subject has prothrombin time (PT)/ International Normalized Ratio (INR) or partial
             thromboplastin time (PTT) test 1.3 the laboratory ULN within 7 days before the first
             dose of study treatment.

          -  The subject requires concomitant treatment, in therapeutic doses, with anticoagulants
             such as warfarin or warfarin-related agents, heparin, thrombin or Factor Xa
             inhibitors, or antiplatelet agents (eg, clopidogrel). Low dose aspirin ( 81 mg/day),
             low-dose warfarin (1mg/day), and prophylactic low molecular weight heparin (LMWH) are
             permitted.

          -  The subject requires chronic concomitant treatment of strong CYP3A4 inducers (eg,
             dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin,
             phenobarbital, and St. Johns Wort).

          -  The subject has experienced any of the following: a. clinically-significant
             gastrointestinal bleeding within 6 months before the first dose of study treatment b.
             hemoptysis of 0.5 teaspoon (2.5ml) of red blood within 3 months before the first dose
             of study treatment c. any other signs indicative of pulmonary hemorrhage within 3
             months before the first dose of study treatment

          -  The subject has radiographic evidence of cavitating pulmonary lesion(s)

          -  The subject has tumor in contact with, invading or encasing any major blood vessels

          -  The subject has evidence of tumor invading the GI tract (esophagus, stomach, small or
             large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor
             within 28 days before the first dose of cabozantinib.

          -  The subject has uncontrolled, significant intercurrent or recent illness including,
             but not limited to, the following conditions: a. Cardiovascular disorders including i.
             Congestive heart failure (CHF): New York Heart Association (NYHA) Class III (moderate)
             or Class IV (severe) at the time of screening ii. Concurrent uncontrolled hypertension
             defined as sustained BP 140 mm Hg systolic, or 90 mm Hg diastolic despite optimal
             antihypertensive treatment within 7 days of the first dose of study treatment iii. Any
             history of congenital long QT syndrome iv.

        Any of the following within 6 months before the first dose of study treatment: unstable
        angina pectoris clinically-significant cardiac arrhythmias stroke (including TIA, or other
        ischemic event) myocardial infarction thromboembolic event requiring therapeutic
        anticoagulation (Note: subjects with a venous filter (e.g. vena cava filter) are not
        eligible for this study) b. Gastrointestinal disorders particularly those associated with a
        high risk of perforation or fistula formation including: i. Any of the following within 28
        days before the first dose of study treatment intra-abdominal tumor/metastases invading GI
        mucosa active peptic ulcer disease, inflammatory bowel disease (including ulcerative
        colitis and Crohns disease), diverticulitis, cholecystitis, symptomatic cholangitis or
        appendicitis malabsorption syndrome ii. Any of the following within 6 months before the
        first dose of study treatment: abdominal fistula gastrointestinal perforation bowel
        obstruction or gastric outlet obstruction intra-abdominal abscess.Note: Complete resolution
        of an intra-abdominal abscess must be confirmed prior to initiating treatment with
        cabozantinib even if the abscess occurred more that 6 months before the first dose of study
        treatment. c. Other disorders associated with a high risk of fistula formation including
        PEG tube placement within 3 months before the first dose of study therapy d. Other
        clinically significant disorders such as: i. active infection requiring systemic treatment
        within 28 days before the first dose of study treatment ii. serious non-healing
        wound/ulcer/bone fracture within 28 days before the first dose of study treatment iii.
        history of organ transplant iv. concurrent uncompensated hypothyroidism or thyroid
        dysfunction within 7 days before the first dose of study treatment v. history of major
        surgery as follows: (1) Major surgery within 3 months of the first dose of cabozantinib if
        there were no wound healing complications or within 6 months of the first dose of
        cabozantinib if there were wound complications (2) Minor surgery within 1 months of the
        first dose of cabozantinib if there were no wound healing complications or within 3 months
        of the first dose of cabozantinib if there were wound complications In addition complete
        wound healing from prior surgery must be confirmed at least 28 days before the first dose
        of cabozantinib irrespective of the time from surgery

          -  The subject is unable to swallow tablets

          -  The subject has a corrected QT interval calculated by the Fridericia formula (QTcF)
             500 ms within 28 days before randomization. . Note: if initial QTcF is found to be 500
             ms, two additional EKGs separated by at least 3 minutes should be performed. If the
             average of these three consecutive results for QTcF is 500 ms, the subject meets
             eligibility in this regard

          -  The subject is pregnant or breastfeeding.

          -  The subject has a previously identified allergy or hypersensitivity to components of
             the study treatment formulation. 21. The subject is unable or unwilling to abide by
             the study protocol or cooperate fully with the investigator or designee.
      