Cabozantinib In Advanced Radioactive-Iodine Refractory Differentiated Thyroid Cancer.

Exclusion Criteria

• •1. Prior treatment with any of the following:
• •1. Cabozantinib.
• •2. Selective small-molecule BRAF kinase inhibitor (eg, vemurafenib, dabrafenib).
• •3. Immune checkpoint inhibitor therapy (eg, PD-1 or PD-L1 targeting agent).
• •4. Systemic chemotherapy regimen (given as a single agent or in combination with another chemotherapy agent).
• •2. Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks or 5 half-lives of the agent, whichever is longer, before first dose of study treatment.
• •3. Receipt of any type of anticancer antibody (including investigational antibody) within 4 weeks before first dose of study treatment.
• •5. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of inclusion.
• •6. Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel), except for the following allowed anticoagulants:
• •1. Low-dose aspirin for cardioprotection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
• •2. Anticoagulation with therapeutic doses of LMWH in subjects without known brain metastases who are on a stable dose of LMWH for at least 6 weeks before first dose of study treatment and who have had no clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
• •7. The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• •a. Cardiovascular disorders: i. Congestive heart failure class 3 or 4 as defined by the New York Heart Association, unstable angina pectoris, serious cardiac arrhythmias.
• •ii. Uncontrolled hypertension defined as sustained BP \> 150 mm Hg systolic or \> 100 mm Hg diastolic despite optimal antihypertensive treatment.
• •iii. Stroke (including transient ischemic attack \[TIA\]), myocardial infarction, or other ischemic event, or thromboembolic event (eg, deep venous thrombosis \[DVT\], pulmonary embolism) within 6 months before first dose of study treatment. Note: Patients with a more recent diagnosis of DVT are allowed if stable, asymptomatic, and treated with LMWH for at least 6 weeks before first dose of study treatment.
• •b. Gastrointestinal disorders (eg, malabsorption syndrome or gastric outlet obstruction) including those associated with a high risk of perforation or fistula formulation: i. Tumors invading the GI tract, active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic or biliary duct, or gastric outlet obstruction.
• •ii. Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment. Note: Complete healing of an intra-abdominal abscess must be confirmed prior to the first dose of study treatment.
• •c. Clinically significant hematemesis or hemoptysis of \> 0.5 teaspoon (\> 2.5 mL) of red blood or history of other significant bleeding within 3 months before the first dose of study treatment.
• •d. Cavitating pulmonary lesion(s) or known endobronchial disease manifestation. e. Lesions invading major pulmonary blood vessels. f. Other clinically significant disorders such as: i. Active infection requiring systemic treatment, infection with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome-related illness, or chronic hepatitis B (HBV) or C (HCV) infection.
• •ii. Serious non-healing wound/ulcer/bone fracture. iii. Malabsorption syndrome. iv. Moderate to severe hepatic impairment (Child-Pugh B or C). v. Requirement for hemodialysis or peritoneal dialysis. vi. Uncontrolled diabetes mellitus. vii. History of solid organ transplantation.
• •9. Corrected QT interval calculated by the Fridericia formula (QTcF) \> 500 ms within 28 days before the first dose of study treatment.
• •Note: If a single ECG shows a QTcF with an absolute value \> 500 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these 3 consecutive results for QTcF will be used to determine eligibility.
• •10. Patients who are not able to swallow tablets.
• •11. Previously identified allergy or hypersensitivity to components of the study treatment formulations.
• •12. Diagnosis of another malignancy within 3 years before the first dose of study treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy.
• •13. Women pregnant or breastfeeding. Fertile and sexually active patients who are not willing to use the appropriate highly effective contraceptive methods.
• •14. Any underlying medical or psychiatric disorder, which, in the opinion of the investigator, makes the administration of cabozantinib unsafe or interferes with the informed consent process or trial procedures.