Pasireotide & Everolimus in Adult Patients With Radioiodine-Refractory Differentiated & Medullary Thyroid Cancer

Inclusion Criteria

• Histologic or cytologic confirmation of thyroid cancer (papillary, follicular, medullary); histologic variants such as Hurthle and tall cell variants are allowed.
• Biochemical or radiologic documentation of disease progression within the last 12 months prior to enrollment.
• Presence of at least one site of measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1.
• Patient must have radioiodine refractory disease as defined by one or more of the following conditions:
• All cases of medullary thyroid carcinoma.
• No iodine-uptake on a post- radioactive iodine treatment scan (in presence of low iodine diet and thyroid stimulating hormone (TSH) suppression) in an anatomically defined lesion that qualifies as target lesion by RECIST criteria.

OR

• If there is demonstrable iodine-uptake: the last radioiodine therapy of (≥ 100 mCi) was given within the last 16 months OR if given more than 16 months before enrollment, there is evidence of disease progression after each of the last two radioiodine treatment performed within 16 months of each other (each dose should be ≥ 100mCi).

OR

• If the patient has received the maximum cumulative life time dose of radioactive iodine treatments of at least 600 mCi.
• If the patient declines or is intolerant of radioiodine therapy or if with progressive disease that is, in the opinion of the treating physician, likely to benefit from biologic therapy rather than further iodine therapy e.g. patient with heavy burden of disease
• Age ≥ 18 years.
• Minimum of four weeks since any major surgery or since completion of radiation (patients should have adequately recovered from the acute toxicities of any prior therapy).
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
• Life expectancy of at least 6 months.
• Adequate bone marrow function as shown by: absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L, platelets ≥ 100 x 10⁹/L, Hgb > 9 g/dL.
• Adequate liver function as shown by: serum bilirubin ≤ 1.5 x upper limit of normal (ULN), and serum transaminases activity ≤ 3 x ULN, with the exception of serum transaminases ( 2 weeks at time of randomization.)

Exclusion Criteria

• Prior treatment with not more than 1 systemic agent.
• Patients who have undergone major surgery within 4 weeks prior to study enrollment (tracheotomy, feeding tube or vascular access catheter placement and interventional procedures such as bronchoscopy, upper GI endoscopy or colonoscopy are not considered major surgery).
• Chronic treatment with systemic steroids or another immunosuppressive agent.
• Patients should not receive immunization with attenuated live vaccines during study period or within 1 week of study entry.
• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases.
• Patients with prior or concurrent malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, or other adequately treated in situ cancer, or any other cancer from which the patient has been disease free for five years.
• Patients with uncontrolled diabetes mellitus or a fasting plasma glucose > 1.5 ULN. Note: At the principal investigator's discretion, non-eligible patients can be re-screened after adequate medical therapy has been instituted.
• Patients with symptomatic cholelithiasis (asymptomatic gall stone discovered on screening US should be reviewed by the PI but will not lead to automatic exclusion).
• Liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C):
• History of liver disease, such as cirrhosis or chronic active hepatitis B and C.
• Presence of Hepatitis B surface antigen (HbsAg).
• Presence of Hepatitis C antibody test (anti-HCV).
• Patients who have congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, ventri