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

Exclusion Criteria

• •1. Prior treatment with not more than 1 systemic agent.
• •2. 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).
• •3. Chronic treatment with systemic steroids or another immunosuppressive agent.
• •4. Patients should not receive immunization with attenuated live vaccines during study period or within 1 week of study entry.
• •5. Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases.
• •6. 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.
• •7. 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.
• •8. Patients with symptomatic cholelithiasis (asymptomatic gall stone discovered on screening US should be reviewed by the PI but will not lead to automatic exclusion).
• •9. 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).
• •10. Patients who have congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block or a history of acute myocardial infarction within the six months preceding enrollment.
• •* QT corrected Fridericia's method (QTcF) at screening \> 470 msec.
• •* History of syncope or family history of idiopathic sudden death.
• •* Sustained or clinically significant cardiac arrhythmias.
• •* Risk factors for Torsades de Pointes such as hypokalemia, hypomagnesemia, cardiac failure, clinically significant/symptomatic bradycardia, or high-grade atrioventricular (AV) block.
• •* Concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes, or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism or cardiac failure.
• •* Concomitant medication(s) known to increase the QT interval.
• •12. Patients with the presence of active or suspected acute or chronic uncontrolled infection or with a history of immunocompromise, including a positive HIV test result (ELISA and Western blot).
• •13. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• •* Severely impaired lung function (as defined as spirometry and diffusing capacity of lung for carbon monoxide \[DLCO\] that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air).
• •* Any active (acute or chronic) or uncontrolled infection/disorders.
• •* Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy.
• •* Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (everolimus).
• •* Patients who have a history of alcohol or drug abuse in the 6 month period prior to receiving treatment with pasireotide or RAD001.
• •* History of, or current alcohol misuse/abuse within the past 12 months.
• •* Acute or chronic pancreatitis.
• •14. Women who are pregnant or breast feeding, or women/men of reproductive potential who are not using and unwilling to practice an effective method of birth control. (Women of childbearing potential \[WOCBP\] must have a negative serum pregnancy test within 7 days prior to administration of pasireotide and RAD001.)
• •15. Male patient whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment.
• •16. Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients.
• •17. Known hypersensitivity to somatostatin analogues or any component of the pasireotide or octreotide LAR formulations.
• •18. History of noncompliance to medical regimens.
• •19. Patients unwilling to or unable to comply with the protocol.
• •20. Patients taking medications known to be strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitors.