RAD001 and Erlotinib in Patients With Neuroendocrine Tumors

Inclusion Criteria:

* \>=1 measurable disease site per RECIST, not previously irradiated (if previous radiation to marker lesion(s), need evidence of PD)
* Histologic dx of well- to moderately-differentiated NET: low- or intermediate-grade, islet cell carcinoma, pancreatic NET, carcinoid, atypical carcinoid, paraganglioma, pheochromocytoma. No longer enrolling carcinoid patients as of 4/25/2011.
* ≥4 wks since completion of prior investigational drug tx or other tx(radiation, chemotherapy, immunotherapy, antibody-based tx); recovery from acute toxicities of prior tx
* Eastern Cooperative Oncology Group (ECOG) ≤2
* Absolute Neutrophil Count (ANC) ≥1500/μL
* Plts ≥100,000/μL
* Hgb \>9 gm/dL
* Total bilirubin ≤2.0 mg/dL or 1.5X upper limit of normal (ULN)
* Serum transaminases ≤2.5x ULN (≤5xULN if liver mets)
* Serum Cr ≤2.0 mg/dL or 1.5X ULN
* Fasting serum glucose \<150 mg/dL or \<1.5x ULN
* Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤2.5xULN
* International Normalized Ratio (INR) ≤1.5
* Written informed consent, compliance w/study requirements
* Archived tissue if available
* Negative urine/serum pregnancy test w/in 7 days prior to Day 1

Exclusion Criteria:

* Poorly differentiated NET, high-grade NET, adenocarcinoid, goblet cell carcinoid, small cell carcinoma
* Major surgery or traumatic injury w/in 4 wks, inadequate recovery from side effects of any surgery, or likely to require major surgery during study
* Liver-directed therapy w/in 2 mths of enrollment. Prior tx w/ radiotherapy (including radiolabeled spheres, cyberknife, hepatic arterial embolization (w/ or w/o chemotherapy), cryotherapy/ablation) allowed if areas of measurable disease being used for the study are not affected, or if PD can clearly be documented in the area
* Prior tx w/ EGFR inhibitor or mTOR inhibitor
* Known hypersensitivity to RAD001 or other rapamycins
* Chronic, systemic tx w/ corticosteroids or another immunosuppressive agent (topical or inhaled corticosteroids are allowed)
* Immunization w/ attenuated live vaccines w/in 1 wk of study entry or during study
* Uncontrolled brain or leptomeningeal mets, including pts who continue to require glucocorticoids for brain or leptomeningeal mets
* Other malignancies w/in the past 3 years except for adequately treated carcinoma of the cervix, basal/squamous cell skin carcinomas, or other in situ cancer
* Severe and/or uncontrolled intercurrent medical conditions or other conditions that may affect study participation, including, but not limited to:
* Severely impaired lung function (spirometry and Diffusing capacity of the lungs for carbon monoxide (DLCO) that is 50% of the normal predicted value and/or O2 saturation ≤88% at rest on room air)
* Symptomatic congestive heart failure (CHF) of New York Heart Association (NYHA) Class III or IV
* Unstable angina pectoris, symptomatic CHF, myocardial infarction w/in 6 months of Day 1, uncontrolled cardiac arrhythmia or any other significant cardiac disease
* Uncontrolled diabetes (fasting serum glucose ≥ 150 mg/dL or \>1.5x upper limit of normal (ULN))
* Any active (acute or chronic) or severe infection, disorder, or nonmalignant medical illness that is uncontrolled or whose control may be jeopardized by study tx
* Liver disease
* Hx of HIV seropositivity or other immunocompromised state
* GI function impairment or disease that may alter absorption of RAD001 or erlotinib
* Active, bleeding diathesis or on oral anti-vitamin K medication (patients needing anticoagulation must use low molecular weight heparin (LMWH))
* Hx of other disease, metabolic dysfunction, or physical exam or lab finding giving reasonable suspicion of disease/condition that contraindicates study tx, might affect study results or puts the pt at high risk
* Pregnant or breast feeding females
* Adults of reproductive potential not willing to use effective methods of birth control during tx and ≥8 wks after completing tx
* Inability to comply w/ objectives and procedures
* Inability to comply w/ concomitant medication restrictions