A Phase II Study to Evaluate the Safety and Efficacy of RAD001 Plus Erlotinib in Patients With Well- to Moderately-Differentiated 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

- ECOG ≤2

- ANC ≥1500/μL

- Plts ≥100,000/μL

- Hgb >9 gm/dL

- Total bilirubin ≤2.0 mg/dL or 1.5XULN

- Serum transaminases ≤2.5xULN (≤5xULN if liver mets)

- Serum Cr ≤2.0 mg/dL or 1.5XULN

- Fasting serum glucose <150 mg/dL or <1.5xULN

- Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides
≤2.5xULN

- 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 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 NYHA Class III or IV

- Unstable angina pectoris, symptomatic CHF, myocardial infarction w/in 6 mths of Day
1, uncontrolled cardiac arrhythmia or any other significant cardiac disease

- Uncontrolled diabetes (fasting serum glucose ≥ 150 mg/dL or >1.5xULN)

- 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 (pts needing
anticoagulation must use LMW heparin)

- 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