RAD001 and Erlotinib in Patients With Neuroendocrine Tumors
Condition: Neuroendocrine Tumors
MeSH terms: Neuroendocrine Tumors
Intervention: RAD001; erlotinib
Intervention description: 5 mg/day PO (oral); 100 mg/day (oral)
Intervention MeSH terms: Everolimus; Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: neuroendocrine; islet cell; carcinoid; pancreatic neuroendocrine; paraganglioma; pheochromocytoma; RAD001; everolimus; erlotinib; Tarceva

Summary:

      The purpose of this study is to test how safe and effective the combination of RAD001 and
      erlotinib is in patients with neuroendocrine tumors.
    

Eligibility criteria:

        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