RAD001 and Erlotinib in Patients With Neuroendocrine Tumors

• Status: Terminated
• Trial end date: 2016-08-20
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, San Francisco
• Collaborators: Genentech, Inc.; Novartis Pharmaceuticals; The V Foundation for Cancer Research
• Treatments: Erlotinib Hydrochloride; Everolimus; Sirolimus

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