Safety and Pharmacology of SNX-5422 Plus Everolimus in Subjects With Neuroendocrine Tumors

Exclusion Criteria

• •Subjects in whom everolimus is contraindicated.
• •Subjects with clinically significant interstitial lung disease, or obstructive disease without sufficient reserve
• •Carcinoid with hormone related symptoms
• •Neuroendocrine cancer of the thyroid or thymus.
• •Rare pancreatic neuroendocrine cancers such as, insulinomas, glucagonomas, gastrinomas.
• •Prior treatment with any Hsp90 inhibitor.
• •Prior failed treatment with mTOR inhibitors
• •CNS metastases that are symptomatic and /or requiring escalating doses of steroids.
• •Major surgery or significant traumatic injury within 4 weeks of starting study treatment.
• •Conventional chemotherapy or radiation within 4 weeks.
• •Palliative radiation within 2 weeks.
• •The need for treatment with medications with clinically-relevant metabolism by the cytochrome P450 (CYP) 3A4 isoenzyme within 3 hours before or after administration of SNX-5422
• •Screening ECG QTc interval ≥470 msec for females, ≥450 msec for males.
• •At increased risk for developing prolonged QT interval, including hypokalemia or hypomagnesemia, unless corrected to within normal limits prior to first dose of SNX-5422; congenital long QT syndrome or a history of torsade de pointes; currently receiving anti-arrhythmics or other medications that may be associated with QT prolongation.
• •Patients with chronic diarrhea or with Grade 2 or greater diarrhea despite appropriate medical management.
• •Gastrointestinal diseases or conditions that could affect drug absorption, including gastric bypass.
• •Gastrointestinal diseases that could alter the assessment of safety, including irritable bowel syndrome, ulcerative colitis, Crohn's disease, or hemorrhagic coloproctitis.
• •History of documented adrenal dysfunction not due to malignancy.
• •Known seropositive for human immunodeficiency virus (HIV) or hepatitis C virus (HCV).
• •History of chronic liver disease.
• •Active hepatitis A or B.
• •Current alcohol dependence or drug abuse.
• •Use of an investigational treatment from 30 days prior to the first dose of SNX-5422 and during the study.
• •Glaucoma, retinitis pigmentosa, macular degeneration, or any retinal changes detected by ophthalmological examination.
• •Other serious concurrent illness or medical condition.
• •Psychological, social, familial, or geographical reasons that would hinder or prevent compliance with the requirements of the protocol or compromise the informed consent process.