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

Inclusion Criteria:

   - Males or non-pregnant, non-breastfeeding females 18 years-of-age or older.

   - Archived neuroendocrine tumor sample or biopsy sample (will also be used for genetic
   testing).

   - Pathologic evidence of chemo-resistant Small Cell Lung cancer (relapse <90 days after
   1st line), chemo-sensitive Small Cell Lung Cancer (relapse >90 days after first line),
   locally advanced metastatic neuroendocrine tumor of gastro-entero, pancreatic,
   pulmonary (other than Small Cell Lung) or thymic origin, or advanced renal cell
   carcinoma for which everolimus is indicated.

   - Measurable (RECIST) indicator lesion not previously irradiated.

   - Life expectancy of at least 3 months.

   - No more than 4 prior lines of systemic anti-cancer therapy.

   - Karnofsky performance score ≥70.

   - Adequate baseline laboratory assessments, including

      - Absolute neutrophil count (ANC) ≥1.5 x 109/L.

      - WBC >3000/microliter

      - Platelet count of ≥100 x 109/L.

      - Total bilirubin level ≤1.5 times institutional upper limit of normal (ULN),
      alanine aminotransferase or aspartate aminotransferase ≤2 x ULN

      - Hemoglobin ≥9 mg/dL.

      - Creatinine <1.5 X upper limit of normal or estimated plasma creatinine clearance
      of ≥40 mL/min

   - Signed informed consent form

   - Recovered from toxicities of previous anticancer therapy

   - Subjects with reproductive capability must agree to practice adequate contraception
   methods.

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.