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

Not Recruiting

Trial ID: NCT02063958


Study is designed to determine the maximum tolerated dose (MTD) of SNX-5422 when given in combination with everolimus.

Official Title

A Phase 1, Open-label, Dose-escalation Study of SNX 5422 and Everolimus in Subjects With Neuroendocrine Tumors.

Stanford Investigator(s)

Alice C. Fan
Alice C. Fan

Assistant Professor of Medicine (Oncology) and, by courtesy, of Urology

George A. Fisher Jr.
George A. Fisher Jr.

Colleen Haas Chair in the School of Medicine


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

   - 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

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,

   - 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

   - 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

   - 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

   - 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

   - 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


drug: SNX-5422

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Cancer Clinical Trials Office

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