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Safety and Pharmacology of SNX-5422 Plus Everolimus in Subjects With Neuroendocrine Tumors
Trial ID: NCT02063958
Study is designed to determine the maximum tolerated dose (MTD) of SNX-5422 when given in combination with everolimus.
A Phase 1, Open-label, Dose-escalation Study of SNX 5422 and Everolimus in Subjects With Neuroendocrine Tumors.
- 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
- 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
- Gastrointestinal diseases or conditions that could affect drug absorption, including
- 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
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