Safety and Pharmacology of SNX-5422 Plus Carboplatin and Paclitaxel in Subjects With Solid Tumors

Inclusion Criteria:

• Males or non-pregnant, non-breastfeeding females 18 years-of-age or older.
• Pathologic evidence of Small Cell Lung Cancer, or Non-Small Cell Lung Cancer.
• No more than one prior line of antitumor therapy for metastatic disease, excluding prior treatment with tyrosine kinase inhibitors. An interval of at least 1 week is required for washout of the tyrosine kinase inhibitor.
• Measurable disease using RECIST criteria (version 1.1).
• Life expectancy of at least 3 months.
• 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 (ALT) or aspartate aminotransferase (AST) ≤2.0 x ULN except in subjects with known hepatic metastasis, where AST or ALT can be ≤5.0 x ULN.
  • Hemoglobin ≥9 mg/dL.
  • Estimated creatinine clearance of ≥40 mL/min
• Recovered from toxicities of previous anticancer therapy to CTCAE Grade ≤ 1 with the exception of alopecia.
• Signed informed consent form (ICF)
• Subjects with reproductive capability must agree to practice adequate contraception methods.
• Adequate venous access

Exclusion Criteria:

• CNS metastases that are symptomatic and /or requiring steroids.
• Prior treatment with any Hsp90 inhibitor.
• Major surgery or significant traumatic injury within 4 weeks of starting study treatment.
• 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 maximal 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.
• Treatment with other anticancer drugs within 28 days or 5 half-lives of anticancer therapy (whichever is shorter), and treatment with any other investigational agent is prohibited from 30 days prior to the first dose of SNX-5422 and throughout the study.
• Radiation treatment within 2 weeks.
• 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.