Safety and Efficacy of SNX-5422 in Human Epidermal Growth Factor Receptor 2 (HER2) Positive Cancers

Exclusion Criteria

• •Subjects with symptomatic central nervous system (CNS) metastases who are neurologically unstable
• •Prior treatment with any Hsp90 inhibitor.
• •Surgery, radiotherapy, or lesion ablative procedure to the only area of measurable disease.
• •Major surgery within 4 weeks prior to first dose of SNX-5422.
• •Treatment with chronic immunosuppressants (e.g., cyclosporine following transplantation).
• •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
• •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
• •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.