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

• Status: Completed
• Trial end date: 2017-07-01
• Target enrollment: 0
• Participant gender: All

Summary

Heat shock protein 90 (Hsp90) is a chemical in the body that is involve in the promotion of cancer. SNX-5422 is an experimental drug that blocks Hsp90.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Esanex Inc.
• Treatments: Albumin-Bound Paclitaxel; Carboplatin; Paclitaxel

Criteria

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.