Safety and Pharmacology Study of SNX-5422 in Subjects With Resistant Lung Adenocarcinoma

• Status: Completed
• Trial end date: 2016-08-01
• Target enrollment: 0
• Participant gender: All

Summary

Heat shock protein 90 (Hsp90) is a chemical in the body that is involved 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: Erlotinib Hydrochloride

Criteria

Inclusion Criteria:

• Males or non-pregnant, non-breastfeeding females 18 years-of-age or older.

• Received treatment with erlotinib/gefitinib throughout the one month prior to enrollment and at least six months at any time.

• Must have undergone a biopsy after the development of acquired resistance.

• Pathologic evidence of advanced lung adenocarcinoma (stage IIIB or stage IV) confirmed histologically/cytologically

• Radiographic progression by RECIST during treatment with erlotinib/gefitinib.

• Measurable (RECIST) indicator lesion not previously irradiated.

• No more than 4 prior lines of cytotoxic chemotherapy, including erlotinib/gefitinib

• 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) ≤1.5 x ULN.

• Hemoglobin ≥9 mg/dL.

• Creatinine <1.5 X upper limit of normal or estimated plasma creatinine clearance of ≥40 mL/min (using the Cockroft-Gault equation)

• Signed informed consent form (ICF).

• Subjects with reproductive capability must agree to practice adequate contraception methods.

• Adequate venous access.

Exclusion Criteria:

• CNS metastases which are symptomatic and /or requiring escalating doses of steroids.

• Prior treatment with any Hsp90 inhibitor.

• Conventional chemotherapy, radiation or monoclonal antibodies within 4 weeks (erlotinib/gefitinib therapy within the past 4 weeks IS allowed).

• 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 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.

• 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 process.