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.
Heat shock protein 90 (Hsp90) chaperone proteins stabilize many client proteins including mutant EGFR, and are also hypothesized to help maintain the malignant phenotype of mutant EGFR in lung adenocarcinoma. Treatment of EGFR mutant cell lines with the Hsp90 inhibitor geldanamycin results in cellular degradation, decreased levels of pAKT/cyclin D1, and increased apoptosis. Furthermore, Hsp90 inhibitors hamper growth of tumors in nude mice with gefitinib-resistant H1975-xenografts in vivo. Clinical data showed that mono-therapy with some Hsp90 inhibitors provides stable disease and some patients have partial remissions as best responses in heavily pre-treated non small cell lung cancer patients. SNX-5422 is a pro-drug of SNX-2112, a potent, highly selective, small-molecule inhibitor of the molecular chaperone Hsp90. Inhibitors of the chaperone protein Hsp90 are of current interest because of the central role that Hsp90 plays in the maturation and maintenance of numerous proteins, for example HER2 and mutated EGFR, that are critical for tumor cell viability and growth.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
17
Capsules dosed every other day in the morning starting at a dose of 50 mg/m2. Dose escalation based on safety. Subjects will also receive 150 mg erlotinib daily (in the afternoon).
Georgetown University Medical Center
Washington D.C., District of Columbia, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Number of patients with dose limiting toxicities
Number of patients with dose limiting toxicities defined as adverse events (AE) or laboratory abnormalities of Common Terminology Criteria for Adverse Events(CTCAE) version 4.03 ≥ Grade 3 that are not clearly related to disease progression
Time frame: Day 28 of first dose cycle
Tumor response
Tumor progression relative to baseline; assessment of tumor response will be performed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Time frame: Weeks 4, 12, 20 and 28
Changes in vital signs, physical examination or clinical laboratory from baseline
Descriptive summaries of vital signs, physical examination and quantitative clinical laboratory changes will be presented by treatment received and study visit. Laboratory toxicities will be graded by severity using common terminology criteria for adverse events (CTCAE) Version 4.03. Frequency and percentage of subjects experiencing clinically relevant toxicities will be summarized by treatment received. Summaries may be repeated by treatment cycle.
Time frame: Weeks 4, 8, 12, 16, 20, 24 and 28
Number of patients with ophthalmological changes from baseline
Ophthalmologic assessments (visual acuity, visual field, ophthalmoscopy, dark adaptation, optical coherence tomography) will be presented by cohort, study visit and dose. Number of subjects experiencing clinically relevant changes from baseline in any of these examinations will be presented using descriptive summary
Time frame: Weeks 4, 16 and 28
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