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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.
Full description
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.
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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
Signed informed consent form (ICF).
Subjects with reproductive capability must agree to practice adequate contraception methods.
Adequate venous access.
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17 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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