Platinum-based chemotherapy is now regarded a standard first-line treatment for patients with advanced urothelial carcinoma (UC). However, patients who failed to response or experienced progression after platinum-based chemotherapy have a grim prognosis and a standard salvage treatment is not available. UC is known to harbor multiple mutations. In the investigators' own high-throughput molecular profiling study, the most commonly observed mutations included TP53, FGFR3(fibroblast growth factor receptor 3 ) and HRAS. Since RAS signaling can be attenuated using selective farnesyl transferase (FTase) inhibitors, tipifarnib, a highly potent and selective inhibitor of FTase, was proposed to be an effective therapeutic approach in the treatment of UC.
Name: tipifarnibDescription: Tipifarnib will be administered at a starting dose of 900 mg, po, bid on days 1-7 and 15-21 of 28-day treatment cycles. In the absence of unmanageable toxicities, subjects may continue to receive tipifarnib treatment for up to 12 months as long as the Investigator considers that the treatment is providing clinical benefit.Type: Drug
Description: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0(Common Toxicity Criteria for Adverse Effects )Measure: Safety and Tolerability Time: Up to 12 months for each subject
Single Group Assignment
There is one SNP
(missence non-synonymous HRAS mutation and/or STK11: rs2075606 (T>C))HRAS status may have been assessed either in primary tumor tissue, recurrent or metastatic disease. 5. Subject has consented to provide at least 10 unstained tumor slides for retrospective testing of HRAS gene tumor status.