['urothelial carcinoma']
['tipifarnib']

        Inclusion Criteria:

          1. Subject is at least 20 years of age.

          2. Subject has a histologically or cytologically confirmed diagnosis of urothelial
             carcinoma arising from urinary bladder or upper urinary tract.

          3. Subject has been treated with platinum-based chemotherapy for advanced disease. They
             must have refractory or progressive disease for which there is no further curative
             therapy available.

          4. Subject has been treated with platinum-based chemotherapy for advanced disease. They
             must have refractory or progressive disease for which there is no further curative
             therapy available.

             Subject has a tumor that carries a missense HRAS mutation according to a standard
             methodology using Illumina HiSeqTM. (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.

          6. Must have a life expectancy of 3 months or more

          7. Subject has measurable disease according to RECIST(Response Evaluation Criteria in
             Solid Tumors ) v1.1 and has relapsed (progressive disease) or is refractory to prior
             therapy.

          8. At least 2 weeks since the last systemic therapy regimen prior to enrolment. Subjects
             must have recovered to NCI CTCAE v. 4.03 < Grade 2 from all acute toxicities
             (excluding Grade 2 toxicities that are not considered a safety risk by the Sponsor and
             Investigator) or toxicity must be deemed irreversible by the Investigator.

          9. At least 2 weeks since last radiotherapy if radiation was localized to the only site
             of measurable disease, unless there is documentation of disease progression of the
             irradiated site. Patients must have recovered from all acute toxicities from
             radiotherapy.

         10. ECOG(Eastern Cooperative Oncology Group ) performance status of 0 or 1.

         11. Acceptable liver function:

               1. Bilirubin ≤ 1.5 times upper limit of normal (x ULN); does not apply to subjects
                  with Gilbert's syndrome diagnosed as per institutional guidelines.

               2. AST (SGOT,aspartate aminotransferase ) and ALT (SGPT,Alanine aminotransferase) ≤
                  3 x ULN; if liver metastases are present, then ≤ 5 x ULN is allowed.

         12. Acceptable renal function with serum creatinine ≤ 1.5 x ULN or a calculated creatinine
             clearance ≥ 60 mL/min using the Cockcroft-Gault or MDRD(Modification of Diet in Renal
             Disease ) formulas. Serum potassium with normal or ≤ CTCAE Grade 1 with or without
             supplementation.

         13. Acceptable hematologic status (without growth factor support or transfusion
             dependency):

               1. ANC(absolute neutrophil count )>1500 cells/μL.

               2. Platelet count >100,000/μL.

               3. Hemoglobin >9.0 g/dL.

         14. Female subjects must be either:

               1. Of non-child-bearing potential (surgically sterilized or at least 2 years
                  post-menopausal); or

               2. If of child-bearing potential, subject must use an adequate method of
                  contraception consisting of two-barrier method or one barrier method with a
                  spermicide or intrauterine device. Both females and male subjects with female
                  partners of child-bearing potential must agree to use an adequate method of
                  contraception for 2 weeks prior to screening, during, and at least 4 weeks after
                  last dose of trial medication. Female subjects must have a negative serum or
                  urine pregnancy test within 72 hours prior to start of trial medication.

               3. Not breast feeding at any time during the study.

         15. Written and voluntary informed consent understood, signed and dated.

        Exclusion Criteria:

          1. Ongoing treatment with an anticancer agent not contemplated in this protocol.

          2. Prior treatment (at least 1 full treatment cycle) with an FTase inhibitor.

          3. Any history of clinically relevant coronary artery disease or myocardial infarction
             within the last 3 years, New York Heart Association (NYHA) grade III or greater
             congestive heart failure, cerebrovascular attack within the prior year, or current
             serious cardiac arrhythmia requiring medication except atrial fibrillation.

          4. Known uncontrolled brain, leptomeningeal or epidural metastases (unless treated and
             well controlled for at least 4 weeks prior to Cycle 1 Day 1). Subjects that develop
             brain metastasis during the study may have their treatment interrupted to receive a
             course of cranial radiation and restart trial medication after a recovery period of at
             least 1 week. High dose corticosteroids may be employed for the management of cranial
             radiation but must be tapered off before resuming treatment.

          5. Non-tolerable > Grade 2 neuropathy or evidence of unstable neurological symptoms
             within 4 weeks of Cycle 1 Day 1.

          6. Major surgery, other than diagnostic surgery, within 4 weeks prior to Cycle 1 Day 1,
             without complete recovery.

          7. Double primary cancer of other site(s), except for cured ones at the discretion of
             investigator

          8. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
             therapy. Known infection with HIV, or an active infection with hepatitis B or
             hepatitis C.

          9. Subjects who have exhibited allergic reactions to tipifarnib, structural compounds
             similar to tipifarnib or to its excipients.

         10. Concomitant disease or condition that could interfere with the conduct of the study,
             or that would, in the opinion of the Investigator, pose an unacceptable risk to the
             subject in this study.

         11. The subject has legal incapacity or limited legal capacity.

         12. Dementia or significantly altered mental status that would limit the understanding or
             rendering of informed consent and compliance with the requirements of this protocol.
             Unwillingness or inability to comply with the study protocol for any reason.

         13. QTcF interval ≥ 470 msecs
      