Vorinostat in Treating Patients With Locally Recurrent or Metastatic Cancer of the Urothelium
Condition: Localized Transitional Cell Cancer of the Renal Pelvis and Ureter; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Transitional Cell Carcinoma of the Bladder
MeSH terms: Carcinoma; Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Kidney Neoplasms; Ureteral Neoplasms; Recurrence
Intervention: vorinostat; laboratory biomarker analysis
Intervention description: Given orally; Correlative studies
Intervention MeSH terms: Vorinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell
      growth. This phase II trial is studying how well vorinostat works in treating patients with
      locally recurrent or metastatic cancer of the urothelium.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a pathological diagnosis of transitional cell carcinoma of the
             bladder or urothelium with less than 25% component of other cell types such as small
             cell, neuroendocrine or squamous cell carcinoma; archival tumor tissue must be
             available for classification and correlates as described in this protocol or otherwise
             the patient must be willing to undergo biopsy prior to trial entry

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded) as >=
             20 mm with conventional techniques or as >= 10 mm with spiral CT scan; patients with
             boney metastases are allowed to participate in the study provided they also have
             non-osseous disease that is measurable

          -  Patients must have recurred or progressed on or subsequent to platinum-based
             chemotherapy in the adjuvant or advanced setting; patients treated with a second line
             of chemotherapy may be included provided more than six months elapsed from the
             completion of the first line of chemotherapy to the start of the second; patients may
             have had any number of prior intravesical therapies for superficial bladder cancer;
             patients may also have had one experimental biologic therapy for their metastatic
             urothelial cancer provided this was not an agent known to act through histone
             deacetylation or demethylation; these compounds include sodium butyrate, trichostatin
             A (TSA), trapoxin (TPX), MS-27-275 and depsipeptide

          -  Life expectancy of greater than 3 months

          -  ECOG performance status =< 2 (Karnofsky >= 60%)

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Total bilirubin within normal institutional limits

          -  AST (SGOT)/ALT (SGPT) =< 2.5 x institutional upper limit of normal unless there are
             liver metastases in which case AST/ALT must be =< 5 x the upper limits of
             institutional normal

          -  Creatinine =< 1.5 times normal institutional limits OR creatinine clearance >= 40
             mL/min/1.73 m^2 for patients with creatinine levels above 1.5 times institutional
             normal

          -  Eligibility of patients receiving any medications or substances known to effect or
             with the potential to effect the activity or pharmacokinetics of SAHA will be
             determined following review by the principal investigator

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for
             the duration of study participation; should a woman become pregnant or suspect she is
             pregnant while participating in this study, she should inform her treating physician
             immediately

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or those who have not
             recovered from adverse events due to agents administered more than 4 weeks earlier

          -  Patients may not be receiving any other investigational agents

          -  Patients with known brain metastases should be excluded from this clinical trial
             because of their poor prognosis and because they often develop progressive neurologic
             dysfunction that would confound the evaluation of neurologic and other adverse events

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to SAHA; these compounds include sodium butyrate, trichostatin A (TSA),
             trapoxin (TPX), MS-27-275 and depsipeptide

          -  Prior treatment with more than 2 cytotoxic chemotherapy regimens for urothelial
             transitional cell cancer

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Pregnant women are excluded from this stud; breastfeeding should be discontinued if
             the mother is treated with SAHA

          -  HIV-positive patients receiving combination antiretroviral therapy are ineligible

          -  Patients should not have taken valproic acid for at least two weeks prior to study
             entry