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Phase II Study of Oral Suberoylanilide Hydroxamic Acid (SAHA) in Recurrent or Metastatic Transitional Cell Carcinoma of the Urothelium


Phase 2
18 Years
N/A
Not Enrolling
Both
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

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Trial Information

Phase II Study of Oral Suberoylanilide Hydroxamic Acid (SAHA) in Recurrent or Metastatic Transitional Cell Carcinoma of the Urothelium


PRIMARY OBJECTIVES:

I. To determine response rate measured by RECIST criteria for SAHA in patients with
recurrent or metastatic transitional cell carcinoma of the urothelium.

SECONDARY OBJECTIVES:

I. To determine the time to progression and overall survival for SAHA in patients with
recurrent or metastatic transitional cell carcinoma of the urothelium.

II. To provide data on safety and toxicity of SAHA in patients with recurrent or metastatic
transitional cell carcinoma of the urothelium.

III. To obtain preliminary data on molecular correlates in tissue, oral mucosa and blood to
determine feasibility and clinical efficacy.

OUTLINE: This is a multicenter study.

Patients receive oral vorinostat (SAHA) twice daily on days 1-21. Courses repeat every 21
days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood and buccal mucosa collection and tumor biopsies (if accessible) at
baseline and periodically during study for correlative studies. Samples are examined by gene
expression profiling and immunohistochemistry.

After completion of study treatment, patients are followed for up to 26 weeks.

PROJECTED ACCRUAL: A total of 37 patients will be accrued for this study.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective tumor response rate (CR or PR) according to RECIST criteria

Outcome Description:

Exact 95% confidence intervals will be calculated for this estimate (reflecting the interim analysis).

Outcome Time Frame:

Up to 26 weeks

Safety Issue:

No

Principal Investigator

David Quinn

Investigator Role:

Principal Investigator

Investigator Affiliation:

Beckman Research Institute

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02844

NCT ID:

NCT00363883

Start Date:

June 2006

Completion Date:

Related Keywords:

  • 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
  • Urinary Bladder Neoplasms
  • Carcinoma
  • Carcinoma, Transitional Cell
  • Kidney Neoplasms
  • Ureteral Neoplasms

Name

Location

City of HopeDuarte, California  91010