Vorinostat in Treating Patients With Locally Recurrent or Metastatic Cancer of the Urothelium

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00363883
First received: August 10, 2006
Last updated: January 6, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
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
Drug: vorinostat
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Oral Suberoylanilide Hydroxamic Acid (SAHA) in Recurrent or Metastatic Transitional Cell Carcinoma of the Urothelium

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective tumor response rate (CR or PR) according to RECIST criteria [ Time Frame: Up to 26 weeks ] [ Designated as safety issue: No ]
    Exact 95% confidence intervals will be calculated for this estimate (reflecting the interim analysis).


Secondary Outcome Measures:
  • Overall survival [ Time Frame: Up to 26 weeks ] [ Designated as safety issue: No ]
    Will be estimated using the product-limit method of Kaplan and Meier.

  • Time to progression [ Time Frame: From study entry to progression as define by RECIST criteria, assessed up to 26 weeks ] [ Designated as safety issue: No ]
    Will be estimated using the product-limit method of Kaplan and Meier.

  • Toxicity profile assessed using NCI CTCAE 3.0 [ Time Frame: Up to 26 weeks ] [ Designated as safety issue: Yes ]
    Toxicity information recorded will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen. Tables will be constructed to summarize the observed incidence by severity and type of toxicity.


Enrollment: 37
Study Start Date: June 2006
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (vorinostat)
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.
Drug: vorinostat
Given orally
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00363883

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
Sponsors and Collaborators
Investigators
Principal Investigator: David Quinn Beckman Research Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00363883     History of Changes
Other Study ID Numbers: NCI-2012-02844, NCI-2012-02844, PHII-61, 6879, N01CM62209, P30CA033572
Study First Received: August 10, 2006
Last Updated: January 6, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Carcinoma
Carcinoma, Transitional Cell
Kidney Neoplasms
Ureteral Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Diseases
Ureteral Diseases
Vorinostat
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014