Localized Transitional Cell Cancer of the Renal Pelvis and UreterPhase 2NCT00363883
Vorinostat in Treating Patients With Locally Recurrent or Metastatic Cancer of the Urothelium
A Phase 2 study testing vorinostat and laboratory biomarker analysis in people with Localized Transitional Cell Cancer of the Renal Pelvis and Ureter and Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- 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
- What is being tested?
- vorinostat and laboratory biomarker analysis
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2006to Dec 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Southern California, Norris
Los Angeles, California, 90033
About this study
Official title: Phase II Study of Oral Suberoylanilide Hydroxamic Acid (SAHA) in Recurrent or Metastatic Transitional Cell Carcinoma of the Urothelium
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine response rate measured by RECIST criteria for SAHA in patients with recurrent or metastatic transitional cell carcinoma of the urothelium.
SECONDARY OBJECTIVES:
- 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.
- Conditions
- 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
- Being tested
- vorinostat, laboratory biomarker analysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
vorinostatDrug
Also called L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza
Given orally
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (vorinostat) | Experimental | 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. Receives: Drug: vorinostat; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Tumor Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Measured: Response assessed after every 2 cycles (6 weeks) up to 26 weeks
Secondary outcomes (2)
Overall Survival
Will be estimated using the product-limit method of Kaplan and Meier.
Measured: Up to 26 weeks
Progression-free Survial
Will be estimated using the product-limit method of Kaplan and Meier. Progression defined using RECIST v1.0 criteria, at least a 20% increase in the sum of the longest diameter of target lesions, or the appearance of one or more new lesions.
Measured: assessed up to 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2006 (estimated)
- Study startJun 2006
- Primary completionDec 2010
- Study completionDec 2010
Why it stopped: Trial stopped early for futility
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Localized Transitional Cell Cancer of the Renal Pelvis and UreterStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- David Quinn, MD, Principal investigator, University of Southern California, Norris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00363883
- Sponsor's protocol ID
- NCI-2012-02844
- Other IDs
- NCI-2012-02844, PHII-61, 6879, N01CM62209, P30CA033572
- Status last verified
- Jan 2014
- First submitted
- 10 Aug 2006
- Last updated
- 13 Feb 2015
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Quinn DI, Tsao-Wei DD, Twardowski P, Aparicio AM, Frankel P, Chatta G, Wright JJ, Groshen SG, Khoo S, Lenz HJ, Lara PN, Gandara DR, Newman E. Phase II study of the histone deacetylase inhibitor vorinostat (Suberoylanilide Hydroxamic Acid; SAHA) in recurrent or metastatic transitional cell carcinoma of the urothelium - an NCI-CTEP sponsored: California Cancer Consortium trial, NCI 6879. Invest New Drugs. 2021 Jun;39(3):812-820. doi: 10.1007/s10637-020-01038-6. Epub 2021 Jan 6.
PubMed 33409898
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Oral Suberoylanilide Hydroxamic Acid (SAHA) in Recurrent or Metastatic Transitional Cell Carcinoma of the Urothelium
- ClinicalTrials.gov ID
- NCT00363883
- Acronym / sponsor ID
- NCI-2012-02844
- Conditions
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Trial stopped early for futility
- Enrolment
- 14 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jun 2006
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 15 Aug 2006 (estimated)
- Results
- Posted 13 Feb 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- To determine response rate measured by RECIST criteria for SAHA in patients with recurrent or metastatic transitional cell carcinoma of the urothelium.
SECONDARY OBJECTIVES:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (vorinostat) | Experimental | Drug: vorinostat, Other: laboratory biomarker analysisPatients receive oral vorinostat (SAHA) twice daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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%)
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| vorinostatAlso: L-001079038, SAHA, suberoylanilide hydroxamic acid, ZolinzaGiven orally | Drug | Treatment (vorinostat) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (vorinostat) |
Primary outcome
Objective Tumor Response Rate
Time frame: Response assessed after every 2 cycles (6 weeks) up to 26 weeks
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
2 secondary outcomes
Overall Survival
Time frame: Up to 26 weeks
Progression-free Survial
Time frame: assessed up to 26 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33409898Quinn DI, Tsao-Wei DD, Twardowski P, Aparicio AM, Frankel P, Chatta G, Wright JJ, Groshen SG, Khoo S, Lenz HJ, Lara PN, Gandara DR, Newman E. Phase II study of the histone deacetylase inhibitor vorinostat (Suberoylanilide Hydroxamic Acid; SAHA) in recurrent or metastatic transitional cell carcinoma of the urothelium - an NCI-CTEP sponsored: California Cancer Consortium trial, NCI 6879. Invest New Drugs. 2021 Jun;39(3):812-820. doi: 10.1007/s10637-020-01038-6. Epub 2021 Jan 6.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Quinn, MD principal investigator
University of Southern California, Norris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing vorinostat and laboratory biomarker analysis in people with Localized Transitional Cell Cancer of the Renal Pelvis and Ureter and Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Feb 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Tumor Response Rate (time frame: Response assessed after every 2 cycles (6 weeks) up to 26 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00363883, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2015.