Recurrent Prostate CancerPhase 2NCT00330161
Vorinostat in Treating Patients With Progressive Metastatic Prostate Cancer
A Phase 2 study testing vorinostat and laboratory biomarker analysis in people with Recurrent Prostate Cancer and Stage IV Prostate Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase II trial is studying how well vorinostat works in treating patients with progressive metastatic prostate cancer. Drugs used in chemotherapy, such as vorinostat, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Recurrent Prostate Cancer, Stage IV Prostate Cancer
- 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
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2006to May 2011
- 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
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A histologic or cytologic diagnosis of prostate cancer
- Metastatic prostate cancer with measurable and/or bony disease that has progressed despite androgen deprivation therapy and one prior chemotherapy for castrate metastatic disease; all patients must have PSA progression defined as:
- At least 2 rises in PSA to be documented over a reference value (measure 1); the first rising PSA (measure 2) must be taken at least 7 days after the reference value; a third confirmatory PSA measure is required to be greater than the second measure and must be obtained at least 7 days after the 2nd measure; if this is not the case, a fourth PSA is required to be taken and be greater then the 2nd measure
- All patients must have a minimum PSA of >= 5 ng/ml
- ECOG performance status of 0-2
- Testosterone < 50 ng/dL; patients must continue primary androgen deprivation with an LHRH analogue if they have not undergone orchiectomy
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- No investigational or commercial agents (other than LHRH analogue) or therapies including other hormonal agents such as megestrol acetate (unless low dose given for hot flashes), antiandrogens or herbal medications may be administered with the intent to treat the patient's malignancy
- Four weeks must have elapsed since major surgery
- Prior radiotherapy is allowed as long as the bone marrow function is adequate and at least 4 weeks has elapsed since completion of radiation; no prior radiopharmaceuticals are allowed
- Life expectancy of greater than 6 months
- Ability to understand and the willingness to sign a written informed consent document that is approved by the Institutional Human Investigation Committee (HIC)
- Patients must have normal organ and marrow function as defined below obtained within two weeks from treatment initiation:
- Leukocytes >= 3,000/mcL
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL
- Serum creatinine < 2 mg/DL
- Total bilirubin within normal institutional limits
- AST/ALT =< 2.5 X institutional upper limit of normal
- Patients must be willing to provide blood samples for the correlative studies and consent to providing paraffin blocks/slides from primary prostate cancer or other prior diagnostic samples; fresh tissue sample donation is optional
- The effects of SAHA on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because HDAC inhibitors are known to be teratogenic, 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
- Patients with treated and controlled epidural disease are permitted into the study
Who cannot join
- Significant cardiovascular disease including congestive heart failure (New York Heart Association Class III or IV), active angina pectoris or recent myocardial infarction (within the last 6 months)
- Patients on Valproic Acid (a histone deacetylase inhibitor) must have stopped taking it at least 2 weeks prior to registration
- Oral anti-androgens must be stopped; no washout period is necessary prior to enrollment if anti-androgens were used as second line therapy and not as part of combined androgen deprivation; in the unlikely case that a patient may have continued on antiandrogen therapy as part of combined androgen deprivation and has never had antiandrogen withdrawal despite progression on combined androgen deprivation then a washout period will be needed (4 weeks for flutamide and 6 weeks for bicalutamide or nilutamide) prior to study enrollment
- Patients who have developed progression as defined in this protocol on stable doses of oral corticosteroids are eligible; the steroids may be continued
- No "currently active" second malignancy other than non-melanoma skin cancer; patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be with no evidence of disease
- 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; however, brain scans will not be required as part of the pre-study workup
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- History of allergic reactions attributed to compounds of similar chemical or biologic composition to SAHA
- 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; patients with history of HIV receiving combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with SAHA; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy
- Patients with the following history or clinical findings require ADDITIONAL diagnostic TESTING:
- Patients who require diuretics for reasons other than hypertension, digoxin for reasons other than atrial fibrillation, or patients with a history of mild to moderate congestive heart failure
- Patients with the following EKG results:
- Significant q waves (greater than 3 mm or greater than 1/3 the height of the QRS complex
- ST elevation or depressions of greater than 2 mm that are not attributable to hypertension strain
- The absence of a regular sinus rhythm
- The presence of a bundle block
- ADDITIONAL TESTING: (if required)
- Radionuclide angiocardiography (RNCA): Patients can be treated if the ejection fraction is > 45% and there is no evidence of ventricular aneurysm or other abnormal wall motion; patients with an ejection fraction < 45% on RNCA, with a worrisome but nonexclusive cardiovascular history, or an abnormal ECG as described above should also have a thallium stress test
- STRESS TEST RESULTS:
- Reversible defect - Exclude
- Fixed defect alone - Include
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Evaluation of Suberoylanilide Hydroxamic Acid (NSC 701852) in Patients With Advanced Prostate Cancer That Has Progressed on One Prior Chemotherapy
This phase II trial is studying how well vorinostat works in treating patients with progressive metastatic prostate cancer. Drugs used in chemotherapy, such as vorinostat, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the efficacy of oral SAHA in patients with castrate metastatic prostate cancer who have progressed on one prior chemotherapy, as measured by the proportion of patients not progressed at 6 months.
SECONDARY OBJECTIVES:
- To evaluate the safety of oral SAHA in patients with castrate metastatic prostate cancer who have progressed on one prior chemotherapy.
II. To assess the objective response rate of oral SAHA in patients with measurable disease when present.
III. To assess the rate of PSA decline of >= 50%. IV. To assess progression free and median survival in patients with castrate metastatic prostate cancer who have progressed on one prior chemotherapy.
- To evaluate pre and post-treatment tumor biopsies when available for the presence of changes in the expression of AR and Hsp90 client proteins, Thioredoxin, Thioredoxin Binding Protein, HDAC 3 (class I), HDAC 7 (class II), EZH2 and p21 expression.
VI. To determine the effects of oral SAHA on IL-6, soluble IL-6 receptor and soluble gp130 levels in the blood.
VII. To determine the accumulation and biodistribution of 18FDHT and correlate these findings with standard FDG PET, radionuclide bone scan, CT and/or MRI scans, as well as 18FDHT pharmacokinetics and tumor tissue staining for androgen receptor (AR) and Hsp90 client proteins (this applies only to patients at MSKCC under a separate protocol #00-095).
OUTLINE: This is a multicenter study.
Patients receive oral vorinostat (SAHA) once daily on days 1-21. Treatment repeats every 21 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response (CR) after 4 courses receive an additional 3 courses. All other patients may continue treatment in the absence of disease progression or unacceptable toxicity.
Blood samples are taken on day 15 of course 1, day 1 of course 2, during the last week of course 4, and at completion of study treatment. Blood is examined for interleukin (IL)-6, IL-6 receptor, and gp130 levels.
After completion of study treatment, patients are followed periodically for survival.
- Being tested
- vorinostat, laboratory biomarker analysis
- Medical subject headings
- Prostatic Neoplasms
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) once daily on days 1-21. Treatment repeats every 21 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response (CR) after 4 courses receive an additional 3 courses. All other patients may continue treatment in the absence of disease progression or unacceptable toxicity.
Blood samples are taken on day 15 of course 1, day 1 of course 2, during the last week of course 4, and at completion of study treatment. Blood is examined for interleukin (IL)-6, IL-6 receptor, and gp130 levels. Receives: Drug: vorinostat; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Patients Who do Not Demonstrate Disease Progression
Fisher's Exact Test will be used.
Measured: At 6 months
Secondary outcomes (5)
Incidence of Toxicity
The percentage of eligible participants that experience grade 3 or 4 toxicities.
Measured: Up to 3 years
Rate of PSA Decline
Rate of Prostate Specific Antigen (PSA) decline of greater than or equal to 50%.
Measured: Up to 3 years
Progression-free Survival
Median time to progression was determined.
Measured: From the start of treatment to time of progression, assessed up to 3 years
Median Survival
Median overall survival.
Measured: Up to 3 years
Objective Response Rate
Percentage of participants that obtain the best objective response, stable disease.
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2006 (estimated)
- Study startMar 2006
- Primary completionSep 2009
- Study completionMay 2011
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.
- Other trials for Recurrent Prostate CancerStudies 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
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Maha Hussain, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00330161
- Sponsor's protocol ID
- NCI-2012-03067
- Other IDs
- NCI-2012-03067, UMCC 2005.127, 6862, N01CM62206, N01CM62201, U01CA062491, P30CA046592
- Status last verified
- Dec 2012
- First submitted
- 25 May 2006
- Last updated
- 26 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Evaluation of Suberoylanilide Hydroxamic Acid (NSC 701852) in Patients With Advanced Prostate Cancer That Has Progressed on One Prior Chemotherapy
- ClinicalTrials.gov ID
- NCT00330161
- Acronym / sponsor ID
- NCI-2012-03067
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Mar 2006
- Primary completion
- Sep 2009 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 26 May 2006 (estimated)
- Results
- Posted 26 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial is studying how well vorinostat works in treating patients with progressive metastatic prostate cancer. Drugs used in chemotherapy, such as vorinostat, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES:
- To evaluate the efficacy of oral SAHA in patients with castrate metastatic prostate cancer who have progressed on one prior chemotherapy, as measured by the proportion of patients not progressed at 6 months.
SECONDARY OBJECTIVES:
- To evaluate the safety of oral SAHA in patients with castrate metastatic prostate cancer who have progressed on one prior chemotherapy.
II. To assess the objective response rate of oral SAHA in patients with measurable disease when present.
III. To assess the rate of PSA decline of >= 50%. IV. To assess progression free and median survival in patients with castrate metastatic prostate cancer who have progressed on one prior chemotherapy.
- To evaluate pre and post-treatment tumor biopsies when available for the presence of changes in the expression of AR and Hsp90 client proteins, Thioredoxin, Thioredoxin Binding Protein, HDAC 3 (class I), HDAC 7 (class II), EZH2 and p21 expression.
VI. To determine the effects of oral SAHA on IL-6, soluble IL-6 receptor and soluble gp130 levels in the blood.
VII. To determine the accumulation and biodistribution of 18FDHT and correlate these findings with standard FDG PET, radionuclide bone scan, CT and/or MRI scans, as well as 18FDHT pharmacokinetics and tumor tissue staining for androgen receptor (AR) and Hsp90 client proteins (this applies only to patients at MSKCC under a separate protocol #00-095).
OUTLINE: This is a multicenter study.
Patients receive oral vorinostat (SAHA) once daily on days 1-21. Treatment repeats every 21 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response (CR) after 4 courses receive an additional 3 courses. All other patients may continue treatment in the absence of disease progression or unacceptable toxicity.
Blood samples are taken on day 15 of course 1, day 1 of course 2, during the last week of course 4, and at completion of study treatment. Blood is examined for interleukin (IL)-6, IL-6 receptor, and gp130 levels.
After completion of study treatment, patients are followed periodically for survival.
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) once daily on days 1-21. Treatment repeats every 21 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response (CR) after 4 courses receive an additional 3 courses. All other patients may continue treatment in the absence of disease progression or unacceptable toxicity. Blood samples are taken on day 15 of course 1, day 1 of course 2, during the last week of course 4, and at completion of study treatment. Blood is examined for interleukin (IL)-6, IL-6 receptor, and gp130 levels. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- A histologic or cytologic diagnosis of prostate cancer
- Metastatic prostate cancer with measurable and/or bony disease that has progressed despite androgen deprivation therapy and one prior chemotherapy for castrate metastatic disease; all patients must have PSA progression defined as:
- All patients must have a minimum PSA of >= 5 ng/ml
- ECOG performance status of 0-2
- Testosterone < 50 ng/dL; patients must continue primary androgen deprivation with an LHRH analogue if they have not undergone orchiectomy
Key exclusion criteria (20 listed)
- Significant cardiovascular disease including congestive heart failure (New York Heart Association Class III or IV), active angina pectoris or recent myocardial infarction (within the last 6 months)
- Patients on Valproic Acid (a histone deacetylase inhibitor) must have stopped taking it at least 2 weeks prior to registration
- Oral anti-androgens must be stopped; no washout period is necessary prior to enrollment if anti-androgens were used as second line therapy and not as part of combined androgen deprivation; in the unlikely case that a patient may have continued on antiandrogen therapy as part of combined androgen deprivation and has never had antiandrogen withdrawal despite progression on combined androgen deprivation then a washout period will be needed (4 weeks for flutamide and 6 weeks for bicalutamide or nilutamide) prior to study enrollment
- Patients who have developed progression as defined in this protocol on stable doses of oral corticosteroids are eligible; the steroids may be continued
- No "currently active" second malignancy other than non-melanoma skin cancer; patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be with no evidence of disease
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
Proportion of Patients Who do Not Demonstrate Disease Progression
Time frame: At 6 months
Fisher's Exact Test will be used.
5 secondary outcomes
Incidence of Toxicity
Time frame: Up to 3 years
Rate of PSA Decline
Time frame: Up to 3 years
Progression-free Survival
Time frame: From the start of treatment to time of progression, assessed up to 3 years
Median Survival
Time frame: Up to 3 years
Objective Response Rate
Time frame: Up to 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Maha Hussain principal investigator
University of Michigan
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 Recurrent Prostate Cancer and Stage IV Prostate Cancer, 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 21 inclusion and 20 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: finished, as of the sponsor's last update on 26 May 2014. 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 26 May 2014). 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?
Proportion of Patients Who do Not Demonstrate Disease Progression (time frame: At 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 May 2014.