Vorinostat in Treating Patients With Progressive Metastatic Prostate Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 4 March 2013
• Main ID: NCT00330161
• Date of registration: 25/05/2006
• Primary sponsor: National Cancer Institute (NCI)
• Public title: Vorinostat in Treating Patients With Progressive Metastatic Prostate Cancer
• Scientific title: Phase II Evaluation of Suberoylanilide Hydroxamic Acid (NSC 701852) in Patients With Advanced Prostate Cancer That Has Progressed on One Prior Chemotherapy
• Date of first enrolment: March 2006
• Target sample size: 29
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00330161
• Study type: Interventional
• Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Maha Hussain
• Affiliation: University of Michigan University Hospital

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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

- 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

Exclusion Criteria:

- 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

- 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



Age minimum: 18 Years
Age maximum: N/A
Gender: Male

Health Condition(s) or Problem(s) studied

Recurrent Prostate Cancer

Stage IV Prostate Cancer

Intervention(s)

Drug: vorinostat

Other: laboratory biomarker analysis

Primary Outcome(s)

Proportion of patients who do not demonstrate disease progression [Time Frame: At 6 months]

Secondary Outcome(s)

Incidence of toxicity [Time Frame: Up to 3 years]

Median survival [Time Frame: Up to 3 years]

Objective response rate [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]

Rate of PSA decline [Time Frame: Up to 3 years]

Secondary ID(s)

N01CA62491

N01CM62201

N01CM62206

NCI-2012-03067

UMCC 2005.127

Source(s) of Monetary Support

Please refer to primary and secondary sponsors