Prostate CancerPhase 1/2NCT00878436
Safety and Efficacy Studies of Panobinostat and Bicalutamide in Patients With Recurrent Prostate Cancer After Castration
A Phase 1/2 study testing Panobinostat and Bicalutamide in people with Prostate Cancer and Prostatic Neoplasms, run by NYU Langone Health at 4 sites in United States.
Trial summary
This trial is designed to investigate the safety, dosing schedule, and efficacy of the combination treatment of Panobinostat (a histone deacetylase inhibitor) and hormone therapy for recurrent prostate cancer. This trial is at its Phase II stage. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer, Prostatic Neoplasms
- What is being tested?
- Panobinostat and Bicalutamide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 4 sitesUnited States
- Study dates
- Jun 2009to Jul 2015
- Phase
- Phase 1/2
- 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
- Male patients aged ≥ 18 years old
- Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
- Patients must meet laboratory criteria
- Baseline MUGA or ECHO must demonstrate LVEF ≥ the lower limit of the institutional normal.
- ECOG Performance Status of ≤ 2
- Documented history of adenocarcinoma of the prostate.
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- Patients must have evidence of disease progression while receiving androgen suppression therapy by orchiectomy or other primary hormonal therapy including, but not limited to (LHRH agonist therapy (e.g., leuprolide or goserelin) or LHRH antagonist (e.g. aberelix). Note: patients who have not undergone bilateral orchiectomy must continue LHRH therapy while on protocol
- Testosterone must be < 50 ng/dl confirmed within 4 weeks prior to registration for patients on LHRH therapy
- Patients must have evidence of disease progression with either one or both of the conditions listed:
- Biochemical progression only
- Metastases on bone scan
- Patients may have received one chemotherapy, investigational agent or immunotherapy in the neoadjuvant, adjuvant setting or during initial LHRH therapy with new evidence of disease progression after discontinuation of therapy for ≥ 2 weeks.
- Patients must have received one or more prior second line hormone therapy for progression while on LHRH treatment or orchiectomy.
- Patients treated with one first line chemotherapy combination for hormone refractory progression ≥ 4 weeks prior to registration who have evidence of disease progression and had only one second line hormone therapy and did not experience PSA response to bicalutamide (Casodex®) withdrawal.
Who cannot join
- Prior treatment with an HDAC inhibitor
- Impaired cardiac function including any one of the following:
- Screening ECG with a QTc > 450 msec confirmed by central laboratory prior to enrollment to the study
- Patients with congenital long QT syndrome
- History of sustained ventricular tachycardia
- Any history of ventricular fibrillation or torsades de pointes
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- Bradycardia defined as heart rate < 50 beats per minute. Patients with a pacemaker and heart rate ≥ 50 beats per minute are eligible.
- Patients with a myocardial infarction or unstable angina within 6 months of study entry
- Congestive heart failure (NY Heart Association class III or IV)
- Right bundle branch block in conjunction with left anterior hemi-block (bifasicular block)
- Uncontrolled hypertension
- Concomitant use of drugs with a risk of causing torsades de pointes
- Concomitant use of CYP3A4 inhibitors
- Patients with unresolved diarrhea greater than CTCAE grade 1
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LBH589
- Other concurrent severe and/or uncontrolled medical conditions
- Patients who have received chemotherapy, any investigational drug or undergone major surgery < 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
- Concomitant use of any anti-cancer therapy or radiation therapy.
- Male patients whose sexual partners are WOCBP not using effective birth control
- Patients with a history of another primary malignancy within the last 2 years that was not curatively treated, excluding basal or squamous cell carcinoma of the skin
- Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required
- Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
- Patients previously treated with bicalutamide (Casodex®) who experienced a PSA withdrawal response in the washout period as described in Inclusion #11 will not be eligible
- Concurrent use of estrogens or estrogen like substances (i.e. PC-SPES, Saw Palmetto, or other herbal product which may contain phytoestrogens) is not allowed. Prior use of these agents will need to be discontinued at least 4 weeks prior to enrollment, for the above.
- Radiotherapy within the 4 weeks prior to registration
- Inadequate bone marrow function measured 28 days prior to registration
- No serious concurrent medical illness or active infection that would jeopardize the ability of the patient to receive therapy as outlined in the protocol with reasonable safety.
- Liver metastasis.
- The use of bisphosphonates in the absence of metastasis will not be allowed. Patients on bisphosphonates for more than 4 weeks for asymptomatic bone metastasis and with continued evidence of PSA progression may continue on bisphosphonates every 4 weeks.
- Hydronephrosis with impaired renal function.
- Active spinal cord compression.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
North Shore University Hospital-Monter Cancer Center
Lake Success, New York, 11042
The Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
NYU Cancer Center
New York, New York, 10016
Oregon Health & Science University
Portland, Oregon, 97239
About this study
Official title: Phase I/II Randomized Trial of LBH589 (Panobinostat) at Two Dose Levels Combined With Bicalutamide (Casodex) in Men With Castration-resistant Prostate Cancer
This trial is designed to investigate the safety, dosing schedule, and efficacy of the combination treatment of Panobinostat (a histone deacetylase inhibitor) and hormone therapy for recurrent prostate cancer. This trial is at its Phase II stage. As of July 23, 2013 Arm B was closed to accrual, all the remaining slots in accrual will be allocated to Arm A.
Read the detailed description
The preclinical data indicate that Panobinostat restores the sensitivity of androgen-independent cells to bicalutamide (Casodex®) and the combination has synergistic inhibitory activity. Here, we hypothesize that treatment of castration-resistant patients with Panobinostat will enhance the response to the second line hormone therapy with bicalutamide (Casodex®). In the proposed phase I study, the maximum tolerated dose of tri-weekly, intermittent oral Panobinostat at three different dose levels (60, 90, 120 mg/week) in combination with Casodex (50mg PO) will be determined; The following phase II study will evaluated the efficacies of 9-month treatments of the selected Panobinostat-Casodex combination and also a lower dose of Panobinostat. We expect that Casodex-Panobinostat combination treatment of castration-resistant patients will prevent biochemical and/or metastatic disease progression of these patients compared to historical controls in the same time period.
- Conditions
- Prostate Cancer, Prostatic Neoplasms
- Being tested
- Panobinostat, Bicalutamide
- Keywords
- histone deacetylase inhibitor, hormone therapy, androgen-independent, PSA, androgen receptor
- Medical subject headings
- Prostatic Neoplasms, Bulbo-Spinal Atrophy, X-Linked
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PanobinostatDrug
Also called LBH589
BicalutamideDrug
Also called Casodex
| Study group | Role | What they receive |
|---|---|---|
| Arm A (120 mg/week) | Experimental | Each treatment cycle has 21 days:
Bicalutamide (Casodex®) 50mg P.O. daily, continuously, with the addition of:
40 mg Panobinostat 3 times per week (120 mg per week) for 2 consecutive weeks with one week rest Receives: Drug: Panobinostat; Drug: Bicalutamide |
| Arm B (60 mg/week)-Closed to accrual | Experimental | Each treatment cycle has 21 days:
Bicalutamide (Casodex®) 50mg P.O. daily, continuously, with the addition of:
20 mg Panobinostat 3 times per week (60 mg per week) for 2 consecutive weeks with one week rest Receives: Drug: Panobinostat; Drug: Bicalutamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Patients Free of Progression and Without Symptomatic Deterioration
measured by PSA and /or metastases progression criteria by body CT following RECIST criteria 1.1 and/or bones scan following the appearance of at least 2 new bone metastases and confirmation of 2 additional bone metastasis on a subsequent bone scan 6-8 weeks later and/or clinical progression.
Only participants who completed two or more treatment cycles were assessed for this outcome measure.
Measured: 9 months
Percentage of Patients Free of Progression and Without Symptomatic Deterioration
measured by PSA and /or metastases progression criteria by body CT following RECIST criteria 1.1 and/or bones scan following the appearance of at least 2 new bone metastases and confirmation of 2 additional bone metastasis on a subsequent bone scan 6-8 weeks later and/or clinical progression.
Only participants who completed two or more treatment cycles were assessed for this outcome measure.
Measured: 6 months
Secondary outcomes (2)
Time to PSA Progression
PSA progression is defined as a 25% or greater increase in PSA and an absolute increase value of 2 ng/ml or more over a nadir or baseline documented and confirmed by a second value three weeks later
Measured: up to 2 years
Number of Patients That Achieve a 50% or Greater PSA Decline by 9 Months of Therapy
Unable to locate PI for secondary outcome measure results. Data is not available.
Measured: 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2009 (estimated)
- Study startJun 2009
- Primary completionMar 2015
- Study completionJul 2015
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 Prostate CancerStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Anna Ferrari, MD, Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00878436
- Sponsor's protocol ID
- 08-479
- Status last verified
- Jan 2018
- First submitted
- 8 Apr 2009
- Last updated
- 7 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Randomized Trial of LBH589 (Panobinostat) at Two Dose Levels Combined With Bicalutamide (Casodex) in Men With Castration-resistant Prostate Cancer
- ClinicalTrials.gov ID
- NCT00878436
- Acronym / sponsor ID
- 08-479
- Conditions
- Prostate Cancer, Prostatic Neoplasms
- Keywords
- histone deacetylase inhibitor, hormone therapy, androgen-independent, PSA, androgen receptor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Jun 2009
- Primary completion
- Mar 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 9 Apr 2009 (estimated)
- Results
- Posted 4 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial is designed to investigate the safety, dosing schedule, and efficacy of the combination treatment of Panobinostat (a histone deacetylase inhibitor) and hormone therapy for recurrent prostate cancer. This trial is at its Phase II stage. As of July 23, 2013 Arm B was closed to accrual, all the remaining slots in accrual will be allocated to Arm A.
Detailed description
The preclinical data indicate that Panobinostat restores the sensitivity of androgen-independent cells to bicalutamide (Casodex®) and the combination has synergistic inhibitory activity. Here, we hypothesize that treatment of castration-resistant patients with Panobinostat will enhance the response to the second line hormone therapy with bicalutamide (Casodex®). In the proposed phase I study, the maximum tolerated dose of tri-weekly, intermittent oral Panobinostat at three different dose levels (60, 90, 120 mg/week) in combination with Casodex (50mg PO) will be determined; The following phase II study will evaluated the efficacies of 9-month treatments of the selected Panobinostat-Casodex combination and also a lower dose of Panobinostat. We expect that Casodex-Panobinostat combination treatment of castration-resistant patients will prevent biochemical and/or metastatic disease progression of these patients compared to historical controls in the same time period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A (120 mg/week) | Experimental | Drug: Panobinostat, Drug: BicalutamideEach treatment cycle has 21 days: Bicalutamide (Casodex®) 50mg P.O. daily, continuously, with the addition of: 40 mg Panobinostat 3 times per week (120 mg per week) for 2 consecutive weeks with one week rest |
| Arm B (60 mg/week)-Closed to accrual | Experimental | Drug: Panobinostat, Drug: BicalutamideEach treatment cycle has 21 days: Bicalutamide (Casodex®) 50mg P.O. daily, continuously, with the addition of: 20 mg Panobinostat 3 times per week (60 mg per week) for 2 consecutive weeks with one week rest |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Male patients aged ≥ 18 years old
- Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
- Patients must meet laboratory criteria
- Baseline MUGA or ECHO must demonstrate LVEF ≥ the lower limit of the institutional normal.
- ECOG Performance Status of ≤ 2
Key exclusion criteria (31 listed)
- Prior treatment with an HDAC inhibitor
- Impaired cardiac function including any one of the following:
- Uncontrolled hypertension
- Concomitant use of drugs with a risk of causing torsades de pointes
- Concomitant use of CYP3A4 inhibitors
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 |
|---|---|---|
| PanobinostatAlso: LBH589 | Drug | Arm A (120 mg/week), Arm B (60 mg/week)-Closed to accrual |
| BicalutamideAlso: Casodex | Drug | Arm A (120 mg/week), Arm B (60 mg/week)-Closed to accrual |
Primary outcome
Percentage of Patients Free of Progression and Without Symptomatic Deterioration
Time frame: 9 months
measured by PSA and /or metastases progression criteria by body CT following RECIST criteria 1.1 and/or bones scan following the appearance of at least 2 new bone metastases and confirmation of 2 additional bone metastasis on a subsequent bone scan 6-8 weeks later and/or clinical progression. Only participants who completed two or more treatment cycles were assessed for this outcome measure.
Percentage of Patients Free of Progression and Without Symptomatic Deterioration
Time frame: 6 months
measured by PSA and /or metastases progression criteria by body CT following RECIST criteria 1.1 and/or bones scan following the appearance of at least 2 new bone metastases and confirmation of 2 additional bone metastasis on a subsequent bone scan 6-8 weeks later and/or clinical progression. Only participants who completed two or more treatment cycles were assessed for this outcome measure.
2 secondary outcomes
Time to PSA Progression
Time frame: up to 2 years
Number of Patients That Achieve a 50% or Greater PSA Decline by 9 Months of Therapy
Time frame: 9 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2018.
- 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.
Anna Ferrari, MD principal investigator
NYU Langone Health
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Panobinostat and Bicalutamide in people with Prostate Cancer and Prostatic Neoplasms, run by NYU Langone Health at 4 sites 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 14 inclusion and 31 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 7 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 4 Dec 2017). 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?
Percentage of Patients Free of Progression and Without Symptomatic Deterioration (time frame: 9 months). The study lists 2 primary outcomes in all. 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 7 Feb 2018.