Safety and Efficacy Studies of Panobinostat and Bicalutamide in Patients With Recurrent Prostate Cancer After Castration

NCT00878436 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 08-479
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 4

Brief 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. As of July 23, 2013 Arm B was closed to accrual, all the remaining slots in accrual will be allocated to Arm A.

Conditions

Prostate Cancer; Prostatic Neoplasms

Keywords

histone deacetylase inhibitor; hormone therapy; androgen-independent; PSA; androgen receptor

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  6 months

Secondary Outcomes (2)

• Time to PSA Progression

  up to 2 years

• Number of Patients That Achieve a 50% or Greater PSA Decline by 9 Months of Therapy

  9 months

Study Arms (2)

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

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

Drug: Panobinostat; Drug: Bicalutamide

Interventions

Panobinostat DRUG

Also known as: LBH589

Arm A (120 mg/week); Arm B (60 mg/week)-Closed to accrual

Bicalutamide DRUG

Also known as: Casodex

Arm A (120 mg/week); Arm B (60 mg/week)-Closed to accrual

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• NYU Langone Health: lead
• Novartis: collaborator

Study Sites (4)

The Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

North Shore University Hospital-Monter Cancer Center

Lake Success, New York, 11042, United States

Location

NYU Cancer Center

New York, New York, 10016, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Bulbo-Spinal Atrophy, X-Linked

Interventions

Panobinostat; bicalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Muscular Atrophy, Spinal; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Motor Neuron Disease; Neuromuscular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Fraustina Hsu
• Organization: NYU Langone Medical Center

fraustina.hsu@nyumc.org

646 754 712

Study Officials

• Anna Ferrari, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2009
• First Posted: April 9, 2009
• Study Start: June 1, 2009
• Primary Completion: March 1, 2015
• Study Completion: July 1, 2015
• Last Updated: February 7, 2018
• Results First Posted: December 4, 2017

Record last verified: 2018-01

Locations

US (4)