Efficacy and Safety Study of Panobinostat in Participants With Metastatic Hormone Refractory Prostate Cancer

Study Overview
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Brief Summary
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This Phase II single dose study was designed to characterize the safety, tolerability, and efficacy of intravenous (i.v.) panobinostat as a single-agent treatment in participants with hormone refractory prostate cancer.

Official Title
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A Phase II, Open Label, Single Arm Study of i.v. Panobinostat (LBH589) in Patients With Metastatic Hormone Refractory Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Panobinostat


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Confirmed diagnosis of adenocarcinoma of the prostate Participants with metastatic hormone refractory prostate cancer Participants that have had at least one, but not more than two prior cytotoxic treatments for prostate cancer Evidence of disease progression by at least one of the following: two or more lesions on bone scan progressive measurable disease two documented increases in prostate-specific antigen (PSA) Willing to use contraception throughout the study and for 12 weeks after study completion Exclusion criteria: History or clinical signs of central nervous system (CNS) disease History of other cancers not curatively treated with no evidence of disease for more than 5 years Prior radiotherapy within 3 weeks of starting study treatment Prior radiopharmaceuticals (strontium, samarium) Impaired cardiac function Heart disease Liver or renal disease with impaired function Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Panobinostat<br>Participants with metastatic hormone refractory prostate cancer received 20 milligrams per meter square (mg/m^2) of panobinostat intravenously (i.v.) on Days 1 and 8 of a 21-day cycle. Treatment continued until disease progression as per investigator, intolerable toxicity, start of new cancer therapy, death, or withdrawal of consent. | Drug: Panobinostat<br> <br> * Other names: LBH589;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Progression-Free Survival (PFS) Rate at 24 Weeks | The PFS rate was defined as the percentage of participants that were alive without documented disease progression at the end of 24 weeks from first study treatment. Disease Progression as per response evaluation criteria in solid tumors (RECIST) criteria: Measurable lesions: If target lesion was lymph node then it had to be at least 2 centimeter (cm) at baseline to assess change in size. Bone lesions: (non-target lesions) appearance of greater than or equal to (>=) 2 unequivocal new lesions confirmed on a second scan at least 6 weeks later. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Tumor Response Rate | The tumor response rate was defined as a percentage of participants with confirmed Complete Response (CR) or Partial Response (PR) per RECIST criteria. CR: Disappearance of all target lesions and all nontarget lesions. PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters. | Every 12 weeks up to approximately 2.7 years | 
| Percentage of Participants With Duration of Stable Disease (SD) Per RECIST | Duration of SD was the time from date of start of treatment to the date of event, defined as the first documented disease progression or death due to underlying cancer. Disease Progression as per RECIST criteria: Measurable lesions: If target lesion was lymph node then it had to be at least 2 cm at baseline to assess change in size. Bone lesions: (non-target lesions) appearance of >=2 unequivocal new lesions confirmed on a second scan at least 6 weeks later. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. CR: Disappearance of all target lesions and all nontarget lesions. PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters. If a participant had not had an event, duration of SD was to be censored at the date of last assessment. | Every 12 weeks up to approximately 2.7 years | 
| Percentage of Participants With Prostate Specific Antigen (PSA) Response Rate at 24 Weeks | The PSA response was defined as a 50% decrease in PSA from baseline maintained for >= 4 weeks, and without clinical or radiographic evidence of disease progression during this time period. Disease Progression as per RECIST criteria: Measurable lesions: If target lesion was lymph node then it had to be at least 2 cm at baseline to assess change in size. Bone lesions: (non-target lesions) appearance of >= 2 unequivocal new lesions confirmed on a second scan at least 6 weeks later. | 24 weeks | 
| Percentage of Participants With PSA Progression Rate at 24 Weeks | The PSA progression was defined as a 50% rise from nadir and a minimum rise of 2 nanogram per milligram (ng/mL). Disease Progression as per RECIST criteria: Measurable lesions: If target lesion was lymph node then it had to be at least 2 cm at baseline to assess change in size. Bone lesions: (non-target lesions) appearance of >=2 unequivocal new lesions confirmed on a second scan at least 6 weeks later. | 24 weeks | 
| Median Progression-free Survival (PFS) | PFS was defined as the time from the date of start of treatment to the date of first documented disease progression or death due to any cause. If a participant had not had a disease progression and was alive, the participant was to be censored using the RECIST. Disease Progression as per RECIST criteria: Measurable lesions: If target lesion was lymph node then it had to be at least 2 cm at baseline to assess change in size. Bone lesions: (non-target lesions) appearance of >=2 unequivocal new lesions confirmed on a second scan at least 6 weeks later. Kaplan-Meier method was to be used to estimate the median PFS. | After every cycle up to approximately 2.7 years | 
| Overall Survival | The overall survival was defined as the time from date of start of treatment to date of death due to any cause. If a participant was not known to have died, survival was to be censored at the date of last contact. Kaplan-Meier method was to be used to estimate overall survival. | Start of study treatment to date of death due to any cause (Up to approximately 2.7 years) | 
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality. | From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate, Cancer, Adenocarcinoma, Prostate-Specific Antigen, metastatic, male, HRPC, DACi