Back to resultsEfficacy and Safety Study of Panobinostat in Participants With Metastatic Hormone Refractory Prostate Cancer
Primary Purpose
Prostate Cancer
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Panobinostat
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring Prostate, Cancer, Adenocarcinoma, Prostate-Specific Antigen, metastatic, male, HRPC, DACi
Eligibility Criteria
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.
Sites / Locations
- University of Maryland
- Johns Hopkins Hospital
- Washington University
- Memorial Sloan Kettering Cancer Center
- University of Wisconsin
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Panobinostat
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00667862
Brief Title
Efficacy and Safety Study of Panobinostat in Participants With Metastatic Hormone Refractory Prostate Cancer
Official Title
A Phase II, Open Label, Single Arm Study of i.v. Panobinostat (LBH589) in Patients With Metastatic Hormone Refractory Prostate Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
March 18, 2008 (Actual)
Primary Completion Date
November 5, 2010 (Actual)
Study Completion Date
November 5, 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
Prostate, Cancer, Adenocarcinoma, Prostate-Specific Antigen, metastatic, male, HRPC, DACi
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Panobinostat
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Panobinostat
Other Intervention Name(s)
LBH589
Primary Outcome Measure Information:
Title
Percentage of Participants With Progression-Free Survival (PFS) Rate at 24 Weeks
Description
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.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Percentage of Participants With Tumor Response Rate
Description
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.
Time Frame
Every 12 weeks up to approximately 2.7 years
Title
Percentage of Participants With Duration of Stable Disease (SD) Per RECIST
Description
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.
Time Frame
Every 12 weeks up to approximately 2.7 years
Title
Percentage of Participants With Prostate Specific Antigen (PSA) Response Rate at 24 Weeks
Description
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.
Time Frame
24 weeks
Title
Percentage of Participants With PSA Progression Rate at 24 Weeks
Description
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.
Time Frame
24 weeks
Title
Median Progression-free Survival (PFS)
Description
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.
Time Frame
After every cycle up to approximately 2.7 years
Title
Overall Survival
Description
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.
Time Frame
Start of study treatment to date of death due to any cause (Up to approximately 2.7 years)
Title
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
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.
Time Frame
From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years)
10. Eligibility
Sex
Male
Gender Based
Yes
Gender Eligibility Description
Only male participants are eligible as it is a prostate cancer study.
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63130
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
University of Wisconsin
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53706-1481
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
23820963
Citation
Rathkopf DE, Picus J, Hussain A, Ellard S, Chi KN, Nydam T, Allen-Freda E, Mishra KK, Porro MG, Scher HI, Wilding G. A phase 2 study of intravenous panobinostat in patients with castration-resistant prostate cancer. Cancer Chemother Pharmacol. 2013 Sep;72(3):537-44. doi: 10.1007/s00280-013-2224-8. Epub 2013 Jul 3.
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Efficacy and Safety Study of Panobinostat in Participants With Metastatic Hormone Refractory Prostate Cancer
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