Prostate Cancer
Conditions
Keywords
Prostate, Cancer, Adenocarcinoma, Prostate-Specific Antigen, metastatic, male, HRPC, DACi
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.
Interventions
DRUGPanobinostat
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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: 1. two or more lesions on bone scan 2. progressive measurable disease 3. 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Progression-Free Survival (PFS) Rate at 24 Weeks | 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Duration of Stable Disease (SD) Per RECIST | Every 12 weeks up to approximately 2.7 years | 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 | 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 | 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. |
| Percentage of Participants With Tumor Response Rate | Every 12 weeks up to approximately 2.7 years | 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. |
| Overall Survival | Start of study treatment to date of death due to any cause (Up to approximately 2.7 years) | 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) | From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) | 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. |
| Median Progression-free Survival (PFS) | After every cycle up to approximately 2.7 years | 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. |
Countries
United States
Participant flow
Recruitment details
A total of 35 participants were enrolled in the study at 8 centers in 2 countries- Canada (3 sites) and the United states (5 sites) from 18 March 2008 to 05 November 2010.
Participants by arm
| Arm | Count |
|---|---|
| Panobinostat Participants with metastatic hormone refractory prostate cancer received 20 mg/m\^2 of panobinostat 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. | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 9 |
| Overall Study | Death | 1 |
| Overall Study | Disease Progression | 22 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Panobinostat |
|---|---|
| Age, Continuous | 68.1 years STANDARD_DEVIATION 9.41 |
| Sex/Gender, Customized Male | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 35 |
| other Total, other adverse events | 34 / 35 |
| serious Total, serious adverse events | 14 / 35 |
Outcome results
Primary
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.
Time frame: 24 weeks
Population: FAS population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panobinostat | Percentage of Participants With Progression-Free Survival (PFS) Rate at 24 Weeks | 11.4 percentage of participants |
Secondary
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.
Time frame: After every cycle up to approximately 2.7 years
Population: We have exhausted all efforts to locate this data and it has since been destroyed, therefore no data is available to report for this outcome measure.
Secondary
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.
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)
Population: Safety set population included all participants who were randomized and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Panobinostat | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 35 Participants |
| Panobinostat | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 14 Participants |
Secondary
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.
Time frame: Start of study treatment to date of death due to any cause (Up to approximately 2.7 years)
Population: We have exhausted all efforts to locate this data and it has since been destroyed, therefore no data is available to report for this outcome measure.
Secondary
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.
Time frame: Every 12 weeks up to approximately 2.7 years
Population: We have exhausted all efforts to locate this data and it has since been destroyed, therefore no data is available to report for this outcome measure.
Secondary
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.
Time frame: 24 weeks
Population: FAS population included all participants who received at least 1 dose of study drug. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panobinostat | Percentage of Participants With Prostate Specific Antigen (PSA) Response Rate at 24 Weeks | 0 percentage of participants |
Secondary
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.
Time frame: 24 weeks
Population: FAS population included all participants who received at least 1 dose of study drug. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panobinostat | Percentage of Participants With PSA Progression Rate at 24 Weeks | 48.6 percentage of participants |
Secondary
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.
Time frame: Every 12 weeks up to approximately 2.7 years
Population: FAS population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panobinostat | Percentage of Participants With Tumor Response Rate | 0 percentage of participants |