Prostate Cancer
Conditions
Keywords
Hormone-refractory, prostate cancer, multitargeted, tyrosinkinase
Brief summary
The purpose of this study is to evaluate the efficacy, tolerability and safety of a multi-targeted therapy in patients with hormone-refractory prostate cancer.
Interventions
DRUGimatinib mesylate
DRUGTreosulfane
DRUGetoricoxib
DRUGpioglitazone
DRUGdexamethasone
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
* Histologically confirmed prostate carcinoma, which has proven progression after primary hormone therapy (surgical or medicinal castration). * Patients must have increasing PSA levels (within 3 months prior to enrollment) with at least two consecutively increasing PSA levels. * PSA value before inclusion must be at least 5 ng/ml * At least 18 years of age. * At least capable of self care and up of at least 50% of waking hours (ECOG performance status 0 - 2), adequate bone marrow function and lab results.
Exclusion criteria
* Change of hormone therapy within 6 weeks prior inclusion * Prior chemotherapy * Therapy with Imatinib, or therapy with other inhibitors of tyrosinkinase. * Second neoplasm diagnosed within 5 years before study start. * Patients who require therapy with warfarin * Known diagnosis of HIV, hepatitis B, or hepatitis C infection. * Severe, unstable, or uncontrolled medical disease which would confound diagnoses or evaluations required by the protocol, including severe cardiac insufficiency * Surgical therapy within 4 weeks before inclusion. * Prior therapy with isotopes strontium or rhenium. * Radiation therapy to \> 25% of bone marrow within 4 weeks before inclusion. * Treatment with other experimental substances within 30 days before study start. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PSA Response Rate | up to 24 weeks | To investigate the effect of a treatment with Imatinib mesylate, Pioglitazone , Etoricoxib, and Dexamethasone in combination with metronomic chemotherapy (Treosulfane) on the PSA response rate in patients with hormone refractory prostate cancer. A patient will be defined as a responder if a PSA decline of at least 50%, which must be confirmed by a second PSA value 4 weeks later, is observed. A patient will be defined as a non-responder if PSA has not decreased during treatment. Non-response is defined as a 25% increase over the baseline on-study which is confirmed (equal or more) by a second value 4 weeks apart. The absolute increase must account for \> 5 ng/ml. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to PSA Response | every 4 weeks up to 24 weeks | Time to PSA response, defined as the time from first administration of study drugs to the first PSA value of a confirmed PSA response. Non-responders will be censored with date of final visit/premature discontinuation for the analysis. Median time to PSA response was not achieved |
| Time to Progression-free Survival | every 4 weeks up to 24 weeks | Progression-free survival, defined as the time from first administration of study drugs to the first PSA value of a PSA non-responder. Responders will be censored with date of PSA response for the analysis. The median time to PSA progression free survival was not achieved |
| Overall Survival Rate | every 4 weeks up to 24 weeks | Overall survival (OS) is defined as time from randomization to death from any cause or last date known alive. The median time to overall survival rate was not achieved |
| Quality of Life Assessed With EORTC-30 | baseline and Final Visit (week 24) | Health-related quality of life was assessed with the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-30) questionnaire and was presented descriptively. The EORTC QLQ-C30 is a questionnaire including following sub-scales: global health status, functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social activity), symptom scales (fatigue, nausea and vomiting, and pain) and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhoea and financial difficulties). Scores are averaged for each scale and transformed to 0-100 scale; higher score indicates better quality of life on global health status and functional scales and worse quality of life on symptom scales and financial difficulty scale. |
Countries
Germany
Participant flow
Recruitment details
In 15 centers 72 patients were screened, 67 enrolled, of which 65 were treated and 33 completed the treatment phase. Intent to Treat (ITT) population included 61 patients. For the extension follow-up phase 19 patients were included in the safety analysis.
Participants by arm
| Arm | Count |
|---|---|
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane STI571 (imatinib) 400mg po daily + pioglitazone 60mg po daily + etoricoxib 60mg po daily + dexamethasone 1mg po daily + treosulfane 500mg po daily for 24 weeks | 65 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Abnormal laboratory values | 1 |
| Overall Study | Adverse Event | 6 |
| Overall Study | Death | 1 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Unsatisfactory therapeutic effect | 13 |
| Overall Study | Withdrawal by Subject | 9 |
Baseline characteristics
| Characteristic | STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane |
|---|---|
| Age, Continuous | 67 years STANDARD_DEVIATION 7 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 65 / 65 | 19 / 19 |
| serious Total, serious adverse events | 22 / 65 | 7 / 19 |
Outcome results
Primary
PSA Response Rate
To investigate the effect of a treatment with Imatinib mesylate, Pioglitazone , Etoricoxib, and Dexamethasone in combination with metronomic chemotherapy (Treosulfane) on the PSA response rate in patients with hormone refractory prostate cancer. A patient will be defined as a responder if a PSA decline of at least 50%, which must be confirmed by a second PSA value 4 weeks later, is observed. A patient will be defined as a non-responder if PSA has not decreased during treatment. Non-response is defined as a 25% increase over the baseline on-study which is confirmed (equal or more) by a second value 4 weeks apart. The absolute increase must account for \> 5 ng/ml.
Time frame: up to 24 weeks
Population: Intent to Treat (ITT) includes the 61 patients treated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | PSA Response Rate | PSA responder - No | 38 participants |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | PSA Response Rate | PSA responder - Yes | 23 participants |
Secondary
Overall Survival Rate
Overall survival (OS) is defined as time from randomization to death from any cause or last date known alive. The median time to overall survival rate was not achieved
Time frame: every 4 weeks up to 24 weeks
Population: Intent to Treat (ITT) includes the 61 patients treated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Overall Survival Rate | NA days |
Secondary
Quality of Life Assessed With EORTC-30
Health-related quality of life was assessed with the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-30) questionnaire and was presented descriptively. The EORTC QLQ-C30 is a questionnaire including following sub-scales: global health status, functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social activity), symptom scales (fatigue, nausea and vomiting, and pain) and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhoea and financial difficulties). Scores are averaged for each scale and transformed to 0-100 scale; higher score indicates better quality of life on global health status and functional scales and worse quality of life on symptom scales and financial difficulty scale.
Time frame: baseline and Final Visit (week 24)
Population: Intent to Treat (ITT) includes the 61 patients treated
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Baseline: financial difficulties (n=49) | 11.6 scores on a scale | Standard Deviation 16.03 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Baseline: appetite loss (n=50) | 16.0 scores on a scale | Standard Deviation 29.54 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Baseline: dyspnea (n=49) | 20.4 scores on a scale | Standard Deviation 27.06 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Baseline: constipation (n=50) | 14.0 scores on a scale | Standard Deviation 28.64 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Baseline: role functioning (n=50) | 74.0 scores on a scale | Standard Deviation 28.8 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Baseline: insomnia (n=49) | 34.0 scores on a scale | Standard Deviation 34.35 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Baseline: cognitive functioning (n=49) | 87.1 scores on a scale | Standard Deviation 16.41 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Baseline: diarrhea (n=50) | 9.3 scores on a scale | Standard Deviation 21.34 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Baseline: physical functioning (n=50) | 81.7 scores on a scale | Standard Deviation 17.19 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Baseline: pain (n=50) | 32.3 scores on a scale | Standard Deviation 32.89 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Baseline: emotional functioning (n=49) | 64.6 scores on a scale | Standard Deviation 21.89 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Baseline: social functioning (n=49) | 72.4 scores on a scale | Standard Deviation 26.69 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Baseline: fatigue (n=50) | 32.9 scores on a scale | Standard Deviation 26.08 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Baseline: global health status (n=49) | 60.0 scores on a scale | Standard Deviation 18.24 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Baseline: nausea & vomiting (n=50) | 26.0 scores on a scale | Standard Deviation 28.8 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Final Visit: financial difficulties (n=42) | 19.0 scores on a scale | Standard Deviation 28.65 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Final Visit: appetite loss (n=43) | 24.0 scores on a scale | Standard Deviation 33.59 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Final Visit: dyspnea (n=43) | 38.8 scores on a scale | Standard Deviation 29.03 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Final Visit: constipation (n=43) | 6.2 scores on a scale | Standard Deviation 15.01 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Final Visit: role functioning (n=43) | 55.4 scores on a scale | Standard Deviation 31.01 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Final Visit: insomnia (n=42) | 31.7 scores on a scale | Standard Deviation 32.05 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Final Visit: cognitive functioning (n=43) | 81.8 scores on a scale | Standard Deviation 20.51 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Final Visit: diarrhea (n=43) | 13.2 scores on a scale | Standard Deviation 23.16 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Final Visit: physical functioning (n=43) | 66.7 scores on a scale | Standard Deviation 25.32 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Final Visit: pain (n=43) | 26.0 scores on a scale | Standard Deviation 30.06 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Final Visit: emotional functioning (n=43) | 61.8 scores on a scale | Standard Deviation 28.42 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Final Visit: social functioning (n=43) | 64.0 scores on a scale | Standard Deviation 32.52 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Final Visit: fatigue (n=43) | 46.0 scores on a scale | Standard Deviation 29.05 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Final Visit: global health status (n=43) | 51.0 scores on a scale | Standard Deviation 21.76 |
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Quality of Life Assessed With EORTC-30 | Final Visit: nausea & vomiting (n=43) | 44.6 scores on a scale | Standard Deviation 31.01 |
Secondary
Time to Progression-free Survival
Progression-free survival, defined as the time from first administration of study drugs to the first PSA value of a PSA non-responder. Responders will be censored with date of PSA response for the analysis. The median time to PSA progression free survival was not achieved
Time frame: every 4 weeks up to 24 weeks
Population: Intent to Treat (ITT) includes the 61 patients treated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Time to Progression-free Survival | NA days |
Secondary
Time to PSA Response
Time to PSA response, defined as the time from first administration of study drugs to the first PSA value of a confirmed PSA response. Non-responders will be censored with date of final visit/premature discontinuation for the analysis. Median time to PSA response was not achieved
Time frame: every 4 weeks up to 24 weeks
Population: Intent to Treat (ITT) includes the 61 patients treated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| STI571+ Pioglitazone+ Etoricoxib + Dexamethasone + Treosulfane | Time to PSA Response | NA days |