Combined Antiinflammatory and Angiostatic Therapy in Patients With Hormone-refractory Prostate Cancer

Study Overview
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Brief Summary
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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.

Official Title
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A Single Stage Phase II, Multi-centre, Open Label Study of Imatinib in Combination With Pioglitazone, Etoricoxib, Dexamethasone and Low-dose Treosulfane for Anti-inflammatory and Angiostatic Treatment in Patients With Hormone-refractory Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: imatinib mesylate
* Drug: Treosulfane
* Drug: etoricoxib
* Drug: pioglitazone
* Drug: dexamethasone


Participation Criteria
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Eligibility Criteria
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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/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: STI571+ pioglitazone+ etoricoxib + dexamethasone + treosulfane<br>STI571 (imatinib) 400mg po daily + pioglitazone 60mg po daily + etoricoxib 60mg po daily + dexamethasone 1mg po daily + treosulfane 500mg po daily for 24 weeks | Drug: imatinib mesylate<br> <br> * Other names: Glivec;Drug: Treosulfane<br> <br> * Other names: Ovastat;Drug: etoricoxib<br> <br> * Other names: Arcoxia;Drug: pioglitazone<br> <br> * Other names: Actos;Drug: dexamethasone<br> <br> * Other names: Fortecortin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | every 4 weeks up to 24 weeks | 
| 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 | every 4 weeks up to 24 weeks | 
| 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 | every 4 weeks up to 24 weeks | 
| 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. | baseline and Final Visit (week 24) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hormone-refractory, prostate cancer, multitargeted, tyrosinkinase