Biomarker Study for Sunitinib and Docetaxel in Prostate Cancer

Study Overview
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Brief Summary
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Docetaxel and sunitinib will be compared to docetaxel for their effect on CEC/CEP spikes induced by docetaxel in HRPC patients

Detailed Description
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Docetaxel (75mg/m2 q21d) is standard of care for patients with hormone refractory prostate cancer (HRPC). Recent data indicate, that chemotherapeutics given at MTD induce, besides their cytotoxic effects, mobilization of circulating endothelial cells (CEC) and - progenitors (CEP) in drug-free breaks of each cycle. In preclinical models, mobilized CEC/CEP result in tumor vasculogenesis and progression of disease. We hypothesize that treatment with sunitinib, an anti-angiogenic tyrosine kinase inhibitor, in between 3 weekly docetaxel disrupts CEC/CEP spikes following docetaxel leading to chemosensitization and reduced tumor re-growth in HRPC patients responding to docetaxel.

Official Title
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Randomized, Controlled Biomarker Study Evaluating the Anti-angiogenic Activity of Sunitinib in Hormone Refractory Prostate Cancer Patients Treated by Docetaxel

Conditions
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Hormone Refractory Prostate Cancer

Intervention / Treatment
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* Drug: Docetaxel * Sunitinib
* Drug: Docetaxel
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: WHO performance status of 0-2. Histologically proven prostate adenocarcinoma. All patients must have prostate adenocarcinoma that is unresponsive or refractory to androgen ablation with biochemical progression Measurable and/or evaluable progressive disease, which is defined by one of the following three criteria: 25% increase in bidimensionally measurable soft tissue metastases Appearance of new metastatic lesions (proven by CT scan, X-ray or bone scan) PSA level of at least 10ng/mL, with increases on at least 2 successive occasions at least 2 weeks apart If the patient has been treated with antiandrogens, treatment must have been stopped at least 6 weeks prior to study randomization Exclusion Criteria: - prior chemotherapy for prostate cancer

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Docetaxel + Sunitinib<br>docetaxel 75mg/m2 day1 q 21d x 4 cycles, sunitinib 37.5mg/d day2 -day15 x 4 cycles | Drug: Docetaxel * Sunitinib<br>* docetaxel 75mg/m2 day1 q 21d x 4 cycles, sunitinib 37.5mg/d day2 -day15 x 4 cycles<br>* Other names: Taxotere + Sutent;|
| Active Comparator: Taxotere<br>docetaxel 75mg/m2 day1 q 21d x 4 cycles | Drug: Docetaxel<br>* docetaxel 75mg/m2 day1 q 21d x 4 cycles<br>* Other names: Taxotere;Drug: Docetaxel<br>* Docetaxel 75mg/m2 q21d for 4 cycles<br>* Other names: Taxotere;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary: CEC/CEP spikes induced by MTD docetaxel in patients treated with docetaxel/sunitinib relative to docetaxel monotherapy |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate and length of treatment holidays relative to docetaxel monotherapy |  | 6 months |