A Phase II Study of Ara-C (Cytarabine) in Men With Androgen Independent Prostate Cancer

Study Overview
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Brief Summary
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This is a single-arm, open label phase II trial of the investigational agent, Ara-C (cytarabine), in patients diagnosed with hormone refractory prostate cancer whose disease has progressed on or deemed not suitable for standard chemotherapy with docetaxel. Ara-C appears to inhibit DNA synthesis and is cytotoxic to a wide variety of mammalian cells. Recent discoveries have suggested the role of gene fusions in the ETS family of transcription factors as important for the development of prostate cancer. Ara-C appears to block ETS genes, suggesting that it is worthwhile to explore Ara-C as a potential new treatment for patients with hormone refractory prostate cancer given that there is no standard of care for the proposed patient population. In this study, Ara-C will be administered intravenously for 2 days every 3 weeks (1 cycle). Treatment will be for 6 cycles if tolerated and may be continued in patients who are responding and do not have severe toxicity.

Official Title
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A Phase II Study of Ara-C (Cytarabine) in Men With Androgen Independent Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Cytarabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy-proven prostate cancer or clinical picture consistent with metastatic prostate cancer with high level of serum PSA (> 20ng/ml) At least 4 weeks after docetaxel treatment and have at least 2 consecutive rising PSAs measured at least 2 weeks apart Progression on or intolerance of docetaxel chemotherapy ECOG performance status ≤ 2 Adequate organ and marrow function Exclusion Criteria: Prior treatment with cytarabine Receiving any other investigational or anticancer agents Uncontrolled intercurrent illness Active malignancy at any other site excluding squamous cell or basal cell carcinomas of the skin Radiotherapy within the past 4 weeks

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: Cytarabine<br>eligible patients will receive cytarabine, starting at 075g/m2 and escalating to a maximum of 1.25g/m2, BID IV for 2 days every three weeks for 6 or more cycles if tolerated. | Drug: Cytarabine<br>* Initially given at 1g/m2 bid for 2 days every 3 weeks over 2 hours. The dose will be escalated: level 1 - 1.25g/m2, level 2, 1.5g/m2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PSA response | PSA levels will be collected at screening, baseline, 2 weeks following study termination, and upon followup to determine PSA level response to treatment. | 50% decline in PSA from baseline, confirmed by a second measurement ≥3 weeks later | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain response | Patients will complete Present Pain Intensity (PPI) scale a baseline, every three weeks during treatment and at the end of study. | Baseline median PPI with no concomitant increase in analgesic score/pain | 
| QOL response | Quality of Life (QOL) will be assessed with the Functional Assessment of Cancer Therapy - Prostate questionnaire, self administered by patients. | Baseline to two measurements obtained at least three weeks apart | 
| PSA progression free survival | Time between randomization date and the date of PSA progression (>25% increase from baseline) or the date of death due to prostate cancer, whichever occurs first. | Baseline and the date of PSA progression or the date of death due to prostate cancer, whichever occurs first. | 
| Measurable disease response | Radiological measurement of effect. Measurement at baseline, and every 3 cycles | Every 3 cycles (9 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate, Androgen independent, Phase II, Second line, Androgen-independent prostate cancer