A Phase II Study of Docetaxel Plus Carboplatin in Chemonaive Hormone-Refractory Prostate Cancer (HRPC) Patients

Study Overview
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Brief Summary
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The primary objective is to determine the efficacy of docetaxel plus carboplatin as first line treatment in patients with hormone refractory prostate cancer.

Detailed Description
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Docetaxel-prednisolone is the current standard in HRPC, based on 2 large randomized trials showing improved survival compared to mitoxantrone-prednisolone. Carboplatin has activity in prostate cancer and the combination of Docetaxel-carboplatin is known to be synergistic and is used with good effect in many cancers. The advantage of using this combination in prostate cancer is suported by clinical data: high response rates of docetaxel-carboplatin-estramustine (with G-CSF support) in a phase II trial (Oh, Halabi, Kelly et al. Cancer. 2003 Dec 15;98(12):2592-8), and additional effect of this combination in prior taxane failures (Oh, George, Tay. Clin Prostate Cancer. 2005 Jun;4(1):61-4). Carboplatin itself has activity and theoretically could target the more hormone resistant clones or neuroendocrine components of the tumor.(Di Sant' Agnese. J Urol. 1994 Nov;152(5 Pt 2):1927-31.) We are studying the combination of docetaxel-carboplatin both given in a weekly, low-dose fashion, without estramustine and without G-CSF. This is expected to be an effective and tolerable treatment for HRPC patients. We will be documenting (to our knowledge) for the first time in this trial the efficacy of the combination given in this particular dose and schedule.

Official Title
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A Phase II Study of Docetaxel Plus Carboplatin in Chemonaive Hormone-Refractory Prostate Cancer (HRPC) Patients

Conditions
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Hormone-Refractory Prostate Cancer

Intervention / Treatment
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* Drug: Docetaxel, Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed adenocarcinoma of the prostate. At the time of enrollment, patients must have evidence of metastatic disease, with either measurable disease per RECIST criteria or non- measurable disease (i.e. positive bones scan) and PSA > 5 ng/mm3. Disease progression following androgen deprivation therapy. Progression is defined according to the PSA Working Group criteria (see 6.1.3 and 6.3). Serum testosterone levels < 50 ng/mm3 (unless surgically castrate). Patients must continue androgen deprivation with an LHRH analogue if they have not undergone orchiectomy. No use of an antiandrogen for at least 4 weeks. Have not been treated with chemotherapy before. ECOG performance status of <= 2. Laboratory criteria for entry: White blood cell (WBC) => 3000/mm3 Platelets => 100,000/mm3 AST < 2.5 x upper limit of normal Calculated CCT of => 40 ml/min Signed informed consent form. Age: 30 years old and above Exclusion Criteria: Significant peripheral neuropathy defined as grade 2 or higher. Within 4 weeks since completing external beam radiotherapy or 8 weeks since completing radiopharmaceutical therapy (strontium, samarium). Concomitant chemotherapy or investigational agents.

Ages Eligible for Study
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Minimum Age: 30 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: docetaxel and prednisolone<br>Patients in study will receive both chemotherapeutic agents on day 1 and day 8 of every 21-day cycle as described below: Docetaxel 30 mg/m2 over 1 hour IV infusion, followed by Carboplatin (AUC 2) over 1 hour IV infusion Additonal medication required: IV Dexamethasone 10 mg followed by PO dexamethasone 4 mg 8 hourly x 4 doses, starting 12 hours after starting iv docetaxel. | Drug: Docetaxel, Carboplatin<br>* Docetaxel Form: A white, lyophilized powder in vials of 50, 150, and 450 mg each, which should be stored at room temperature in a light-protected area. Carboplatin Form: Taxotere is supplied as a sterile, non-aqueous, viscous solution with an accompanying sterile diluent (13% ethanol in water for injection). 20 and 80 mg strengths are available.<br>* Other names: Docetaxel (Taxotere®);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| efficacy of docetaxel plus carboplatin | The primary endpoint of the study is best overall response (complete or partial response) obtained from measurable target lesion or PSA, as defined using the modified RECIST criteria. | evaluated every 3 cycles (9 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| duration of response and toxicity profile of docetaxel and carboplatin. |  | during patient's treatment |