Docetaxel, Estramustine, and Exisulind in Treating Patients With Metastatic Prostate Cancer That Has Not Responded to Hormone Therapy

Study Overview
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Brief Summary
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RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Estramustine may fight prostate cancer by reducing the production of androgens. Exisulind may stop the growth of prostate cancer by stopping blood flow to the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining these therapies may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining estramustine with exisulind and docetaxel in treating patients who have metastatic prostate cancer that has not responded to hormone therapy.

Detailed Description
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OBJECTIVES: Determine the time to objective and biochemical progression and response proportion (objective and post-therapy changes in PSA) in patients with hormone refractory metastatic prostate cancer treated with docetaxel, estramustine, and exisulind. Determine the toxic effects of this regimen in these patients. Determine the overall survival of patients treated with this regimen. OUTLINE: Patients receive oral estramustine 3 times daily on days 1-5, docetaxel IV over 1 hour on day 2, and oral exisulind twice daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years.

Official Title
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A Phase II Study Of Estramustine, Docetaxel, And Exisulind (IND #64733) In Men With Hormone Refractory Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: docetaxel
* Drug: estramustine phosphate sodium
* Drug: exisulind


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the prostate Progressive systemic (metastatic) disease despite castrate levels of testosterone secondary to orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist therapy Castrate levels of testosterone must be maintained LHRH analog therapy should be continued Failed prior standard androgen-deprivation therapy Serum testosterone no greater than 50 ng/mL for patients who have not had bilateral orchiectomy Evidence of metastatic disease on CT scan, MRI, or bone scan (no positron-emission tomography or prostascint) Evidence of progressive disease after most recent prior therapy (including hormonal therapy) as defined by 1 of the following: Measurable disease progression More than 20% increase in the sum of the longest diameters of target lesions from the time of maximal regression or the appearance of 1 or more new lesions Bone scan progression Appearance of 1 or more new lesions on bone scan attributable to prostate cancer AND PSA at least 5 ng/mL PSA progression PSA at least 5 ng/mL which has increased serially from baseline on 2 occasions (at least 1 week apart) NOTE: If the confirmatory PSA is less than screening PSA, an additional test for rising PSA is required PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic Granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic AST and ALT no greater than 1.5 times upper limit of normal (ULN) Bilirubin no greater than ULN Renal Creatinine no greater than 1.5 times ULN Cardiovascular No myocardial infarction within the past year No significant change in anginal pattern within the past year No congestive heart failure No New York Heart Association class II-IV heart disease No deep vein thrombosis within the past year Pulmonary No pulmonary embolus within the past year Other No clinically significant peripheral neuropathy No known hypersensitivity to sulindac Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior cytotoxic chemotherapy (including estramustine or suramin) No other concurrent chemotherapy Endocrine therapy See Disease Characteristics At least 4 weeks since prior flutamide and megestrol At least 6 weeks since prior bicalutamide and nilutamide At least 4 weeks since prior hormonal therapy known to decrease PSA levels (including ketoconazole, aminoglutethimide, finasteride, or any systemic corticosteroid) Concurrent primary testicular androgen suppression therapy (e.g., with a LHRH analog) allowed No other concurrent hormonal therapy except: Steroids for adrenal insufficiency Hormones for non-disease-related conditions (e.g., insulin for diabetes) Intermittent dexamethasone as an antiemetic Radiotherapy At least 4 weeks since prior radiotherapy and recovered At least 8 weeks since prior strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium No concurrent palliative radiotherapy Surgery See Disease Characteristics At least 4 weeks since prior major surgery and recovered Other At least 4 weeks since prior herbal product known to decrease PSA levels (including saw palmetto, PC-SPES) More than 1 week since prior sulindac No concurrent sulindac No concurrent chronic nonsteroidal anti-inflammatory drugs (including COX-2 inhibitors and salicylates such as aspirin, mesalamine, salsalate, and sulfasalazine) Concurrent ibuprofen and naproxen allowed Low-dose aspirin (e.g., 81 mg/day) for cardiovascular prevention allowed No concurrent full-dose oral or parenteral anticoagulation therapy Concurrent bisphosphonate therapy allowed provided therapy was initiated at least 4 weeks before study and disease has progressed despite therapy

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combined chemotherapy<br>combination of 3 chemotherapy agents for hormone refractory prostate cancer | Drug: docetaxel<br>* 70 mg/sq m IV infusion over 1 hour Day 2 of ea cycle<br>Drug: estramustine phosphate sodium<br>* 280 mg PO tid Days 1-5 of ea cycle<br>Drug: exisulind<br>* Two 125 mg capsules PO bid Days 1-21 of ea cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression |  | 24 months from study entry | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity |  | treatment up to 3 mon post treatment | 
| Changes in PSA |  | During treatment then q 3 mon until ds progression | 
| Overall Survival |  | 24 months from study entry | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the prostate, recurrent prostate cancer, stage IV prostate cancer