Phase II Study of the Activity of Weekly Paclitaxel, Topotecan Plus Oral Estramustine Phosphate in Metastatic Hormone-Refractory Prostate Carcinoma
Data Collection
Urogenital Diseases+7
+ Genital Diseases
+ Genital Diseases, Male
Treatment Study
Summary
Study start date: November 1, 2003
Actual date on which the first participant was enrolled.OBJECTIVES: Primary * Determine the objective response rate in patients with metastatic hormone-refractory prostate cancer treated with paclitaxel, topotecan, and estramustine. * Determine the progression-free and overall survival of patients treated with this regimen. * Determine the toxic effects of this regimen in these patients. * Determine the pharmacokinetics of this regimen in these patients. Secondary * Determine the frequency and number of circulating tumor cells in patients before and after treatment with this regimen and at disease progression. * Determine the microtubule morphology, β-tubulin isotype pattern, apoptotic markers, and metaphase chromosome alignment in circulating tumor cells in patients before and after treatment with this regimen and at disease progression. OUTLINE: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15; topotecan IV over 30 minutes on days 2, 9, and 16; and oral estramustine twice daily on days 1 and 2 of course 1 and on days 0-2, 7-9, and 14-16 of all subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. PROJECTED ACCRUAL: A total of 18-38 patients will be accrued for this study.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Male
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
DISEASE CHARACTERISTICS: * Histologically confirmed adenocarcinoma of the prostate gland * Progressive metastatic disease (e.g., bone, pelvic mass, lymph node, liver or lung metastases) * Radiologic evidence of hydronephrosis alone dose not constitute metastatic disease * Failed prior primary hormonal therapy (e.g., estrogen therapy, luteinizing hormone-releasing hormone blocker and flutamide) or bilateral orchiectomy * Patients previously treated with flutamide or bicalutamide must have evidence of disease progression i.e., increasing Prostate-Specific Antigen (PSA) * PSA level ≥ 10 ng/mL if bone metastases only are present (i.e., lacking measurable soft tissue disease) * No elevated serum acid phosphatase or PSA level as the only evidence of disease * No carcinomatous meningitis or brain metastases PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Eastern Cooperative Oncology Group (ECOG) 0-2 Life expectancy * At least 12 weeks Hematopoietic * White Blood Cell (WBC) ≥ 4,000/mm\^3 OR * Granulocyte count ≥ 2,000/mm\^3 * Platelet count ≥ 100,000/mm\^3 Hepatic * Serum Glutamic-Oxaloacetic Transaminase(SGOT) and Serum Glutamic-Pyruvic Transaminase (SGPT) ≤ 2 times normal * Bilirubin ≤ 1.5 mg/dL Renal * Creatinine ≤ 2.0 mg/dL OR * Creatinine clearance ≥ 50 mL/min Cardiovascular * History of deep venous thrombosis allowed provided patients are maintained on therapeutic anticoagulation therapy * No active angina pectoris * No New York Heart Association class II-IV heart disease * No myocardial infarction within the past 6 months * No thrombosis within the past 3 months Other * Fertile patients must use effective contraception during and for 3 months after study participation * No active infection * No other concurrent serious medical illness that would preclude study participation * No other malignancy within the past 3 years except curatively treated basal cell or squamous cell skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * No prior chemotherapy Endocrine therapy * See Disease Characteristics * At least 4 weeks since prior flutamide * At least 8 weeks since prior bicalutamide Radiotherapy * More than 4 weeks since prior radiotherapy * No prior strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium Surgery * See Disease Characteristics Other * Recovered from all prior therapy * No prior cytotoxic therapy for prostate cancer * No concurrent milk, milk products, antacids, calcium-containing drugs, or food during estramustine administration