Title
Docetaxel, Estramustine, and Thalidomide in Treating Patients With Androgen-Independent Metastatic Adenocarcinoma of the Prostate
A Phase II Trial Combining Estramustine, Docetaxel And Thalidomide In Patients With Androgen-Independent Metastatic Prostate Cancer
Phase
Phase 2Lead Sponsor
National Institutes of Health (NIH)Study Type
InterventionalStatus
Completed No Results PostedIndication/Condition
Prostate CancerIntervention/Treatment
thalidomide estramustine docetaxel ...Study Participants
60RATIONALE: Drugs used in chemotherapy, such as docetaxel and estramustine, work in different ways to stop tumor cells from dividing so they stop growing or die. Thalidomide may stop the growth of prostate cancer by stopping blood flow to the tumor. Giving chemotherapy together with thalidomide may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving docetaxel and estramustine together with thalidomide works in treating patients with androgen-independent metastatic adenocarcinoma (cancer) of the prostate.
OBJECTIVES:
Primary
Determine the prostate-specific antigen response in patients with androgen-independent metastatic adenocarcinoma of the prostate treated with docetaxel, estramustine, and thalidomide.
Secondary
Determine the survival duration in patients treated with this regimen.
Determine the pharmacokinetics of both docetaxel and thalidomide in patients treated with this regimen.
Determine whether any pharmacodynamic relationships exist between plasma concentrations of docetaxel and/or thalidomide and clinical activity or toxicity of this regimen in these patients.
Determine the existence of and quantification of circulating prostate cancer cells in patients before and after treatment with this regimen.
Determine genotype, with regard to cytochrome P450 2C19 polymorphism, in patients treated with this regimen.
Correlate genotype with pharmacokinetics and efficacy of this regimen in these patients.
Determine the changes in molecular markers of angiogenesis (including, but not limited to, serum and urine vascular endothelial growth factor) in patients before and after treatment with this regimen.
Determine the toxicity profile of this regimen in these patients.
OUTLINE: This is an open-label study.
Patients receive docetaxel IV over 30 minutes on days 2, 9, and 16, oral thalidomide once daily on days 1-28, and oral estramustine three times daily on days 1-3, 8-10, and 15-17. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Patients are followed for survival.
PROJECTED ACCRUAL: A total of 33-60 patients will be accrued for this study within 11-20 months.
DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the prostate Metastatic disease Androgen-independent disease Clinically progressive disease documented by at least 1 of the following parameters: Two consecutively rising prostate-specific antigen (PSA) levels taken at least 1 week apart PSA ≥ 5.0 ng/mL Continued rise in PSA 4 weeks after discontinuation of prior flutamide OR 6 weeks after discontinuation of prior bicalutamide or nilutamide (for patients treated with anti-androgen agents) At least 1 new lesion on bone scan Progressive measurable disease Must have undergone bilateral surgical castration OR continue on a gonadotropin-releasing hormone agonist No brain metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic Absolute neutrophil count > 1,500/mm^3 Platelet count ≥ 100,000/mm^3* Hemoglobin ≥ 7.5 g/dL* NOTE: *No transfusions within the past 2 weeks Hepatic AST and ALT < 2.5 times upper limit of normal (ULN) Bilirubin < ULN (≤ 3.0 times ULN for patients with Gilbert's syndrome) Alkaline phosphatase ≤ 2.5 times ULN OR Fractionated hepatic alkaline phosphatase ≤ 2.5 times ULN Renal Creatinine ≤ 1.5 mg/dL OR Creatinine clearance ≥ 40 mL/min Cardiovascular No transient ischemic attacks or cerebrovascular accident within the past 2 years No myocardial infarction within the past 6 months No uncontrolled congestive heart failure No uncontrolled angina pectoris No thromboembolic disease Other No peripheral neuropathy ≥ grade 2 No cognitive impairment that would preclude study participation or giving informed consent No other active malignancy within the past 2 years except non-melanoma skin cancer or superficial bladder carcinoma Fertile patients must use effective contraception for at least 1 month before, during, and for at least 1 month after study treatment PRIOR CONCURRENT THERAPY: Biologic therapy No prior thalidomide Chemotherapy No prior docetaxel No prior estramustine No prior chemotherapy for metastatic prostate cancer Endocrine therapy See Disease Characteristics Radiotherapy Recovered from prior radiotherapy Surgery See Disease Characteristics Recovered from prior surgery Other No concurrent antiretroviral therapy for HIV-positive patients No concurrent complementary or alternative therapy that would interact with study drugs No concurrent herbal or nutritional products or dietary supplements that would interact with study drugs No concurrent aprepitant as secondary prophylaxis or antiemetic treatment
