RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Anticoagulant drugs such as warfarin may reduce the risk of blood clots. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy plus warfarin in treating patients who have prostate cancer.

Condition	Treatment or Intervention	Phase
stage III prostate cancer stage IV prostate cancer Thromboembolism recurrent prostate cancer	Procedure: supportive care  Procedure: chemotherapy  Behavior: supportive care/therapy  Procedure: thrombolytic therapy  Drug: docetaxel  Drug: doxorubicin  Drug: estramustine  Drug: ketoconazole  Drug: warfarin	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the safety, efficacy, and durability of docetaxel and estramustine followed by doxorubicin and ketoconazole in patients with high-risk, androgen-independent prostate cancer. II. Determine whether anticoagulation with warfarin can reduce the frequency of thromboembolic complications associated with estramustine in these patients.

PROTOCOL OUTLINE: Regimen A: Patients receive oral estramustine 3 times daily on days 1-5 and docetaxel IV over 1 hour on day 3 weekly. Patients also receive oral warfarin daily. Treatment repeats every 4 weeks for a total of 2 courses in the absence of disease progression or unacceptable toxicity. Regimen B: After completion of regimen A, patients receive doxorubicin IV over 30 minutes weekly and oral ketoconazole twice daily. Treatment repeats every 4 weeks for a total of 2 courses in the absence of disease progression or unacceptable toxicity. Patients are followed monthly until disease progression.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study within 1 year.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed prostate cancer
• High risk as defined by any 2 of the following: Karnofsky performance status of 70-80%; Lactate dehydrogenase greater than 200 U/mL; Hemoglobin less than 13 g/dL
• Prostate-specific antigen (PSA) at least 4 ng/mL
• Progressive disease based on any 1 of the following: Rise in PSA level of at least 25% above baseline; At least 3 determinations taken at weekly intervals OR At least 2 determinations taken at monthly intervals; New or progressive soft tissue masses on MRI or CT scan; Radionucleotide bone scan with new metastatic lesion(s)
• Serum testosterone no greater than 30 ng/mL
• If no prior surgical orchiectomy, castrate levels of serum testosterone must be maintained with continuation of gonadotropin releasing hormone analogs
• If receiving an anti-androgen, must show progression of disease after stopping anti-androgen therapy

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No more than 1 prior chemotherapy regimen
• Endocrine therapy: See Disease Characteristics
• Radiotherapy: No more than 1 prior course of palliative radiotherapy; No more than 1 prior radioisotope therapy with strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium
• Surgery: See Disease Characteristics; At least 4 weeks since prior major surgery

--Patient Characteristics--

• Age: 18 and over
• Performance status: See Disease Characteristics; Karnofsky 70-100%
• Life expectancy: Not specified
• Hematopoietic: See Disease Characteristics; WBC at least 3,000/mm3; Platelet count at least 100,000/mm3
• Hepatic: Bilirubin normal; SGOT/SGPT no greater than 1.5 times upper limit of normal (ULN)
• Renal: Creatinine no greater than 1.5 times ULN
• Cardiovascular: No significant cardiovascular disease; No New York Heart Association class III or IV heart disease; No active angina pectoris; No myocardial infarction within the last 6 months; Ejection fraction at least 45% by echocardiogram or MUGA; No prior hemorrhagic or thrombotic cerebral vascular accident; No deep venous thrombosis
• Pulmonary: No pulmonary embolism within the past 6 months
• Other: No history of bleeding disorder or gastrointestinal bleeding that would preclude anticoagulation with warfarin; No other concurrent malignancy except non-melanoma skin cancer or any curatively treated malignancy considered to be at less than 30% risk of relapse; No severe infection; No severe malnutrition; No other serious medical illness that would preclude study

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States

Study chairs or principal investigators

William K. Kelly,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000068536; MSKCC-00113; NCI-G01-1927
Record last reviewed:  November 2003
Last Updated:  October 13, 2004
Record first received:  April 10, 2001
ClinicalTrials.gov Identifier:  NCT00014352
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08