Official Title: “Phase II Trial Of Sequential Estramustine/Paclitaxel Followed By Doxorubicin/Ketoconazole In Patients With Androgen-Independent Prostate Cancer”

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.

Study Type: Interventional

Study Design: Treatment

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.

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.

Intervention(s) in this Clinical Trial

• Drug: docetaxel
• Drug: doxorubicin hydrochloride
• Drug: estramustine phosphate sodium
• Drug: ketoconazole
• Drug: warfarin

• 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
• 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
• 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

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Memorial Sloan-Kettering Cancer Center

Overall Clinical Trial Officials and Contacts

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

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00014352

Study ID Number: CDR0000068536

ClinicalTrials.gov Identifier: NCT00014352

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database