Docetaxel Plus Estramustine in Treating Patients With Metastatic Prostate Cancer

PHASE I/II STUDY OF DOCETAXEL (TAXOTERE) AND ESTRAMUSTINE COMBINATION CHEMOTHERAPY IN PATIENTS WITH 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.

PURPOSE: Phase I/II trial to study the effectiveness of combining docetaxel and estramustine in treating patients who have metastatic prostate cancer.

Study Overview

• Status: Unknown
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: docetaxel; Drug: estramustine phosphate sodium

Detailed Description

OBJECTIVES: I. Determine the maximum tolerated dose, toxicity, and pharmacokinetic profile of docetaxel in combination with estramustine in patients with metastatic adenocarcinoma of the prostate. II. Determine the safe dose level of this regimen for Phase II evaluation. III. Determine the efficacy of this regimen with evaluation of objective response rate, duration of response, and time to disease progression in these patients. IV. Determine the duration of survival of these patients on this regimen. V. Evaluate the symptomatic and quality of life effects in these patients.

OUTLINE: This is a dose escalation study (phase I). Patients are stratified into one of two risk groups by number of prior chemotherapy regimens (0-2 vs greater than 2) and occurrence and site(s) of prior radiation. Patients receive oral estramustine three times daily beginning 24 hours prior to docetaxel and continuing for 4 days after infusion. Patients receive docetaxel IV over 1 hour every 21 days. Cohorts of 3-6 patients receive escalating doses of docetaxel until the maximum tolerated dose (MTD) is reached (phase I). The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicity. A minimum of 6 patients receive treatment at the MTD. Phase II: Patients receive docetaxel IV at the MTD from phase I. Treatment continues in the absence of disease progression or unacceptable toxicity for both phases. Quality of life is assessed. Patients are followed every 3 months until death.

PROJECTED ACCRUAL: Approximately 12-37 patients will be accrued for this study within 13-19 months.

• Study Type: Interventional
• Enrollment (Anticipated): 37
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Herbert Irving Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

DISEASE CHARACTERISTICS: Histologically confirmed metastatic adenocarcinoma of the prostate Failure of androgen ablation (orchiectomy or luteinizing hormone releasing hormone, flutamide) -Rise in PSA greater than 50% of nadir confirmed by 2 measurements 1 week apart -Appearance of new soft tissue lesions -Appearance of new lesions on bone scan Measurable or evaluable disease No symptomatic ascites, pleural effusions, or peripheral edema greater than trace No brain or leptomeningeal involvement

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: WBC at least 3,500/mm3 Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 No history of coagulopathy Hepatic: Bilirubin no greater than upper limit of normal (ULN) SGOT or SGPT no greater than 2.0 times ULN Alkaline phosphatase no greater than 5.0 times ULN Renal: Creatinine no greater than 2.0 times ULN Cardiovascular: No myocardial infarction within past 6 months Pulmonary: No prior pulmonary embolus Neurologic: No prior cerebrovascular accident No symptomatic peripheral neuropathy greater than grade 1 No significant neurologic or psychiatric disorder (psychotic disorder, dementia, or seizure) Other: No other prior malignancy within past 5 years, except: Excised or curatively irradiated nonmelanomatous skin cancer No other serious illness or medical condition No active infection

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 4 weeks since prior chemotherapy Endocrine therapy: At least 4 weeks since prior hormonal therapy Radiotherapy: At least 4 weeks since prior radiotherapy At least 6 weeks since prior isotope therapy No prior radiotherapy to greater than 30% of bone marrow Surgery: Not specified Other: At least 4 weeks since prior investigational drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Herbert Irving Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: February 1, 1998

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: September 1, 2004
• First Posted (Estimate): September 2, 2004

Study Record Updates

• Last Update Posted (Estimate): January 6, 2014
• Last Update Submitted That Met QC Criteria: January 3, 2014
• Last Verified: April 1, 2000

More Information

Terms related to this study

• Keywords: stage IV prostate cancer; recurrent prostate cancer; adenocarcinoma of the prostate
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Docetaxel; Estramustine
• Other Study ID Numbers: CDR0000064755; CPMC-IRB-7386; NCI-V96-0888