Phase I/II Study of Weekly Intravenous Estramustine Phosphate in Combination With Paclitaxel and Carboplatin in Patients With Advanced Prostate Cancer
OBJECTIVES: I. Determine a safe weekly dose of intravenous estramustine (EM) in combination
with paclitaxel (TAX) and carboplatin (CBDCA) in patients with advanced prostate cancer. II.
Determine the safety and efficacy of this combination in androgen dependent vs androgen
independent disease in these patients. III. Evaluate the pharmacokinetics of weekly
intravenous EM and TAX in combination with CBDCA in these patients.
OUTLINE: Phase I is a dose escalation study of estramustine. Phase II is a two stage design
study, in which patients are stratified according to androgen dependence (androgen dependent
disease vs androgen independent disease). In phase I, patients receive estramustine IV over
1 hour via permanent venous access device on day 1 of weeks 1, 2, 3, and 4, followed by
paclitaxel (TAX) IV over 1 hour. Carboplatin IV is administered over 30 minutes at the
completion of TAX at week 1. Courses repeat every 4 weeks until disease progression or
excessive toxicity or for up to 24 weeks. Patients with locally advanced androgen dependent
prostate cancer may be considered for radical prostatectomy or radiotherapy after 4 courses.
Androgen dependent patients not already on primary hormone therapy with a GnRH analog
receive goserelin or leuprolide injections under the skin every 3 months while on the study,
beginning during the first or second week of therapy. Three patients are entered at each
dose level and must complete one course of therapy. If no patient experiences dose limiting
toxicity (DLT), then 3 patients are treated at the next higher dose level. If 1 patient
experiences DLT, then 3 more patients are treated at that same dose level. If 2 of 6
patients experience DLT, then that dose is declared the maximum tolerated dose (MTD). In
phase II, a two stage design is applied to each patient population. Fourteen patients are
enrolled in the first stage. If no responses are observed, the trial is stopped. If at least
1 response is observed, 11 additional patients will be enrolled onto the study.
PROJECTED ACCRUAL: A total of 6-18 patients will be accrued to phase I; phase II will accrue
up to 50 patients within 3 years.
Primary Purpose: Treatment
William K. Kelly, DO
Memorial Sloan-Kettering Cancer Center
United States: Federal Government
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