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Phase I/II Study of Weekly Intravenous Estramustine Phosphate in Combination With Paclitaxel and Carboplatin in Patients With Advanced Prostate Cancer

Phase 1/Phase 2
18 Years
Not Enrolling
Prostate Cancer

Thank you

Trial Information

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.

Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically proven prostate cancer that is androgen dependent
or independent Androgen dependent disease must meet ONE OR MORE of the following criteria:
(1) Previously untreated, locally advanced adenocarcinoma of the prostate and: T1-2 tumor
stage, PSA greater than 20 ng/mL OR T3-4 tumor stage OR Gleason grade 8-10 (2) Small cell
carcinoma, poorly differentiated tumor with neuroendocrine features, or neuroendocrine
carcinoma of any stage (3) Disease metastatic to bones or soft tissues (visceral or lymph
nodes) that is evaluable on MRI, CT, or bone scan (patients with evaluable disease that
relapsed after neoadjuvant hormone therapy prior to radical prostatectomy or radiotherapy
are eligible) Patients meeting one of the above criteria who have started on an
antiandrogen (flutamide, nilutamide, or bicalutamide) and/or a gonadotropin releasing
hormone (GnRH) analog (luprolide or goserelin) are eligible if they have been on androgen
ablation (GnRH analog with or without antiandrogen) for no more than 3 months Androgen
independent disease must meet ALL of the following criteria: (1) Disease progression
despite primary hormone treatment (e.g., orchiectomy, estrogen therapy, GnRH analog with
or without an antiandrogen), OR disease progression despite receiving antiandrogen
treatment as part of primary hormone therapy, evidenced by: Bone (new osseous lesion) or
Soft tissue (greater than 25% increase in bidimensionally measurable disease) or Rising
PSA (on any 3 determinations taken at weekly intervals (at least) to greater than 50%
above the patient's baseline PSA value) despite castrate (no greater than 30 ng/mL) levels
of testosterone (2) At least 2 weeks since change in hormone therapy (including prednisone
or dexamethasone) (3) Continuation on treatments to maintain castrate levels of
testosterone if no prior orchiectomy (4) Evaluable or measurable disease (5) No more than
1 prior course of chemotherapy (6) No more than 1 prior course of palliative radiotherapy
or radioisotope treatment (strontium chloride Sr 89)

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 70-100% Life
expectancy: Not specified Hematopoietic: WBC at least 3,000/mm3 Platelet count at least
120,000/mm3 Hemoglobin at least 8.0 g/dL Hepatic: Bilirubin no greater than 1.5 mg/dL or
1.5 times upper limit of normal (ULN) AST no greater than 56 U/L or 1.5 times ULN Renal:
Creatinine no greater than 2.0 mg/dL or 1.5 times ULN Cardiovascular: At least 6 months
since acute deep vein thrombosis and/or pulmonary embolism No serious ventricular
arrhythmia No significant heart disease No active angina (stable or unstable) No
myocardial infarction within 6 months No congestive heart failure No transient ischemic
attack or stroke within 6 months Neurologic: No grade 3-4 peripheral neuropathy Other: No
severe infection No severe malnutrition No other serious medical illnesses

PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since immunotherapy
Chemotherapy: See Disease Characteristics At least 4 weeks since chemotherapy No other
concurrent chemotherapy Endocrine therapy: See Disease Characteristics Radiotherapy: See
Disease Characteristics At least 4 weeks since radiotherapy (8 weeks if systemic
radioisotope treatment with strontium chloride Sr 89) No concurrent radiation of the only
measurable lesion No concurrent radiotherapy or radioisotope therapy Surgery: See Disease
Characteristics At least 4 weeks since major surgery No concurrent surgery to the only
measurable lesion Other: Permanent venous access device (e.g., mediport or Hickman
catheter) required

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

William K. Kelly, DO

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Federal Government

Study ID:




Start Date:

April 1998

Completion Date:

April 2003

Related Keywords:

  • Prostate Cancer
  • adenocarcinoma of the prostate
  • stage I prostate cancer
  • stage IIB prostate cancer
  • stage IIA prostate cancer
  • stage III prostate cancer
  • stage IV prostate cancer
  • recurrent prostate cancer
  • Prostatic Neoplasms



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