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A Phase I And Randomized Phase 2 Trial Of Epothilone B Analogue BMS 247550 (NSC # 710428) Administered Every 21 Days With Or Without Oral Estramustine Phosphate In Patients With Androgen Independent Prostate Cancer

Phase 1/Phase 2
18 Years
Not Enrolling
Prostate Cancer

Thank you

Trial Information

A Phase I And Randomized Phase 2 Trial Of Epothilone B Analogue BMS 247550 (NSC # 710428) Administered Every 21 Days With Or Without Oral Estramustine Phosphate In Patients With Androgen Independent Prostate Cancer


- Determine the maximum tolerated dose of ixabepilone combined with estramustine in
patients with progressive androgen-independent adenocarcinoma of the prostate. (Phase

- Compare the safety and efficacy of ixabepilone with or without estramustine in this
patient population. (Phase II)

- Correlate the clinical outcomes with reverse transcriptase-polymerase chain
reaction-based assay for prostate-specific antigen mRNA in patients treated with these

OUTLINE: This is a dose-escalation study of ixabepilone (phase I) followed by a randomized,
multicenter study (phase II).

- Phase I: Patients receive ixabepilone IV over 3 hours on day 2 and oral estramustine 3
times daily on days 1-5. Courses repeat every 3 weeks in the absence of disease
progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of ixabepilone until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2
of 6 patients experience dose-limiting toxicity.

- Phase II: Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive ixabepilone IV over 3 hours at the MTD on day 2 and
estramustine as in phase I.

- Arm II: Patients receive ixabepilone IV over 3 hours at the MTD on day 1.
Treatment in both arms repeats as in phase I.

Patients are followed every 12 weeks until disease progression.

PROJECTED ACCRUAL: A total of 3-12 patients will be accrued for phase I of this study and a
total of 44-92 patients (22-46 per treatment arm) will be accrued for phase II of this study
within 12-18 months.

Inclusion Criteria


- Histologically or cytologically confirmed adenocarcinoma of the prostate

- Must have disease progression meeting 1 of the following criteria:

- Rising prostate-specific antigen (PSA) on at least 3 consecutive measurements
taken more than 1 week apart

- Measurable disease, defined as new or progressive soft tissue masses on CT scan
or MRI

- New metastatic lesions by radionuclide bone scan

- The most recent PSA must be at least 4 ng/mL if no measurable disease is present

- Ineligible if sole manifestation of progressive disease is an increase in
disease-related symptoms

- Serum testosterone no greater than 50 ng/mL

- One of the following therapies for maintenance of castrate status required:

- Must continue on gonadotropin-releasing hormone analogs (e.g., leuprolide or
goserelin) to maintain castrate levels of serum testosterone

- Developed disease progression after discontinuation of the antiandrogen
that was part of the first-line hormonal therapy

- Prior surgical orchiectomy

- Developed disease progression after discontinuation of megestrol

- No known brain metastases



- 18 and over

Performance status:

- Karnofsky 70-100%

Life expectancy:

- Not specified


- WBC at least 3,000/mm^3

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- No history of bleeding disorder that would preclude anticoagulation with warfarin


- Bilirubin normal

- AST/ALT no greater than 2.5 times upper limit of normal (ULN)

- PT/PTT normal (unless anticoagulated for other reasons [e.g., atrial fibrillation])


- Creatinine no greater than 1.5 times ULN


- No significant cardiovascular disease

- No symptomatic congestive heart failure

- No New York Heart Association class III or IV heart disease

- No active unstable angina pectoris

- No cardiac arrhythmia

- No myocardial infarction within the past 6 months

- No history of hemorrhagic or thrombotic cerebrovascular accident or deep venous
thrombosis within the past 6 months


- No pulmonary embolism within the past 6 months


- Fertile patients must use effective contraception

- No history of allergic reactions to compounds of similar chemical or biological
composition to the epothilones

- No history of recent gastrointestinal bleeding that would preclude anticoagulation
with warfarin

- No other concurrent active malignancy except nonmelanomatous skin cancer

- Disease not considered currently active if completely treated with less than a
30% risk for relapse

- No other concurrent uncontrolled illness

- No ongoing or active infection

- No psychiatric illness or social situation that would preclude study compliance


Biologic therapy:

- No concurrent routine filgrastim (G-CSF) or sargramostim (GM-CSF) except for
neutropenic fever

- No concurrent immunotherapy


- No prior chemotherapy

- No other concurrent chemotherapy

Endocrine therapy:

- See Disease Characteristics


- No prior palliative radiotherapy to more than 25% of bone marrow

- No prior radioisotope therapy with strontium chloride Sr 89 or samarium Sm 153
lexidronam pentasodium

- No concurrent therapeutic radiotherapy

- Concurrent focal radiotherapy for palliation of bone disease-related symptoms allowed
at the investigator's discretion


- See Disease Characteristics

- At least 4 weeks since prior major surgery


- No other concurrent anticancer investigational or commercial agents or therapies

- No concurrent herbal, alternative, or food supplements (e.g., PC-SPES, saw palmetto,
or St. John's Wort)

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No initiation of bisphosphonates immediately before or during study

- Concurrent bisphosphonates allowed if developed disease progression while on stable

- Concurrent daily multivitamin allowed

Type of Study:


Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Principal Investigator

Michael Morris, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Federal Government

Study ID:




Start Date:

July 2001

Completion Date:

July 2006

Related Keywords:

  • Prostate Cancer
  • adenocarcinoma of the prostate
  • stage IV prostate cancer
  • recurrent prostate cancer
  • Prostatic Neoplasms



Memorial Sloan-Kettering Cancer Center New York, New York  10021
University of Michigan Comprehensive Cancer Center Ann Arbor, Michigan  48109-0752
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute Boston, Massachusetts  02115
UCSF Comprehensive Cancer Center San Francisco, California  94115