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A Randomized Phase II Study Of BMS 247550 Or Mitoxantrone And Prednisone In Patients With Taxane Resistant Hormone Refractory Prostate Cancer

Phase 2
18 Years
Not Enrolling
Adenocarcinoma of the Prostate, Recurrent Prostate Cancer, Stage IV Prostate Cancer

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Trial Information

A Randomized Phase II Study Of BMS 247550 Or Mitoxantrone And Prednisone In Patients With Taxane Resistant Hormone Refractory Prostate Cancer


I. Determine the efficacy of ixabepilone (BMS-247550) vs mitoxantrone and prednisone, in
terms of decline in prostate-specific antigen (PSA) levels, in patients with
taxane-resistant, hormone-refractory metastatic prostate cancer.


I. Determine the safety of these regimens in these patients. II. Determine the objective
response rate in patients with measurable disease who are treated with these regimens.

III. Determine the clinical activity of each of these regimens after crossover in patients
who experience disease progression on their originally assigned treatment arm and switch to
the other treatment arm.

OUTLINE: This is a randomized, crossover, multicenter study. Patients are stratified
according to ECOG performance status (0 vs 1 or 2). Patients are randomized to 1 of 2
treatment arms.

ARM I: Patients receive ixabepilone (BMS-247550) IV over 3 hours on day 1.

ARM II: Patients receive mitoxantrone IV over 30 minutes on day 1 and oral prednisone twice
daily on days 1-21.In both arms, courses repeat every 21 days in the absence of disease
progression or unacceptable toxicity.

Patients who progress while on treatment after at least 2 courses or discontinue treatment
for any other reason may cross over to the other arm and receive treatment as above,
beginning within 12 weeks of last study treatment on original arm.

Patients are followed every 3 months.

Inclusion Criteria:

- Histologically confirmed adenocarcinoma of the prostate

- Metastatic disease (positive bone scan or measurable disease)

- Progressive hormone-refractory disease

- Based on 1 of the following:

- Transaxial imaging

- Rise in prostate-specific antigen (PSA)

- Radionuclide bone scan

- Must have undergone primary hormonal treatment (e.g., orchiectomy or
gonadotropin-releasing hormone analog with or without an antiandrogen) and
demonstrated disease progression after antiandrogen discontinuation as defined

- Two consecutive rising PSA values, obtained at least 2 weeks apart, or
documented osseous or soft tissue progression

- For patients receiving flutamide, at least 1 PSA value must be obtained at
least 4 weeks after flutamide discontinuation

- For patients receiving bicalutamide or nilutamide, at least 1 PSA value
must be obtained at least 6 weeks after antiandrogen discontinuation

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

- Meets 1 of the following criteria:

- Measurable disease and an elevated PSA

- Nonmeasurable disease and an elevated PSA, as follows:

- Positive bone scan

- PSA level at least 5 ng/mL, with increases on at least 2 successive
occasions at least 2 weeks apart

- New metastatic lesions by radionuclide bone scan

- Must have received at least 2 courses of paclitaxel- or docetaxel-based therapy, with
disease progression documented during therapy or no more than 60 days after cessation
of therapy*

- Testosterone < 50 ng/dL

- No known active brain metastases

- Performance status - ECOG 0-2

- At least 12 weeks

- Granulocyte count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Bilirubin < 1.5 times upper limit of normal (ULN)

- AST and ALT < 3 times ULN

- Creatinine ≤ 1.5 times ULN

- Creatinine clearance > 40 mL/min

- Ejection fraction ≥ lower limit of normal by MUGA or echocardiogram

- No myocardial infarction within the past 6 months

- No significant cardiovascular disease

- No New York Heart Association class III or IV congestive heart failure

- No active angina pectoris

- Fertile patients must use effective contraception before, during, and for 3 months
after study therapy

- No prior hypersensitivity reaction to agents containing Cremophor®EL

- No serious infection

- No nonmalignant medical illnesses that are uncontrolled or whose control would be
jeopardized by complications of study therapy

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

- No motor or sensory neuropathy grade 2 or greater

- No "currently active" second malignancy except nonmelanoma skin cancer

- Patients are not considered to have a "currently active" malignancy provided
they have completed therapy and are considered to have less than a 30% risk of

- No concurrent prophylactic colony-stimulating factors for myelosuppression

- See Disease Characteristics

- No more than 1 prior chemotherapy regimen

- No prior mitoxantrone or epothilone

- No other concurrent chemotherapy

- See Disease Characteristics

- At least 4 weeks since prior antiandrogens (e.g., flutamide) (6 weeks for
bicalutamide or nilutamide)

- Patients must continue primary androgen deprivation therapy with luteinizing
hormone-releasing hormone agonist during study if prior orchiectomy was not

- At least 4 weeks since prior systemic (including oral) corticosteroids except
corticosteroids as part of first-line chemotherapy tapered off over 10-14 days prior
to study entry

- At least 4 weeks since any prior hormonal therapy, including megestrol or finasteride

- No other concurrent systemic steroids

- At least 4 weeks since prior radiotherapy

- More than 8 weeks since prior radiopharmaceuticals (e.g., strontium chloride Sr 89 or
samarium Sm 153 lexidronam pentasodium)

- No concurrent radiotherapy

- See Disease Characteristics

- At least 4 weeks since prior herbal products known to decrease PSA levels (e.g., Saw
Palmetto or PC-SPES)

- More than 4 weeks since other prior antiprostate cancer therapy

- More than 4 weeks since prior systemic therapies for prostate cancer

- No other concurrent investigational agents

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response to the randomized treatment as determined by > 50% PSA response as measured by RECIST criteria

Outcome Description:

The frequency of response with 95% confidence limits for a binomial outcome will be calculated.

Outcome Time Frame:

Up to 3 months

Safety Issue:


Principal Investigator

Jonathan Rosenberg

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of California, San Francisco


United States: Food and Drug Administration

Study ID:




Start Date:

March 2003

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Prostate
  • Recurrent Prostate Cancer
  • Stage IV Prostate Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Prostatic Neoplasms



UCSF Helen Diller Family Comprehensive Cancer Center San Francisco, California  94115