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A Phase II, Open-Label, Randomized Trial of Zoledronic Acid (Zometa™) and BMS-275291 (NSC#713763) in Patients With Hormone Refractory Prostate Cancer

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

Thank you

Trial Information

A Phase II, Open-Label, Randomized Trial of Zoledronic Acid (Zometa™) and BMS-275291 (NSC#713763) in Patients With Hormone Refractory Prostate Cancer


I. To evaluate the confirmed response rate of hormone refractory prostate cancer patients
treated with Zometa with BMS-275291.


I. To evaluate the toxicity profile associated with this treatment in this patient

II. To evaluate the overall and progression-free survival associated with this treatment

III. To explore changes markers for bone turnover, fPYR, fDPYR, and serum samples for
cross-linked N-telopeptides from baseline.

IV. To assess changes in bone tumor metabolism after treatment using PET scans. V. To assess
changes in MMP-1, MMP-9, VEGF and bFGF from baseline after treatment.

OUTLINE: This is an open-label, multicenter study. Patients are stratified according to
prior chemotherapy (yes vs no) and participating center.

ARM I: Patients receive zoledronate IV over at least 15 minutes on day 1 and oral BMS-275291
daily on days 1-28.

ARM II (CLOSED TO ACCRUAL AS OF 10/10/2003): Patients receive zoledronate as in Arm I.

In both arms, courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity.

Patients are followed every 3 months until disease progression and then every 6 months for
up to 2 years.

Inclusion Criteria:

- Histologically or cytologically confirmed (adeno)carcinoma of the prostate refractory
to hormone therapy

- Metastatic bone disease, as documented by bone scan and confirmed by x-rays, CT scan
or MRI scan

- Note: Patients may also have measurable disease in the lymph nodes
(retroperitoneal, pelvic or inguinal only), prostate and /or prostatic bed;
measurable disease is defined as lesions that can be accurately measured in at
least one dimension (longest diameter to be recorded) as >= 20 mm =< 21 days
prior to registration

- PSA progression defined as two consecutive increases in PSA value over the previous
reference value; the first increase of PSA should occur no earlier than one (1) week
after the reference measurement; all patients need to demonstrate continued PSA
elevation with an increasing PSA four weeks after the required cessation of their
antiandrogen treatment; the required cessation period is 4 weeks for flutamide,
nilutamide, and Megace-based treatment, and 8 weeks for bicalutamide-based treatment

- One of the following:

- Continuing primary androgen suppression (LHRH agonist)

- Orchiectomy

- WBC >= 2000/mm^3

- Absolute neutrophil count (ANC) >= 1500/mm^3

- PLT >= 100,000/mm^3

- Hgb >= 9.0 g/dL

- Total bilirubin =< institutional upper normal limits (UNL)

- AST =< 1.5 x UNL

- Serum creatinine =< 1.5 x UNL

- PSA >= 5 ng/mL

- Serum testosterone < 50 ng/dL =< 3 months prior to registration

- Estimated life expectancy of >= 6 months

- ECOG Performance Status (PS) 0, 1, or 2

- Capable of understanding the investigational nature, potential risks and benefits of
the study and able to provide valid informed consent

- If sexually active, willing to use an accepted and effective method of contraception
consistently for the duration of study participation

Exclusion Criteria:

- Any of the following:

- > 2 prior chemotherapy regimen

- > 2 non-hormonal treatments for metastatic disease (including biologics, gene
therapy, angiogenesis inhibitors, etc., but excluding external radiotherapy)

- Prior therapy with a matrix metalloproteinase inhibitor (MMPI)

- Immunotherapy =< 4 weeks prior to study entry

- Biologic therapy =< 4 weeks prior to study entry

- Radiation therapy =< 4 weeks prior to study entry

- Concomitant hormonal treatment (except LHRH)

- Prior use of systemic radiopharmaceuticals such as samarium and strontium

- PC-Spes =< 4 weeks prior to study entry

- Failure to fully recover from adverse effects of prior therapies regardless of
interval since last treatment

- Other concurrent chemotherapy, immunotherapy, or radiotherapy directed at the

- Other therapy or supportive care that is considered investigational

- Known CNS metastases

- Known visceral metastases (pulmonary, liver, kidney, splenic lesions); patients with
retroperitoneal, pelvic or inguinal lymph node metastases and/or disease in the
prostate (or prostatic bed) will not be excluded

- Uncontrolled intercurrent illness including, but not limited to:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris, cardiac arrhythmia

- Psychiatric illness/social situations that would limit compliance with study

- HIV-positive patients receiving combination anti-retroviral therapy

- Prior malignancy except for adequately treated basal cell or squamous cell skin
cancer, adequately treated noninvasive carcinomas, or other cancer from which the
patient has been disease free for >= 5 years

Type of Study:


Study Design:

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

Outcome Measure:

Confirmed response (PSA decline of greater than 50% confirmed at least four weeks apart)

Outcome Time Frame:

Up to 2 years

Safety Issue:


Principal Investigator

Roberto Pili

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

April 2002

Completion Date:

Related Keywords:

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



Mayo Clinic Rochester, Minnesota  55905