RATIONALE: Zoledronate may prevent bone loss and stop the growth of tumor cells in bone. BMS-275291 may stop the growth of tumor cells by blocking the enzymes necessary for cancer cell growth. Combining zoledronate with BMS-275291 may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining zoledronate with BMS-275291 in treating patients who have prostate cancer that has not responded to previous hormone therapy.

Condition	Treatment or Intervention	Phase
adenocarcinoma of the prostate stage IV prostate cancer recurrent prostate cancer	Drug: BMS-275291  Drug: zoledronate  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: bone metastases prevention  Procedure: enzyme inhibitor therapy  Procedure: growth factor antagonist therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Compare the confirmed response rate of patients with hormone-refractory prostate cancer treated with zoledronate and BMS-275291.
• Compare the toxicity profile of these regimens in these patients.
• Compare the overall and progression-free survival of patients treated with these regimens.

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. 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.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study within 21 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the prostate
• Refractory to hormonal therapy
• Metastatic bone disease documented by bone scan and confirmed by x-rays, CT scan, or MRI
• Patients may also have measurable disease in retroperitoneal, pelvic, or inguinal lymph nodes or the prostate and/or prostatic bed
• Prostate-specific antigen (PSA) progression
• Two consecutive increases in PSA values
• Measurements taken at least 1 week apart and at least 4 weeks since prior flutamide, nilutamide, or megestrol-based agent (8 weeks for bicalutamide)
• PSA at least 5 ng/mL
• Testosterone less than 50 ng/dL within the past 3 months
• Treatment with one of the following:
• Continuing primary androgen suppression with luteinizing hormone-releasing hormone agonist
• Prior orchiectomy
• No known CNS metastases
• No known visceral metastases (e.g., pulmonary, liver, kidney, or splenic lesions)

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 6 months

Hematopoietic:

• WBC at least 2,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9.0 g/dL

Hepatic:

• Bilirubin no greater than upper limit of normal (ULN)
• AST no greater than 1.5 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other:

• Fertile patients must use effective contraception
• No other prior malignancy except adequately treated basal cell or squamous cell skin cancer, noninvasive carcinoma, or other cancer from which patient has been disease free for at least 5 years
• No other uncontrolled concurrent illness
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No more than 1 prior non-hormonal treatment for metastatic disease, including biologic therapy, gene therapy, and antiangiogenesis therapy
• At least 4 weeks since prior biologic therapy or immunotherapy

Chemotherapy:

• No more than 2 prior chemotherapy regimens

Endocrine therapy:

• See Disease Characteristics
• No concurrent steroids
• No concurrent hormonal agents except luteinizing hormone-releasing hormone

Radiotherapy:

• At least 4 weeks since prior radiotherapy
• No prior systemic radiopharmaceuticals (e.g., samarium Sm 153 lexidronam pentasodium and strontium chloride Sr 89)
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics

Other:

• No other concurrent anticancer agents
• Recovered from all prior therapy
• At least 4 weeks since prior PC-SPES
• Prior bisphosphonates allowed
• No prior matrix metalloproteinase inhibitors
• No other concurrent investigational therapy or supportive care
• No concurrent combination anti-retroviral therapy for HIV-positive patients

Arizona
      Mayo Clinic Scottsdale, Scottsdale,  Arizona,  85259,  United States
Florida
      Mayo Clinic - Jacksonville, Jacksonville,  Florida,  32224,  United States
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231-2410,  United States
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
Missouri
      Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States
Wisconsin
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-6164,  United States

Study chairs or principal investigators

Roberto Pili, MD,  Study Chair,  Sidney Kimmel Cancer Center   

Study ID Numbers:  CDR0000069352; MAYO-MC0151; NCI-5361; NCT00039104
Record last reviewed:  January 2005
Last Updated:  January 12, 2005
Record first received:  June 6, 2002
ClinicalTrials.gov Identifier:  NCT00039104
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08