Zoledronate and BMS-275291 in Treating Patients With Prostate Cancer

NCT00039104 | Completed Phase 2

• 3 other identifiers: NCI-2012-02799MC0151N01CM17104
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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. 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.

Conditions

Adenocarcinoma of the Prostate; Recurrent Prostate Cancer; Stage IV Prostate Cancer

Outcome Measures

Primary Outcomes (1)

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

  Up to 2 years

Secondary Outcomes (4)

• Overall survival time

  From registration to death due to any cause, assessed for up to 2 years

• Time to disease progression

  From registration to documentation of disease progression, assessed up to 2 years

• Duration of PSA response or duration of PSA control

  Up to 2 years

• Incidence of toxicity as per NCI CTCAE version 2.0

  Up to 2 years

Study Arms (2)

Arm I (rebimastat, zoledronic acid)

EXPERIMENTAL

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

Drug: rebimastat; Drug: zoledronic acid; Other: laboratory biomarker analysis

Arm II (zoledronic acid)

EXPERIMENTAL

Patients receive zoledronate as in Arm I.

Drug: zoledronic acid; Other: laboratory biomarker analysis

Interventions

rebimastat DRUG

Given PO

Also known as: BMS-275291, D2163

Arm I (rebimastat, zoledronic acid)

zoledronic acid DRUG

Given IV

Also known as: CGP 42446, CGP42446A, NDC-zoledronate, zoledronate, Zometa

Arm I (rebimastat, zoledronic acid); Arm II (zoledronic acid)

laboratory biomarker analysis OTHER

Correlative studies

Arm I (rebimastat, zoledronic acid); Arm II (zoledronic acid)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 cancer
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

N-((2S)-2-mercapto-1-oxo-4-(3,4,4- trimethyl-2,5-dioxo-1-imidazolidinyl)butyl)-L-leucyl-N,3- dimethyl-L-Valinamide; Zoledronic Acid

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Roberto Pili

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2002
• First Posted: January 27, 2003
• Study Start: April 1, 2002
• Primary Completion: January 1, 2005
• Last Updated: June 5, 2013

Record last verified: 2013-06

Locations

US (1)