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Investigational New Drugs

, Volume 29, Issue 6, pp 1432–1440 | Cite as

Cilengitide (EMD 121974, NSC 707544) in asymptomatic metastatic castration resistant prostate cancer patients: a randomized phase II trial by the prostate cancer clinical trials consortium

  • Deborah A. Bradley
  • Stephanie Daignault
  • Charles J. Ryan
  • Robert S. DiPaola
  • David C. Smith
  • Eric Small
  • Mitchell E. Gross
  • Mark N. Stein
  • Alice Chen
  • Maha HussainEmail author
PHASE II STUDIES

Summary

Background Integrins are involved in prostate cancer metastasis by regulating cell adhesion, migration, invasion, motility, angiogenesis and bone metabolism. We evaluated the efficacy of two dose levels of cilengitide in patients (pts) with castrate resistant prostate cancer (CRPC). Methods Chemotherapy-naïve, asymptomatic metastatic CRPC pts were randomized to cilengitide 500 mg or 2,000 mg IV twice weekly using parallel 2-stage design. The primary endpoint was rate of objective clinical progression at 6-months. Secondary endpoints included clinical and PSA response rates, safety and effects of cilengitide treatment on circulating tumor cells (CTCs) and bone remodeling markers. Results Forty-four pts were accrued to first stage (22/arm). Median number of cycles was three in both arms (500 mg arm: 1–8; 2,000 mg arm: 1–15). At 6 months, two pts (9%) on the 500 mg arm and five pts (23%) on the 2,000 mg arm had not progressed. Best objective response was stable disease (SD) in seven pts for 9.9[8.1,20.9] months. There were three grade 3 and no grade 4 toxicities. At 12 weeks, analysis of bone markers did not reveal significant trends. At progression, bone specific alkaline phosphatase and N-telopeptide increased in all pts, less so in pts on the 2,000 mg arm and in pts on both arms who obtained SD at 6 months. CTCs increased over time in both arms. Conclusion Cilengitide was well tolerated with modest clinical effect in favor of the higher dose. The unique trial design including a shift from response rate to objective progression as the endpoint, and not acting on PSA increases was feasible.

Keywords

Prostate cancer Metastatic disease Integrins Angiogenesis Cilengitide Bone biomarkers 

Notes

Acknowledgements

CTEP, Prostate SPORE Grant P50 CA069568-09, Merck KGaA, PC051382, PC051375, PCF N008367, Immunicon Corporation.

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Deborah A. Bradley
    • 1
  • Stephanie Daignault
    • 2
  • Charles J. Ryan
    • 3
  • Robert S. DiPaola
    • 4
  • David C. Smith
    • 2
  • Eric Small
    • 3
  • Mitchell E. Gross
    • 5
  • Mark N. Stein
    • 4
  • Alice Chen
    • 6
  • Maha Hussain
    • 2
    • 7
    Email author
  1. 1.Duke UniversityDurhamUSA
  2. 2.University of MichiganAnn ArborUSA
  3. 3.University of CaliforniaSan FranciscoUSA
  4. 4.The Cancer Institute of New JerseyNew BrunswickUSA
  5. 5.Cedars-Sinai Medical CenterLos AngelesUSA
  6. 6.NCI/CTEPBethesdaUSA
  7. 7.University of Michigan Medical CenterAnn ArborUSA

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