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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

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An Erratum to this article was published on 10 August 2010

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.

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Acknowledgements

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

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Authors and Affiliations

  1. Duke University, Durham, NS, USA

    Deborah A. Bradley

  2. University of Michigan, Ann Arbor, MI, USA

    Stephanie Daignault, David C. Smith & Maha Hussain

  3. University of California, San Francisco, CA, USA

    Charles J. Ryan & Eric Small

  4. The Cancer Institute of New Jersey, New Brunswick, NJ, USA

    Robert S. DiPaola & Mark N. Stein

  5. Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Mitchell E. Gross

  6. NCI/CTEP, Bethesda, MD, USA

    Alice Chen

  7. University of Michigan Medical Center, 7314 Cancer Center, 1500 East Medical Center Drive, Ann Arbor, MI, 48109-5946, USA

    Maha Hussain

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  1. Deborah A. Bradley
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Correspondence to Maha Hussain.

Additional information

Authors of the DOD Prostate Cancer Clinical Trial Consortium also included Kathleen A. Cooney, Kenneth J. Pienta, MD, Paul Mathew, MD, June Escara-Wilke, MS, Mahmoud Al-Hawary, MD, Evan Keller, DVM, PhD, and Gerald Doyle DDS

This study was presented in part at the 2007 and 2008 American Society of Clinical Oncology Annual Meeting and the 2007 Department of Defense Innovative Minds in Prostate Cancer Treatment (IMPACT 2007) Meeting.

An erratum to this article can be found at http://dx.doi.org/10.1007/s10637-010-9502-7

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Bradley, D.A., Daignault, S., Ryan, C.J. et al. 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. Invest New Drugs 29, 1432–1440 (2011). https://doi.org/10.1007/s10637-010-9420-8

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