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Clinical Trial
. 2011 Dec;29(6):1432-40.
doi: 10.1007/s10637-010-9420-8. Epub 2010 Mar 25.

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  1 , Stephanie Daignault, Charles J Ryan, Robert S Dipaola, Kathleen A Cooney, David C Smith, Eric Small, Paul Mathew, Mitchell E Gross, Mark N Stein, Alice Chen, Kenneth J Pienta, June Escara-Wilke, Gerald Doyle, Mahmoud Al-Hawary, Evan T Keller, Maha Hussain
Affiliations
Clinical Trial

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 et al. Invest New Drugs. 2011 Dec.

Erratum in

  • Invest New Drugs. 2011 Dec;29(6);1517-8. Cooney, Kathleen A [added]; Mathew, Paul [added]; Pienta, Kenneth J [added]; Escara-Wilke, June [added]; Doyle, Gerald [added]; Al-Hawary, Mahmoud [added]; Keller, Evan T [added]

Abstract

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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Figures

Figure 1
Figure 1. Time to Objective Progression
Progression at 6 months:500mg : 91% (2/22 pts not progressing)
2000mg: 77% (5/22 pts not progressing)
 Median time to progression was 2.7 months (95% CI 2.66, 2.79) on the 500mg arm and .8 months (95% CI 2.66, 5.85) on the 2000mg arm (log-rank p-value=0.52)
Figure 2
Figure 2. Histogram of Circulating Tumor Cells/Circulating Endothelial Cells
See this image and copyright information in PMC

References

    1. EMD 121974 Cilengitide, cyclo-[Arg-Gly-Asp-DPhe-(NMeVal)] Investigator's Brochure
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