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Clinical Trial
. 2012 Apr;30(2):749-57.
doi: 10.1007/s10637-010-9573-5. Epub 2010 Nov 4.

Phase II study of cilengitide (EMD 121974, NSC 707544) in patients with non-metastatic castration resistant prostate cancer, NCI-6735. A study by the DOD/PCF prostate cancer clinical trials consortium

Ajjai Alva  1 , Susan Slovin, Stephanie Daignault, Michael Carducci, Robert Dipaola, Ken Pienta, David Agus, Kathleen Cooney, Alice Chen, David C Smith, Maha Hussain
Affiliations
Clinical Trial

Phase II study of cilengitide (EMD 121974, NSC 707544) in patients with non-metastatic castration resistant prostate cancer, NCI-6735. A study by the DOD/PCF prostate cancer clinical trials consortium

Ajjai Alva et al. Invest New Drugs. 2012 Apr.

Abstract

Background: Integrins mediate invasion and angiogenesis in prostate cancer bone metastases. We conducted a phase II study of cilengitide, a selective antagonist of α(v)β(3) and α(v)β(5) integrins, in non-metastatic castration resistant prostate cancer with rising PSA.

Methods: Patients were observed for 4 weeks with PSA monitoring, and then treated with 2,000 mg IV of cilengitide twice weekly until toxicity/progression. PSA, circulating tumor cells (CTCs) and circulating endothelial cells (CECs) were monitored each cycle with imaging performed every three cycles. Primary end point was PSA decline by ≥ 50%. Secondary endpoints were safety, PSA slope, time to progression (TTP), overall survival (OS), CTCs, CECs and gene expression.

Results: 16 pts were enrolled; 13 were eligible with median age 65.5 years, baseline PSA 8.4 ng/mL and median Gleason sum 7. Median of three cycles was administered. Treatment was well tolerated with two grade three toxicities and no grade four toxicities. There were no PSA responses; 11 patients progressed by PSA after three cycles. Median TTP was 1.8 months and median OS has not been reached. Median pre- and on-treatment PSA slopes were 1.1 and 1.8 ng/mL/month. Baseline CTCs were detected in 1/9 patients. CTC increased (0 to 1; 2 pts), remained at 0 (2 pts) or decreased (23 to 0; 1 patient) at progression. Baseline median CEC was 26 (0-61) and at progression, 47 (15-148). Low cell counts precluded gene expression studies.

Conclusions: Cilengitide was well tolerated but had no detectable clinical activity. CTCs are of questionable utility in non-metastatic prostate cancer.

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Figures

Figure 1
Figure 1
Treatment Schema
Figure 2
Figure 2
PSA velocity before and after treatment with Cilengitide in evaluable patients (n=13) The broken and solid lines represent median pre-treatment and post-treatment PSA velocity respectively. Treatment with Cilengitide started at week 0. Individual PSA values for all 13 eligible patients are shown as a scatter plot.
Figure 3
Figure 3
Circulating endothelial cells on treatment (0 weeks indicates start of treatment).
See this image and copyright information in PMC

References

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