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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

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Summary

Background: Integrins mediate invasion and angiogenesis in prostate cancer bone metastases. We conducted a phase II study of Cilengitide, a selective antagonist of αvβ3 and αvβ5 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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Acknowledgement

Cancer Therapy Evaluation Program (CTEP), PC051382, PC051375, Prostate Cancer Foundation (PCF) N008367, Veridex (formerly Immunicon Corp.)

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  1. Ajjai Alva

    Present address: Baylor College of Medicine, Houston, TX, USA

Authors and Affiliations

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

    Ajjai Alva, Stephanie Daignault, Ken Pienta, Kathleen Cooney, David C. Smith & Maha Hussain

  2. Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Susan Slovin

  3. The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Michael Carducci

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

    Robert DiPaola

  5. University of Southern California, Los Angeles, CA, USA

    David Agus

  6. National Cancer Institute, Bethesda, MD, USA

    Alice Chen

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  1. Ajjai Alva
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Correspondence to Maha Hussain.

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This study was presented in part at the 2010 American Society of Clinical Oncology Genitourinary Symposium.

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Alva, A., Slovin, S., Daignault, S. et al. 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. Invest New Drugs 30, 749–757 (2012). https://doi.org/10.1007/s10637-010-9573-5

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