ORIGINAL ARTICLES: Clinical researchA randomized phase II study of cilengitide (EMD 121974) in patients with metastatic melanomaKim, Kevin B.a; Prieto, Victorb; Joseph, Richard W.a; Diwan, Abdul H.b; Gallick, Gary E.c; Papadopoulos, Nicholas E.a; Bedikian, Agop Y.a; Camacho, Luis H.a; Hwu, Patricka; Ng, Chaan S.d; Wei, Weie; Johnson, Marcella M.e; Wittemer, Sabine M.g; Vardeleon, Annaa; Reckeweg, Aarona; Colevas, A. DimitriosfAuthor Information Departments of aMelanoma Medical Oncology bPathology cGenitourinary Medical Oncology dDiagnostic Radiology eBiostatistics, MD Anderson Cancer Center, The University of Texas, Houston, Texas fCancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland, USA gMerck KGaA, Darmstadt, Germany All supplementary digital content is available directly from the corresponding author. Present address: A.H.D.: Baylor College of Medicine, Houston, Texas, USA; L.H.C.: Oncology Consultants, P.A., Houston, Texas, USA; S.M.W.: Bayer Schering Pharma AG, Berlin, Germany; A.D.C.: Stanford University School of Medicine, Stanford, California, USA. Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, 1–5 June 2007, Chicago, IL, USA and at the 45th Annual Meeting of the American Society of Clinical Oncology, 29 May–2 June 2009, Orlando, FL, USA. Correspondence to Kevin B. Kim, MD, Department of Melanoma Medical Oncology, Unit 430, MD Anderson Cancer Center, The University of Texas, 1515 Holcombe Blvd., Houston, TX 77030, USA Tel: +1 713 792 2921; fax: +1 713 745 1046; e-mail: [email protected] Received July 8, 2011 Accepted February 28, 2012 Melanoma Research: August 2012 - Volume 22 - Issue 4 - p 294-301 doi: 10.1097/CMR.0b013e32835312e4 Buy Metrics Abstract Cilengitide (EMD 121974) is a selective inhibitor of integrins αvβ3 and αvβ5. The αvβ3 promotes the proliferation of tumor-associated endothelial cells and potentially the survival of melanoma cells. We conducted a randomized phase II trial in patients with metastatic melanoma to evaluate the clinical efficacy of cilengitide. Patients with stage IV or unresectable stage III melanoma who were either chemonaive or who had previously received one systemic therapy were enrolled. Patients were randomly assigned to either 500 or 2000 mg of cilengitide administered intravenously twice weekly. The primary aim of this study was to determine the progression-free survival rate at 8 weeks. Tumor samples and blood samples were collected for pharmacodynamic and pharmacokinetic studies. Twenty-nine patients were enrolled, of whom 26 were treated (14 at 500 mg and 12 at 2000 mg). Among those treated, only three were progression free at 8 weeks: two in the 500 mg arm and one in the 2000 mg arm. One patient in the 2000 mg arm showed a prolonged partial response after an initial 28% enlargement of her target lesions. The treatment was well tolerated without clinically significant adverse events. The sole responder and one of two patients with stable disease had no αvβ3 expression at baseline. Overall, αvβ3 expression was decreased by day 8 of the treatment (P=0.05). Cilengitide was well tolerated by patients in both the treatment arms but had minimal clinical efficacy as a single-agent therapy for metastatic melanoma, and the efficacy was not related to baseline αvβ3 expression. © 2012 Lippincott Williams & Wilkins, Inc.