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A phase 1, multicenter, open-label study of the safety of two dose levels of a human monoclonal antibody to human αv integrins, intetumumab, in combination with docetaxel and prednisone in patients with castrate-resistant metastatic prostate cancer

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Summary

Purpose We evaluated the safety and efficacy of intetumumab in combination with docetaxel in patients with castrate-resistant metastatic prostate cancer. Patients and methods In this phase 1, open-label, multicenter, nonrandomized study, 75 mg/m2 docetaxel was administered on Day 1 of each of nine 21-day treatment cycles and intetumumab 5 or 10 mg/kg was administered on Days 1, 8, and 15 of Cycles 2 and 3 and on Day 1 of all subsequent cycles. The primary endpoint was the incidence of dose-limiting toxicities (DLTs) during Cycles 2 and 3. Secondary endpoints included serum prostate-specific antigen (PSA) response and objective response based on Response Evaluation Criteria in Solid Tumors (RECIST). Results Ten patients were treated (5 mg/kg n = 3, 10 mg/kg n = 7). No DLTs occurred. Most treatment-emergent adverse events (TEAEs) occurred in the 10-mg/kg intetumumab group. Common TEAEs were neutropenia (10 mg/kg n = 6) and nausea (5 mg/kg n = 1, 10 mg/kg n = 5). Four 10-mg/kg-treated patients reported serious TEAEs; of these, only febrile neutropenia was considered probably intetumumab-related. In the 10-mg/kg group, four patients had a serum PSA response (two of whom responded within 3 months of treatment), one patient demonstrated partial tumor response for 11 weeks, and none had progressive disease at Cycle 9. No PSA or tumor response was observed in the 5-mg/kg group. Conclusions Intetumumab was generally safe and well tolerated in combination with docetaxel, with a higher incidence of TEAEs in the 10 mg/kg dose cohort. The efficacy of 10 mg/kg intetumumab in combination with docetaxel appears to warrant further study.

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Acknowledgments

The authors thank the following investigators and site personnel for their participation in this study: F.M. Chu, D.J. Lama, S. Kim of San Bernardino Urological Associates Medical Group, San Bernardino CA; P.M. Fracasso, J. Picus, P. Hruska, K.A. Bergeron, A.N. Creekmore, S.L. Myles of Siteman Cancer Center at Washington University School of Medicine, St. Louis MO; R. Dreicer, A. Al-Hazzour, S. Black, J. Bray, J. Garcia, T. Filligan, V. Lipnickey, T. Rich, D. Raghavan, B. Rini, I. Tamaskar of The Cleveland Clinic, Cleveland OH.

The authors thank Jennifer Han and Robert Achenbach of Centocor Ortho Biotech Inc. for assistance in drafting, revising, and preparing the manuscript.

Financial support for this study was provided by Centocor, Inc., Malvern, PA.

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Correspondence to Franklin M. Chu.

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Chu, F.M., Picus, J., Fracasso, P.M. et al. A phase 1, multicenter, open-label study of the safety of two dose levels of a human monoclonal antibody to human αv integrins, intetumumab, in combination with docetaxel and prednisone in patients with castrate-resistant metastatic prostate cancer. Invest New Drugs 29, 674–679 (2011). https://doi.org/10.1007/s10637-010-9388-4

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  • DOI: https://doi.org/10.1007/s10637-010-9388-4

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