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

• Published in: Investigational new drugs Vol. 29; no. 4; p. 674
• Main Authors: Chu, Franklin M, Picus, Joel, Fracasso, Paula M, Dreicer, Robert, Lang, Zhihui, Foster, Brenda
• Format: Journal Article
• Language: English
• Published: United States 01.08.2011
• Subjects: Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - blood; Antibodies, Monoclonal - therapeutic use; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Castration; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Integrin alphaV - immunology; Male; Middle Aged; Neoplasm Metastasis; Prednisone - administration & dosage; Prednisone - therapeutic use; Prostatic Neoplasms - drug therapy; Taxoids - administration & dosage; Taxoids - pharmacology; Taxoids - therapeutic use; Treatment Outcome
• ISSN: 1573-0646
• DOI: 10.1007/s10637-010-9388-4

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). 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. 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.