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Phase II study of cixutumumab (IMC-A12) plus depot octreotide for patients with metastatic carcinoid or islet cell carcinoma.
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2010
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ImmunologyIslet Cell CarcinomaPathologyPhase Ii StudyImmunoeditingImmunotherapyTumor BiologyOncologySomatostatin Analogue OctreotideRadiation OncologyCancer ResearchMolecular OncologyTps220 BackgroundDepot OctreotideTumor GrowthCancer TreatmentMalignant DiseaseTumor MicroenvironmentImmune Checkpoint InhibitorMedicineCancer Growth
TPS220 Background: The somatostatin analogue octreotide is an established therapy offering symptom relief in patients with neuroendocrine tumors; however, their prognosis remains limited. Cixutumumab, a fully human IgG1 monoclonal antibody, specifically targets insulin-like growth factor receptor I (IGF-IR) with high affinity and antagonizes IGF-I and IGF-II ligand binding and signaling. It inhibits the IGF-IR pathway by effecting internalization and degradation of IGF-IR, leading to a reduction in surface receptors. In vitro and in vivo, cixutumumab inhibits proliferation of a variety of human tumor cell lines (Cancer Res. 2003;63:8912; Clin Cancer Res. 2005;11:3065). A significant proportion of neuroendocrine tumors express IGF and/or the IGF-IR and the binding of IGF-I to its receptor appears to promote cell growth. High levels of IGF-IR expression have been associated with faster tumor growth, increased aggressiveness, and lower likelihood of cure in one NET subtype (gastrinoma). (Clin Cancer Res. 2005;11;9:3233). IGF-IR inhibition effects a reduction in IGF-stimulated IGF-IR phosphorylation, promoted apoptosis, and inhibits the growth of tumor cells in vitro and in vivo. Methods: Adult subjects currently receiving depot octreotide therapy for metastatic neuroendocrine carcinomas of carcinoid (30 patients) or islet cell (30 patients) histology that have progressed on prior therapy will be enrolled. Tumors must have Ki-67 expression ≤ 20%. Safety and efficacy will be evaluated with 6-month progression-free survival as the primary variable. Possible reduction in tumor-specific markers and the effect of combination therapy on selected pharmodynamic markers will be assessed. Patients will receive cixutumumab (10 mg/kg i.v.) every 2 weeks and will continue to receive the same dose and schedule of their last regimen of depot octreotide until disease progression or other reasons for study termination. Results: As of January 12, 2010, 27 patients have been enrolled at 7 study sites in the United States. Conclusions: This Phase II study is currently accruing at the expected rate. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ImClone Systems ImClone Systems