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Cixutumumab (IMC-A12)
Cixutumumab, or IMC-A12 is a monoclonal antibody against IGF1-R.
Manufacturer: ImClone, website link www.ImClone.com
oral or intravenous: intravenous
Definition from NCI Drug Dictionary: Cixutumumab is a fully human IgG1 monoclonal antibody directed against the human insulin-like growth factor-1 receptor (IGF-1R) with potential antineoplastic activity. Cixutumumab selectively binds to membrane-bound IGF-1R, thereby preventing the binding of the natural ligand IGF-1 and the subsequent activation of PI3K/AKT signaling pathway. Downregulation of the PI3K/AKT survival pathway may result in the induction of cancer cell apoptosis and may decrease cancer cellular proliferation. IGF-1R, a receptor tyrosine kinase of the insulin receptor superfamily overexpressed by many cancer cell types, stimulates cell proliferation, enables oncogenic transformation, and suppresses apoptosis; IGF-1R signaling has been implicated in tumorigenesis and metastasis.
Development: Evidence from preclinical studies show that Cixutumumab (IMC-A12) effectively blocked IGF-1R and inhibited ligand-dependent signaling and tumor growth in models of human breast cancer, colon and pancreatic cancer. In September 2007, NCI selected 10 proposals for Phase 1 and 2 clinical trials of IMC-A12 exploring the clinical activity, pharmacology and biological effects of the drug as a single agent and in combination with other anti-cancer agents in a wide range of malignancies, including both adult and pediatric sarcomas. Several other proposals have been selected since that time.
Clinical trials with that have relevance to GIST include:
Cixutumumab in Treating Patients With Relapsed or Refractory Solid Tumors
(NCT00831844) Phase II
Temsirolimus and Cixutumumab in Treating Patients With Locally Advanced, Metastatic, or Recurrent Soft Tissue Sarcoma or Bone Sarcoma (NCT01016015) Phase II
Multi-center Phase 1 trial of IMC-A12 in Children with Relapsed/Refractory Solid Tumors (NCT00609141) This trial has been completed.
