Dataset Information

Cixutumumab, Everolimus, and Octreotide Acetate in Treating Patients With Advanced Low to Intermediate Grade Neuroendocrine Carcinoma

ABSTRACT: This phase I trial studies the side effects and best dose of cixutumumab when given together with everolimus and octreotide acetate in treating patients with advanced low- or intermediate-grade neuroendocrine cancer. Monoclonal antibodies, such as cixutumumab, may find tumor cells and help carry tumor-killing substances to them. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Octreotide acetate may interfere with the growth of tumor cells and slow the growth of neuroendocrine cancer. Giving cixutumumab together with everolimus and octreotide acetate may be a better treatment for neuroendocrine cancer.

DISEASE(S): Neuroendocrine Tumors,Gastrointestinal Neoplasms,Carcinoma,Insulinoma,Pancreatic Insulinoma,Stage Iii Merkel Cell Carcinoma,Stage Iv Merkel Cell Carcinoma,Thyroid Gland Medullary Carcinoma,Carcinoma, Merkel Cell,Regional Digestive System Neuroendocrine Tumor G1,Malignant Carcinoid Syndrome,Lung Carcinoid Tumor,Pancreatic Glucagonoma,Recurrent Pancreatic Neuroendocrine Carcinoma,Metastatic Digestive System Neuroendocrine Tumor G1,Pancreatic Neoplasms,Stomach Neoplasms,Recurrent Merkel Cell Carcinoma,Carcinoid Tumor,Pancreatic Polypeptide Tumor,Paraganglioma,Carcinoma, Medullary,Recurrent Digestive System Neuroendocrine Tumor G1,Gastrinoma,Somatostatinoma,Somatostatin-producing Neuroendocrine Tumor,Carcinoma, Neuroendocrine,Carcinoma, Islet Cell,Glucagonoma,Gastrin-producing Neuroendocrine Tumor,Intestinal Neoplasms

PROVIDER: 2095294 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:The management of neuroendocrine tumors (NETs) is very variable, depending on many specific aspects, such as the type of tumor, spread and patient general health. Several advances have been made with the newly developed somatostatin analogues to cure this type of malignancies. Somatostain analogues such as octreotide have been used in clinic to treat patients with neuroendocrine tumors (NETs). However, the molecular mechanism leading either to successful therapy or acquired resistance to the analogues is still to large extent unclear. Patients develop drugs resistance during a long term treatment. Therefore, to identify the pivotal regulatory genes involved in the development of drug resistance is an actual challenge. We studied five human neuroendocrine tumor cell lines, CNDT2.5, KRJ1, QGP-1, NCI H720 and NCI H727. We also investigated a long-term treated CNDT2.5 by using octreotide. We performed gene expression profiling in all the human neuroendocrine cell lines. Keywords: Gene Expression profiling, treatment comparison We investigated 5 human neuroendocrine cell lines, CNDT2.5 and KRJ1, established from ileum NETs, QGP1 by a pancreatic NET, NCI H720 and NCI H727 from bronchopulmonary NETs. CNDT2.5 cell were constantly treated with 1M-BM-5M octreotide for 10 and 16 months. We isolated total RNA (Ambion, PARISM-bM-^DM-" Kit) from 5 WT cell lines and CNDT2.5 treated with octreotide (Santostatin, Novartis). Total RNA was hybridized onto the Affymetrix Human Gene 1.0 ST Array by Affymetrix Uppsala Platform, UU. SE (Uppsala, Sweden). We first wanted to verify whether the different cell lines may become reliable models to study neuroendocrine signaling pathways. The main objective of this project aimed at understanding the mechanisms by which octrotide (Sandostatin, Novartis) alter cellular growth and differentiation of CNDT2.5 cells. We therefore focused on intermediate (10 months) and long stimulation (16 months) events triggered by sandostatin, which lead variation of CNDT.2.5 cells gene expression to identify potential pivotal genes involved in the development of drug resistance in neuroendocrine cells.

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Cixutumumab, Everolimus, and Octreotide Acetate in Treating Patients With Advanced Low to Intermediate Grade Neuroendocrine Carcinoma

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