The Cancer Therapy Evaluation Program (CTEP) is accepting Letters of Intent (LOIs) to conduct clinical studies using Lutathera®, a radiolabeled somatostatin analog, which is being developed by CTEP as an anticancer agent in collaboration with Advanced Accelerator Applications (AAA) - Novartis Pharmaceutical Company. CTEP will also consider requests to supply Lutathera® for nonclinical studies. All clinical and nonclinical researchers possessing an interest in working with the agent are welcome to apply. Proposals for clinical trials should be supported by a strong rationale and robust preclinical data (see “Components of a Competitive Letter of Intent” at http://ctep.cancer.gov/protocolDevelopment/lois_concepts.htm). All proposals approved by CTEP will be sent to the industry collaborator for a commitment to supply drug for the study.
Lutathera®, lutetium-177 ( 177Lu)-dotatate, is a beta-emitting radionuclide that can deliver a tumoricidal radiation dose to tissues overexpressing somatostatin-receptors (SSTRs). The antitumor activity of somatostatin occurs directly via cell cycle arrest and/or apoptosis downstream from tumor SSTR activation, and indirectly via SSTR-induced inhibition of tumor angiogenesis and the production of factors that support tumor growth. 177Lu induces cellular damage by formation of free radicals in SSTR-positive cells and in neighboring cells. In rat SSTR-positive tumor models, Lutathera® treatment resulted in complete ablation of implanted tumors (Erlion et al., 2000), while half of the SSTR-positive rats treated with Lutathera® lived a normal life span without tumor recurrence. On January 26, 2018, the FDA approved Lutathera® for the treatment of SSTR positive gastroenteropancreatic neuroendocrine tumor (GEP-NETS) in adults, based on the results of two clinical studies: the NETTER-1 study (NCT01578239) and the Erasmus Medical Center study (MEC 127.545/1993/84); Lutathera® showed beneficial effects on neuroendocrine tumors (NETs) including significantly increasing survival and low radiobiological toxicity.