High-grade Extra Pulmonary Neuroendocrine Cancer Clinical Trial
Official title:
An Open-label, Phase II Investigation of TAS-102 in Patients With High Grade, Extrapulmonary Neuroendocrine Carcinoma
The purpose of this study is to test the safety and efficacy of drug, TAS-102 (trifluridine/tipiracil), in patients with extrapulmonary (outside the lung) high-grade neuroendocrine cancer. TAS-102 demonstrated improved survival and tolerability in patients with colorectal cancer and is currently approved by the FDA and marketed under the brand name Lonsurf for the treatment of patients with metastatic colorectal cancer (mCRC). Recently, a study evaluating TAS-102 showed a case of complete remission of high-grade NEC. Given the safety profile of TAS-102 and the remarkable single agent activity in a disease with otherwise dismal outcomes, we hope that TAS-102 may show tolerability and efficacy in neuro-endocrine cancer and propose further exploration in patients with extrapulmonary (outside the lung) high-grade neuroendocrine cancer.
Neuroendocrine tumors are highly prevalent cancer showing heterogeneous array of behaviors.
For intermediate/high grade and poorly differentiated neuroendocrine carcinomas (NEC) that
occur outside the lung, there is no acceptable standard of care. Most patients are treated
with a platinum-based chemotherapy in the front-line setting and evidence for therapies in
the second line setting is minimal representing a significant unmet need. However, the
response rates have been unsatisfactory with progression-free survival of only 2.3 to 6.2
months, and there is an unmet need for an effective treatment for patients with refractory
disease.
TAS-102 is a novel combination medicinal product consisting of a thymidine-based nucleoside
analogue (trifluridine; FTD) as the active component and the thymidine phosphorylase
inhibitor tipiracil hydrochloride (TPI) that has shown promising activity in phase I trials
in patients with solid tumors and phase II in patients with gastric cancer. FTD enters cancer
cells, interferes with DNA synthesis, inhibits cell proliferation and inhibit tumor growth.
TPI helps FTD sustain its level in cells without degradation by thymidine phosphorylase
(Tpase).Thus TAS-102 uses dual approach to inhibit rapid degradation of trifluridine and
subsequent tumor growth.
Given the safety profile and efficacy, the study is designed to explore/evaluate efficacy of
TAS-102 and identify characteristics of patients who may respond to this treatment.
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