NCT04042714

TAS-102 in Extrapulmonary Neuroendocrine Carcinoma

An Open-label, Phase II Investigation of TAS-102 in Patients With High Grade, Extrapulmonary Neuroendocrine Carcinoma

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: Baylor Research Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• High-grade Extra Pulmonary Neuroendocrine Cancer

Interventions

Type	Name	Description
DRUG	All patients- TAS-102	Patients will receive TAS-102, Orally, BID for 5 days a week with 2 days rest for 14 days, followed by a 14-day rest treatment cycle. Treatment may continue until disease progresses, intolerable toxicity is developed, or if the patient becomes pregnant or dies.

Timeline

• Start date: 2019-08-15
• Primary completion: 2025-09-15
• Completion: 2025-10-15
• First posted: 2019-08-02
• Last updated: 2025-11-04

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study