CLINICAL TRIALS PROFILE FOR TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE

All Clinical Trials for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT03297710 ↗	TAS-102 and Radiation Therapy in Treating Patients With Rectal Cancer That Is Locally Recurrent, Metastatic, or Cannot Be Removed by Surgery	Active, not recruiting	National Cancer Institute (NCI)	Phase 1	2017-12-11	This phase I trial studies the side effects and best dose of trifluridine/tipiracil hydrochloride combination agent TAS-102 (TAS-102) when given together with radiation therapy in treating patients with rectal cancer that has come back, spread to other places in the body, or cannot be removed by surgery. Drugs used in chemotherapy, such as TAS-102, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving TAS-102 with radiation therapy may kill more tumor cells.
NCT03297710 ↗	TAS-102 and Radiation Therapy in Treating Patients With Rectal Cancer That Is Locally Recurrent, Metastatic, or Cannot Be Removed by Surgery	Active, not recruiting	Mayo Clinic	Phase 1	2017-12-11	This phase I trial studies the side effects and best dose of trifluridine/tipiracil hydrochloride combination agent TAS-102 (TAS-102) when given together with radiation therapy in treating patients with rectal cancer that has come back, spread to other places in the body, or cannot be removed by surgery. Drugs used in chemotherapy, such as TAS-102, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving TAS-102 with radiation therapy may kill more tumor cells.
NCT03278106 ↗	TAS-102 in Treating Advanced Biliary Tract Cancers	Active, not recruiting	National Cancer Institute (NCI)	Phase 2	2017-10-20	This phase II trial studies how well trifluridine/tipiracil hydrochloride combination agent TAS-102 (TAS-102) works in treating participants with biliary tract cancers that have spread to other places in the body. Drugs used in the chemotherapy, such as trifluridine/tipiracil hydrochloride combination agent TAS-102, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
NCT03278106 ↗	TAS-102 in Treating Advanced Biliary Tract Cancers	Active, not recruiting	Mayo Clinic	Phase 2	2017-10-20	This phase II trial studies how well trifluridine/tipiracil hydrochloride combination agent TAS-102 (TAS-102) works in treating participants with biliary tract cancers that have spread to other places in the body. Drugs used in the chemotherapy, such as trifluridine/tipiracil hydrochloride combination agent TAS-102, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
NCT03306394 ↗	A Study of Trifluridine/Tipiracil (Also Known as S 95005 or TAS-102) in Patients With a Pretreated Colorectal Cancer That Has Spread (Metastatic).	Completed	ADIR, a Servier Group company	Phase 3	2016-10-18	The purpose of this study is to collect additional safety and efficacy data during treatment with trifluridine / tipiracil in patients with a pretreated metastatic colorectal cancer (mCRC). Eligible patients may receive an early access to trifluridine / tipiracil through this clinical study until progression of disease, unacceptable toxicity, investigator decision, patient refusal or until market authorization or reimbursement has been granted by the relevant Authority of the country where that patient is treated or until trifluridine / tipiracil is available by a doctor's prescription or can be accessed from another source or Sponsor decision.
NCT02654639 ↗	Ph 2 Study of TAS-102 / Bevacizumab Maintenance Therapy Post Induction Chemotherapy in Metastatic Colorectal Cancer	Terminated	Georgetown University	Phase 2	2016-02-01	Phase II study of TAS-102 plus bevacizumab switch maintenance therapy in patients with mCRC
NCT01955837 ↗	Study of Trifluridine/Tipiracil (TAS-102) in Patients With Metastatic Colorectal Cancer in Asia	Completed	Taiho Pharmaceutical Co., Ltd.	Phase 3	2013-09-01	To compare the effects of TAS-102 with placebo in patients with metastatic colorectal cancer refractory or intolerable to standard chemotherapies.

Clinical Trial Conditions for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE

Condition Name

Condition Name for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE
Intervention	Trials
Metastatic Colorectal Cancer	12
Colorectal Cancer	7
Stage IVC Colorectal Cancer AJCC v8	6
Stage IV Colorectal Cancer AJCC v8	6

Condition MeSH

Condition MeSH for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE
Intervention	Trials
Colorectal Neoplasms	39
Adenocarcinoma	17
Colonic Neoplasms	8
Carcinoma	8

Clinical Trial Locations for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE

Trials by Country

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Trials by Country for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE
Location	Trials
United States	111
Italy	28
China	25
Japan	18
Australia	11

Trials by US State

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−

Trials by US State for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE
Location	Trials
California	10
Minnesota	8
Arizona	8
Florida	8
Texas	8

Clinical Trial Progress for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE

Clinical Trial Phase

Clinical Trial Phase for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE
Clinical Trial Phase	Trials
Phase 3	11
Phase 2	33
Phase 1/Phase 2	5

Clinical Trial Status

Clinical Trial Status for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE
Clinical Trial Phase	Trials
Recruiting	27
Not yet recruiting	14
Active, not recruiting	6

Clinical Trial Sponsors for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE

Sponsor Name

Sponsor Name for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE
Sponsor	Trials
National Cancer Institute (NCI)	14
Servier	4
Mayo Clinic	4

Sponsor Type

Sponsor Type for TIPIRACIL HYDROCHLORIDE AND TRIFLURIDINE
Sponsor	Trials
Other	55
Industry	30
NIH	14

Trifluridine/Tipiracil: A Comprehensive Update on Clinical Trials, Market Analysis, and Projections

Introduction

Trifluridine/tipiracil, known by the brand name LONSURF, is a novel oral chemotherapeutic agent that has revolutionized the treatment of metastatic colorectal cancer (mCRC). This combination therapy, comprising trifluridine, a thymidine-based nucleoside analogue, and tipiracil, a thymidine phosphorylase inhibitor, has shown significant promise in improving survival outcomes for patients with refractory mCRC.

Mechanism of Action

The synergy between trifluridine and tipiracil is crucial to their therapeutic efficacy. Trifluridine, after intracellular phosphorylation, is incorporated into DNA, causing DNA dysfunction and leading to cytotoxicity. Tipiracil enhances the bioavailability of trifluridine by inhibiting its breakdown by thymidine phosphorylase, thereby increasing the intracellular concentration of active trifluridine[1][2][5].

Clinical Trials: Key Findings

RECOURSE Trial

The phase III RECOURSE trial was a pivotal study that evaluated the efficacy and safety of trifluridine/tipiracil (TAS-102) in patients with refractory mCRC. This global, double-blinded, randomized, placebo-controlled study involved 800 patients and demonstrated that TAS-102 significantly prolonged overall survival (OS) and progression-free survival (PFS) compared to placebo. The median OS was 7.1 months in the TAS-102 group versus 5.3 months in the placebo group, with a hazard ratio of 0.68[2][5].

SUNLIGHT Trial

The SUNLIGHT trial further built on the success of the RECOURSE trial by investigating the combination of trifluridine/tipiracil with bevacizumab (an anti-VEGF agent) in patients with refractory mCRC. This randomized, open-label trial showed a statistically significant improvement in OS and PFS when compared to trifluridine/tipiracil monotherapy. The median OS was 10.8 months in the combination arm versus 7.5 months in the monotherapy arm, with a hazard ratio of 0.61[1][4].

MODURATE Study

The MODURATE phase Ib study explored the efficacy and safety of combining trifluridine/tipiracil with irinotecan and bevacizumab in patients with mCRC who had failed previous treatments. The study demonstrated comparable antitumor activity to the standard FOLFIRI regimen and identified a recommended phase II dose for the combination therapy[3].

Safety Profile

The safety profile of trifluridine/tipiracil, both as a monotherapy and in combination with bevacizumab, has been extensively evaluated. Common adverse events include neutropenia, anemia, thrombocytopenia, fatigue, nausea, and abdominal pain. These adverse events are generally manageable, and no treatment-related deaths were reported in the SUNLIGHT trial[1][2][4].

Market Analysis

Regulatory Approvals

Trifluridine/tipiracil has received regulatory approvals in multiple regions, including the USA (September 2015), the EU (April 2016), and Japan (March 2014). The recent FDA approval for the combination of trifluridine/tipiracil with bevacizumab further solidifies its position in the treatment landscape of mCRC[4][5].

Market Penetration

Given its efficacy and safety profile, trifluridine/tipiracil has become a significant player in the mCRC market. It is particularly valued for its oral administration, which offers a more convenient treatment option compared to intravenous chemotherapies. The drug is registered for use in over 93 countries, indicating its global acceptance and market penetration[2].

Competitive Landscape

The mCRC treatment market is highly competitive, with several chemotherapeutic agents and targeted therapies available. However, trifluridine/tipiracil's unique mechanism of action and its ability to overcome resistance to standard chemotherapies, such as 5-fluorouracil (5-FU), position it as a valuable option in the treatment continuum[1][5].

Projections and Future Outlook

Increasing Adoption

The combination of trifluridine/tipiracil with bevacizumab is expected to see increased adoption, given the significant survival benefits demonstrated in clinical trials. This combination is likely to become a standard of care for patients with refractory mCRC who have failed previous treatments[1][4].

Ongoing and Future Clinical Trials

Several ongoing and planned clinical trials are exploring the potential of trifluridine/tipiracil in various gastrointestinal cancers and in combination with other therapeutic agents. These studies aim to further elucidate the role of this combination in the broader cancer treatment landscape[3][5].

Real-World Evidence

Real-world studies, such as the one conducted in Romania, have corroborated the findings of clinical trials, demonstrating the efficacy and safety of trifluridine/tipiracil in daily clinical practice. Such evidence supports the long-term use and acceptance of this therapy in diverse patient populations[2].

Key Takeaways

• Efficacy: Trifluridine/tipiracil has shown significant improvements in OS and PFS in patients with refractory mCRC.
• Safety: The combination therapy with bevacizumab has a manageable safety profile with common adverse events such as neutropenia and fatigue.
• Market Position: Approved in over 93 countries, trifluridine/tipiracil is a key player in the mCRC treatment market.
• Future Outlook: Expected to see increased adoption, especially in combination with bevacizumab, and ongoing trials will further define its role in cancer treatment.

FAQs

What is the mechanism of action of trifluridine/tipiracil?

Trifluridine/tipiracil works by trifluridine being incorporated into DNA after phosphorylation, causing DNA dysfunction, while tipiracil inhibits thymidine phosphorylase to enhance trifluridine's bioavailability[1][2][5].

What are the key findings of the SUNLIGHT trial?

The SUNLIGHT trial demonstrated a statistically significant improvement in OS and PFS when trifluridine/tipiracil was combined with bevacizumab compared to trifluridine/tipiracil monotherapy[1][4].

What are the common adverse events associated with trifluridine/tipiracil?

Common adverse events include neutropenia, anemia, thrombocytopenia, fatigue, nausea, and abdominal pain[1][2][4].

Is trifluridine/tipiracil approved for use in combination with other therapies?

Yes, trifluridine/tipiracil is approved for use in combination with bevacizumab for the treatment of mCRC, and ongoing trials are exploring its use with other agents like irinotecan[1][3][4].

What is the current market position of trifluridine/tipiracil?

Trifluridine/tipiracil is registered for use in over 93 countries and has become a significant player in the mCRC treatment market due to its efficacy and convenience of oral administration[2][5].

Sources

1. Touch Oncology: Trifluridine/Tipiracil and Bevacizumab in Adults with Refractory Metastatic Colorectal Cancer[1].
2. Frontiers in Pharmacology: Trifluridine/tipiracil as a therapeutic option in real life setting of metastatic colorectal cancer: An efficacy and safety analysis[2].
3. Oxford Academic: Bevacizumab, Irinotecan, and Biweekly Trifluridine/Tipiracil for Metastatic Colorectal Cancer[3].
4. FDA: FDA approves trifluridine and tipiracil with bevacizumab for previously treated metastatic colorectal cancer[4].
5. Future Oncology: Trifluridine/tipiracil: An emerging strategy for the management of metastatic colorectal cancer[5].