Study of TAS-102 or Placebo Plus BSC in Patients With Metastatic Gastric Cancer

NCT02500043 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: TO-TAS-102-3022015-002683-16
• Study Type: interventional
• Target: 507
• Locations: 17 countries
• Sites: 135

Brief Summary

The purpose of this trial is to compare the effects of TAS-102 and best supportive care (BSC) with Placebo (an inactive drug) and best supportive care on metastatic gastric cancer.

Conditions

Refractory Metastatic Gastric Cancer

Keywords

Gastric Cancer; Metastatic Gastric Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  OS was defined as the time from the date of randomization to the date of death due to any cause. Participants without documented death were censored at last follow-up or cut-off date, whichever comes first. OS was estimated by Kaplan-Meier method.

  From the date of randomization to the data cut-off date (maximum duration: up to approximately 46 months)

Secondary Outcomes (2)

• Progression-Free Survival (PFS)

  From the date of randomization to the cut-off date (maximum duration: up to approximately 46 months)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAE)

  From the first dose of study treatment until 30 days after the last dose of study treatment (maximum duration: up to approximately 46 months)

Other Outcomes (5)

• Overall Response Rate (ORR)

  From the date of randomization to the cut-off date (maximum duration: up to approximately 46 months), assessed every 8 weeks

• Disease Control Rate (DCR)

  From the date of randomization to the cut-off date (maximum duration: up to approximately 46 months), assessed every 8 weeks

• Time to Deterioration of European Cooperative Oncology Group (ECOG) Performance Status Score From Baseline

  At the time of randomization (Day 1 Cycle 1) and within 24 hours prior to start of study treatment in every cycle (maximum duration: up to approximately 46 months)

Study Arms (2)

TAS-102+BSC

EXPERIMENTAL

Participants received 35 milligrams per meter square (mg/m\^2) of TAS-102 tablets orally twice daily (BID) for 5 days per week (i.e., from Days 1 to 5 and Days 8 to 12) for 2 weeks followed by 14 days rest in each 28-day cycle along with BSC until a discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met.

Drug: TAS-102

Placebo+BSC

EXPERIMENTAL

Participants received 35 mg/m\^2 of matching placebo for TAS-102 tablets orally BID for 5 days per week (i.e., from Days 1 to 5 and Days 8 to 12) for 2 weeks followed by 14 days rest in each 28-day cycle along with BSC until discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met.

Drug: Placebo

Interventions

TAS-102 DRUG

35 mg/m2/dose of TAS-102 orally, twice daily on days 1-5 and days 8-12 of each 28-day cycle.

TAS-102+BSC

Placebo DRUG

35 mg/m2/dose of placebo orally, twice daily on days 1-5 and days 8-12 of each 28-day cycle.

Placebo+BSC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has histologically confirmed non-resectable, metastatic gastric adenocarcinoma including adenocarcinoma of the gastroesophageal junction.
• Has previously received at least 2 prior regimens for advanced disease and were refractory to or unable to tolerate their last prior therapy.
• Has measureable or nonmeasurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
• Is able to take medications orally (ie, no feeding tube).
• Has an Eastern Cooperative Oncology Group performance status of 0 or 1.
• Has adequate organ function as defined by protocol defined labs.
• Women of childbearing potential must have a negative pregnancy test and must agree to adequate birth control if conception is possible. Males must agree to adequate birth control.

You may not qualify if:

• Has certain serious illnesses or medical conditions
• Has had certain other recent treatment e.g. major surgery, anticancer therapy, extended field radiation, received investigational agent within the specified time frames prior to study drug administration.
• Has previously received TAS-102.
• Has unresolved toxicity of greater than or equal to Common Terminology Criteria for Adverse Events Grade 2 attributed to any prior therapies.
• Is a pregnant or lactating female.

Sponsors & Collaborators

• Taiho Oncology, Inc.: lead

Study Sites (139)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

Alta Bates Summit Comprehensive Cancer Center

Berkeley, California, 94704, United States

Location

St. Jude Heritage Healthcare

Fullerton, California, 92835, United States

Location

Los Angeles Cancer Network

Los Angeles, California, 90017, United States

Location

University of Southern California - Keck School of Medicine

Los Angeles, California, 90033, United States

Location

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

California Pacific Medical Center

San Francisco, California, 94109, United States

Location

21st Century Oncology

Jacksonville, Florida, 32204, United States

Location

Mount Sinai Hospital Medical Center

Chicago, Illinois, 60608, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Illinois CancerCare P.C.

Peoria, Illinois, 61615, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Dartmouth-Hitchcock Medical Center (DHMC)

Lebanon, New Hampshire, 03756, United States

Location

Laura & Isaac Perlmutter Cancer Center

New York, New York, 10016, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Univeristy of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

University of Pittsburgh Medical Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Roger Williams Medical Center

Providence, Rhode Island, 02908, United States

Location

Coastal Bend Cancer Center

Corpus Christi, Texas, 78404, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792-0001, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226-3522, United States

Location

Gomel Regional Clinical Oncology Dispensary

Homyel, 246012, Belarus

Location

Minsk City Clinical Oncology Dispensary

Minsk, 220013, Belarus

Location

Republican center for oncology and medical radiology n.a. Alexandrov

Minsk, 223040, Belarus

Location

Clinique universitaire Saint Luc

Brussels, Belgium

Location

Grand Hopital de Charleroi

Charleroi, 6000, Belgium

Location

University Hospital Antwerpen

Edegem, B-2650, Belgium

Location

UZ Leuven

Leuven, Belgium

Location

Recherche GCP Research

Montreal, H1M 1M1, Canada

Location

Fakultni Nemocniceu sv. Anny v Brne

Brno, 62100, Czechia

Location

Faculty Hospital Hradec Kralove

Hradec Králové, 50005, Czechia

Location

Fakultní Nemocnice Olomouc

Olomouc, 77520, Czechia

Location

Nemocnice Na Homolce

Prague, Czechia

Location

VFN Praha

Prague, Czechia

Location

ICO Paul Papin

Angers, 49933, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Hopital de La Timone

Marseille, 13005, France

Location

Hôpital Saint Joseph

Marseille, 13008, France

Location

Centre Val D'Aurelle

Montpellier, 34298, France

Location

Hopital Europeen Georges Pompidou

Paris, 75015, France

Location

AP-HP - HU La Pitié-Salpêtrière - Charles-Foix

Paris, 75651, France

Location

Hôpital Saint-Jean

Perpignan, 66000, France

Location

Centre medico-chirurgical Magellan

Pessac, 33604, France

Location

Centre Eugène Marquis

Rennes, 35042, France

Location

Centre René Gauducheau

Saint-Herblain, France

Location

Technische Universitaet Muenchen

Munich, Bavaria, 81675, Germany

Location

Charite Universitaetsmedizin Berlin

Berlin, 13353, Germany

Location

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Staedtisches Krankenhaus Muenchen Neuperlach

München, 81737, Germany

Location

Leopoldina-Krankenhaus

Schweinfurt, 97422, Germany

Location

Universitaetsklinikum Ulm

Ulm, 89081, Germany

Location

St James Hospital

Dublin, Ireland

Location

The Adelaide and Meath Hospital, Dublin, Incorporating The National Children's Hospital

Dublin, Ireland

Location

Waterford Regional Hospital

Waterford, Ireland

Location

Soroka Medical Centre

Beersheba, 8410101, Israel

Location

Rambam healthcare campus

Haifa, 31096, Israel

Location

Wolfson Medical Center

Holon, 5822012, Israel

Location

Hadassah Ein Karem

Jerusalem, 91120, Israel

Location

Rabin MC Belinson Hospital

Petah Tikva, 49100, Israel

Location

Sheba Medical Center

Ramat Gan, 52520, Israel

Location

Tel Aviv Sourasky Medical Center

Ramat Gan, 64239, Israel

Location

IRCCS Centro di Riferimento Oncologico - Aviano

Aviano (PN), 33081, Italy

Location

Humanitas Gavazzeni

Bergamo, 24125, Italy

Location

Fondazione Poliambulanza Istituto Ospedaliero

Brescia, 25124, Italy

Location

Struttura Complessa di Oncologia

Cremona, 26100, Italy

Location

Azienda Ospedaliero - Universitaria Careggi

Florence, 50134, Italy

Location

Azienda Ospedaliera San Martino

Genova, 16132, Italy

Location

IRCCS - Istituto Scientifico Romagnolo Per lo Studio e la Cura Dei Tumori (I.R.S.T.)

Meldola (FC), 47014, Italy

Location

Istituto Europeo di Oncologia (IEO)

Milan, 20141, Italy

Location

A.O. Ospedale 'Niguarda Ca Granda'

Milan, 20162, Italy

Location

A.O.U. Seconda Universita'degli Studi di Napoli

Napoli, 80131, Italy

Location

A.O.U. San Luigi Gonzaga

Orbassano (TO), 10043, Italy

Location

Azienda Ospedaliero Universitaria Pisana (AOUP)

Pisa, 56126, Italy

Location

A.O.R. San Carlo

Potenza, 85100, Italy

Location

Istituto Clinico Humanitas

Rozzano (Mi), 20089, Italy

Location

A.O. della Valtellina e della Valchiavenna Ospedale di Sondrio

Sondrio, 23100, Italy

Location

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

Location

Gunma Prefectural Cancer Center

Ōta, Gunma, 373-8550, Japan

Location

Ibaraki Prefectural Central Hospital

Kasama, Ibaraki, 309-1793, Japan

Location

Osaka National Hospital

Osaka, Osaka, 540-0006, Japan

Location

Osaka General Medical Center

Osaka, Osaka, 558-8558, Japan

Location

Sakai City Medical Center

Sakai, Osaka, 593-8304, Japan

Location

Tochigi Cancer Center

Utsunomiya, Tochigi, 320-0834, Japan

Location

Toyama University Hospital

Tōyama, Toyama, 930-0194, Japan

Location

Iwate Medical University

Morioka, 020-8505, Japan

Location

Górnoslaskie Centrum Medyczne im. prof. Leszka Gieca

Katowice, 40-635, Poland

Location

Szpital Uniwersytecki w Krakowie

Krakow, 31-531, Poland

Location

Regionalny Osrodek Onkologiczny

Lodz, 93-513, Poland

Location

Szpital MSWiA i Warminsko - Mazurskim Centrum Onkologii w Olsztynie

Olsztyn, 10-228, Poland

Location

Opolskie centrum Onkologii

Opole, 45-060, Poland

Location

Maria Sklodowska-Curie Memorial Cancer Center, Institute of Oncology

Warsaw, 02-781, Poland

Location

Unidade Local de Saúde de Matosinhos E.P.E.- H. Pedro Hispano

Matosinhos Municipality, Porto District, 4464-513, Portugal

Location

Hospital Garcia de Orta, E.P.E.

Almada, Setúbal District, 2805-267, Portugal

Location

SNS - Hospital Braga

Braga, 4710-243, Portugal

Location

Fundação Champalimaud

Lisbon, 1400-038, Portugal

Location

Hospital da Luz, S.A.

Lisbon, 1500-650, Portugal

Location

Centro Hospitalar do Porto, E.P.E

Porto, 4099-001, Portugal

Location

Instituto Português de Oncologia do Porto Francisco Gentil, E.P.E.

Porto, 4200-072, Portugal

Location

Centro Hospitalar de São João, EPE

Porto, 4200-319, Portugal

Location

Centro Hospitalar de Tras-os-Montes e Alto Douro, EPE

Vila Real, 5000-259, Portugal

Location

Centrul De Oncologie "Sfantul Nectarie"

Craiova, Dolj, 200385, Romania

Location

Spitalul Judetean de Urgenta "Sfantul Ioan cel Nou" Suceava

Suceava, 720224, Romania

Location

N.N. Blokhin Russian Cancer Research Center

Moscow, 115478, Russia

Location

Nizhegorodsky Regional Oncology Center

Nizhny Novgorod, Russia

Location

Budget Institution of Healthcare Omsk Region -Clinical Oncology Dispensary

Omsk, 644013, Russia

Location

North-Western State Medical University n.a. I.I. Mechnikov

Saint Petersburg, 195067, Russia

Location

N.N.Petrov Research Institute of Oncology

Saint Petersburg, 197758, Russia

Location

Saint-Petersburgskiy Oncologic Hospital

Saint Petersburg, 197758, Russia

Location

Republican Oncology Center

Ufa, 450054, Russia

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario Reina Sofía

Córdoba, 14004, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Morales Meseguer

Murcia, 30008, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, 33006, Spain

Location

Corporacio Parc Tauli

Sabadell, 08208, Spain

Location

Baskent University Adana Practice and Research Centre Kisla

Adana, 1230, Turkey (Türkiye)

Location

Ankara University Medical Faculty Cebeci Hospital

Ankara, 6100, Turkey (Türkiye)

Location

Hacettepe University

Ankara, 6100, Turkey (Türkiye)

Location

Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research

Ankara, 6200, Turkey (Türkiye)

Location

Diskapi Yildirim Beyazit Training and Research Hospital

Ankara, 6330, Turkey (Türkiye)

Location

Uludag University Medical Faculty

Bursa, 16059, Turkey (Türkiye)

Location

Trakya University Medical Faculty Hospital

Edirne, 22030, Turkey (Türkiye)

Location

Istanbul Üniversitesi

Istanbul, 34098, Turkey (Türkiye)

Location

Bezmialem Vakif Üniversitesi Tip Fakültesi Hastanesi

Istanbul, 34722, Turkey (Türkiye)

Location

Marmara University Pendik Training and Research Hospital

Istanbul, 34890, Turkey (Türkiye)

Location

Dokuz Eylul University Oncology Institute

Izmir, 35340, Turkey (Türkiye)

Location

East and North Hertfordshire NHS Trust

Northwood, Middlesex, HA6 2RN, United Kingdom

Location

NHS Grampian

Aberdeen, Scotland, AB25 2ZN, United Kingdom

Location

Belfast Health and Social Care Trust - Belfast City Hospital

Belfast, SM2 5NG, United Kingdom

Location

Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

Location

Guy's and St Thomas' NHS Foundation Trust

London, SE1 9RT, United Kingdom

Location

Sarah Cannon Research Institute

London, W1G 6AD, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (6)

• Ying T, Xia R, Zhang Y, Dai J, Wang Y, Xie X. Cost-effectiveness analysis of trifluridine/tipiracil in the treatment of heavily pretreated metastatic gastric cancer from the perspective of Chinese healthcare system. BMJ Open. 2024 Nov 7;14(11):e080846. doi: 10.1136/bmjopen-2023-080846.

  PMID: 39510786 DERIVED

• Shitara K, George B, Taieb J, Sundar R, Fakih MG, Makris L, Benhadji KA, Ghidini M. Effects of prior therapies on outcomes with trifluridine/tipiracil in patients with metastatic gastric/gastroesophageal junction cancer in a randomized phase III trial (TAGS). J Cancer Res Clin Oncol. 2023 Sep;149(11):9361-9374. doi: 10.1007/s00432-023-04813-z. Epub 2023 May 22.

  PMID: 37213030 DERIVED

• Tabernero J, Alsina M, Shitara K, Doi T, Dvorkin M, Mansoor W, Arkenau HT, Prokharau A, Ghidini M, Faustino C, Gorbunova V, Zhavrid E, Nishikawa K, Ando T, Yalcin S, Van Cutsem E, Sabater J, Skanji D, Leger C, Amellal N, Ilson DH. Health-related quality of life associated with trifluridine/tipiracil in heavily pretreated metastatic gastric cancer: results from TAGS. Gastric Cancer. 2020 Jul;23(4):689-698. doi: 10.1007/s10120-020-01053-9. Epub 2020 Mar 4.

  PMID: 32128634 DERIVED

• Ilson DH, Tabernero J, Prokharau A, Arkenau HT, Ghidini M, Fujitani K, Van Cutsem E, Thuss-Patience P, Beretta GD, Mansoor W, Zhavrid E, Alsina M, George B, Catenacci D, McGuigan S, Makris L, Doi T, Shitara K. Efficacy and Safety of Trifluridine/Tipiracil Treatment in Patients With Metastatic Gastric Cancer Who Had Undergone Gastrectomy: Subgroup Analyses of a Randomized Clinical Trial. JAMA Oncol. 2020 Jan 1;6(1):e193531. doi: 10.1001/jamaoncol.2019.3531. Epub 2020 Jan 9.

  PMID: 31600365 DERIVED

• Shitara K, Doi T, Dvorkin M, Mansoor W, Arkenau HT, Prokharau A, Alsina M, Ghidini M, Faustino C, Gorbunova V, Zhavrid E, Nishikawa K, Hosokawa A, Yalcin S, Fujitani K, Beretta GD, Cutsem EV, Winkler RE, Makris L, Ilson DH, Tabernero J. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018 Nov;19(11):1437-1448. doi: 10.1016/S1470-2045(18)30739-3. Epub 2018 Oct 21.

  PMID: 30355453 DERIVED

• Bando H, Doi T, Muro K, Yasui H, Nishina T, Yamaguchi K, Takahashi S, Nomura S, Kuno H, Shitara K, Sato A, Ohtsu A. A multicenter phase II study of TAS-102 monotherapy in patients with pre-treated advanced gastric cancer (EPOC1201). Eur J Cancer. 2016 Jul;62:46-53. doi: 10.1016/j.ejca.2016.04.009. Epub 2016 May 19.

  PMID: 27208903 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

trifluridine tipiracil drug combination

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Results Point of Contact

• Title: Taiho Central
• Organization: Taiho Oncology, Inc.

clinicaltrialinfo@taihooncology.com

609-250-7336

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2015
• First Posted: July 16, 2015
• Study Start: February 24, 2016
• Primary Completion: April 30, 2018
• Study Completion: December 19, 2019
• Last Updated: September 3, 2024
• Results First Posted: September 16, 2021

Record last verified: 2024-08

Locations

BE (3); CA (1); TU (11); JP (9); DE (7); IL (7); PT (9); RO (2); IE (3); US (24); PL (6); FR (11); CZ (5); IT (15); GB (8); ES (7); RU (7)