Clinical trial NCT02500043: Study of TAS-102 or Placebo Plus BSC in Patients With Metastatic Gastric Cancer
Official title: Randomized, Double-blind, Phase 3 Study Evaluating TAS-102 Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in Patients With Metastatic Gastric Cancer Refractory to Standard Treatments
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Refractory Metastatic Gastric Cancer
Keywords: Gastric Cancer
Metastatic Gastric Cancer
Lead sponsor: Taiho Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2015-07-16
Enrollment: 507
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: This is a multinational, double-blind, two-arm, parallel, randomized, Phase 3 study evaluating the efficacy and safety of TAS-102 plus BSC versus placebo plus BSC in participants with metastatic gastric cancer who have previously received at least 2 prior regimens for advanced disease. Eligible participants will be centrally randomized (2:1) to TAS-102 + BSC (experimental arm) or placebo + BSC (control arm).

Eligibility criteria: Inclusion Criteria:

1. Has histologically confirmed non-resectable, metastatic gastric adenocarcinoma including adenocarcinoma of the gastroesophageal junction.
2. Has previously received at least 2 prior regimens for advanced disease and were refractory to or unable to tolerate their last prior therapy.
3. Has measureable or nonmeasurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
4. Is able to take medications orally (ie, no feeding tube).
5. Has an Eastern Cooperative Oncology Group performance status of 0 or 1.
6. Has adequate organ function as defined by protocol defined labs.
7. 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.

Exclusion Criteria:

1. Has certain serious illnesses or medical conditions
2. 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.
3. Has previously received TAS-102.
4. Has unresolved toxicity of greater than or equal to Common Terminology Criteria for Adverse Events Grade 2 attributed to any prior therapies.
5. Is a pregnant or lactating female.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From the date of randomization to the data cut-off date (maximum duration: up to approximately 46 months)
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: From the date of randomization to the cut-off date (maximum duration: up to approximately 46 months)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAE)
timeFrame: 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:
measure: Overall Response Rate (ORR)
timeFrame: From the date of randomization to the cut-off date (maximum duration: up to approximately 46 months), assessed every 8 weeks
measure: Disease Control Rate (DCR)
timeFrame: From the date of randomization to the cut-off date (maximum duration: up to approximately 46 months), assessed every 8 weeks
measure: Time to Deterioration of European Cooperative Oncology Group (ECOG) Performance Status Score From Baseline
timeFrame: 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)
measure: Change From Baseline in Quality of Life European Organization for Research and Treatment for Cancer (EORTC) QoL Questionnaire Core 30 (QLQ-C30 Score): Global Health Status
timeFrame: Baseline, Day 1 Cycle 2 up to end of treatment (EOT) (within 30 days of last study treatment) and 30-Day safety follow-up visit (maximum duration: up to approximately 46 months)
measure: EORTC Quality of Life Questionnaire - Gastric-specific Module (EORTC QLQ-STO22): Percentage of Participants With Overall Compliance
timeFrame: Baseline, Cycle 1 Day 1 up to end of treatment (EOT) (within 30 days of last study treatment) (maximum duration: up to approximately 46 months)
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Berkeley
country: United States
facility: Alta Bates Summit Comprehensive Cancer Center
state: California
city: Fullerton
country: United States
facility: St. Jude Heritage Healthcare
state: California
city: Los Angeles
country: United States
facility: Los Angeles Cancer Network
state: California
city: Los Angeles
country: United States
facility: University of Southern California - Keck School of Medicine
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Jacksonville
country: United States
facility: 21st Century Oncology
state: Florida
city: Chicago
country: United States
facility: Mount Sinai Hospital Medical Center
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare P.C.
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center (DHMC)
state: New Hampshire
city: New York
country: United States
facility: Laura & Isaac Perlmutter Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: Univeristy of Rochester Medical Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Cancer Center
state: Pennsylvania
city: Providence
country: United States
facility: Roger Williams Medical Center
state: Rhode Island
city: Corpus Christi
country: United States
facility: Coastal Bend Cancer Center
state: Texas
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Gomel
country: Belarus
facility: Gomel Regional Clinical Oncology Dispensary
city: Minsk
country: Belarus
facility: Minsk City Clinical Oncology Dispensary
city: Minsk
country: Belarus
facility: Republican center for oncology and medical radiology n.a. Alexandrov
city: Brussels
country: Belgium
facility: Clinique universitaire Saint Luc
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi
city: Edegem
country: Belgium
facility: University Hospital Antwerpen
city: Leuven
country: Belgium
facility: UZ Leuven
city: Montreal
country: Canada
facility: Recherche GCP Research
city: Brno
country: Czechia
facility: Fakultni Nemocniceu sv. Anny v Brne
city: Hradec Králové
country: Czechia
facility: Faculty Hospital Hradec Kralove
city: Olomouc
country: Czechia
facility: Fakultní Nemocnice Olomouc
city: Praha
country: Czechia
facility: Nemocnice Na Homolce
city: Praha
country: Czechia
facility: VFN Praha
city: Angers cedex 9
country: France
facility: ICO Paul Papin
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Hopital de La Timone
city: Marseille
country: France
facility: Hôpital Saint Joseph
city: Montpellier
country: France
facility: Centre Val D'Aurelle
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou
city: Paris
country: France
facility: AP-HP - HU La Pitié-Salpêtrière - Charles-Foix
city: Perpignan
country: France
facility: Hôpital Saint-Jean
city: Pessac
country: France
facility: Centre medico-chirurgical Magellan
city: Rennes Cedex
country: France
facility: Centre Eugène Marquis
city: Saint Herblain
country: France
facility: Centre René Gauducheau
city: Muenchen
country: Germany
facility: Technische Universitaet Muenchen
state: Bayern
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Muenchen
country: Germany
facility: Staedtisches Krankenhaus Muenchen Neuperlach
city: Schweinfurt
country: Germany
facility: Leopoldina-Krankenhaus
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
city: Dublin 24
country: Ireland
facility: The Adelaide and Meath Hospital, Dublin, Incorporating The National Children's Hospital
city: Dublin
country: Ireland
facility: St James Hospital
city: Waterford
country: Ireland
facility: Waterford Regional Hospital
city: Beersheba
country: Israel
facility: Soroka Medical Centre
city: Haifa
country: Israel
facility: Rambam healthcare campus
city: Holon
country: Israel
facility: Wolfson Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Ein Karem
city: Petah Tikva
country: Israel
facility: Rabin MC Belinson Hospital
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Ramat Gan
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Aviano (PN)
country: Italy
facility: IRCCS Centro di Riferimento Oncologico - Aviano
city: Bergamo
country: Italy
facility: Humanitas Gavazzeni
city: Brescia
country: Italy
facility: Fondazione Poliambulanza Istituto Ospedaliero
city: Cremona
country: Italy
facility: Struttura Complessa di Oncologia
city: Firenze
country: Italy
facility: Azienda Ospedaliero - Universitaria Careggi
city: Genova
country: Italy
facility: Azienda Ospedaliera San Martino
city: Meldola (FC)
country: Italy
facility: IRCCS - Istituto Scientifico Romagnolo Per lo Studio e la Cura Dei Tumori (I.R.S.T.)
city: Milano
country: Italy
facility: A.O. Ospedale 'Niguarda Ca Granda'
city: Milan
country: Italy
facility: Istituto Europeo di Oncologia (IEO)
city: Napoli
country: Italy
facility: A.O.U. Seconda Universita'degli Studi di Napoli
city: Orbassano (TO)
country: Italy
facility: A.O.U. San Luigi Gonzaga
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana (AOUP)
city: Potenza
country: Italy
facility: A.O.R. San Carlo
city: Rozzano (Mi)
country: Italy
facility: Istituto Clinico Humanitas
city: Sondrio
country: Italy
facility: A.O. della Valtellina e della Valchiavenna Ospedale di Sondrio
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Ōta
country: Japan
facility: Gunma Prefectural Cancer Center
state: Gunma
city: Kasama
country: Japan
facility: Ibaraki Prefectural Central Hospital
state: Ibaraki
city: Osaka-shi
country: Japan
facility: Osaka National Hospital
state: Osaka
city: Osaka-shi
country: Japan
facility: Osaka General Medical Center
state: Osaka
city: Sakai
country: Japan
facility: Sakai City Medical Center
state: Osaka
city: Utsunomiya
country: Japan
facility: Tochigi Cancer Center
state: Tochigi
city: Tōyama
country: Japan
facility: Toyama University Hospital
state: Toyama
city: Morioka
country: Japan
facility: Iwate Medical University
city: Katowice
country: Poland
facility: Górnoslaskie Centrum Medyczne im. prof. Leszka Gieca
city: Kraków
country: Poland
facility: Szpital Uniwersytecki w Krakowie
city: Lodz
country: Poland
facility: Regionalny Osrodek Onkologiczny
city: Olsztyn
country: Poland
facility: Szpital MSWiA i Warminsko - Mazurskim Centrum Onkologii w Olsztynie
city: Opole
country: Poland
facility: Opolskie centrum Onkologii
city: Warszawa
country: Poland
facility: Maria Sklodowska-Curie Memorial Cancer Center, Institute of Oncology
city: Matosinhos
country: Portugal
facility: Unidade Local de Saúde de Matosinhos E.P.E.- H. Pedro Hispano
state: Porto
city: Almada
country: Portugal
facility: Hospital Garcia de Orta, E.P.E.
state: Setubal
city: Braga
country: Portugal
facility: SNS - Hospital Braga
city: Lisboa
country: Portugal
facility: Fundação Champalimaud
city: Lisboa
country: Portugal
facility: Hospital da Luz, S.A.
city: Porto
country: Portugal
facility: Centro Hospitalar do Porto, E.P.E
city: Porto
country: Portugal
facility: Instituto Português de Oncologia do Porto Francisco Gentil, E.P.E.
city: Porto
country: Portugal
facility: Centro Hospitalar de São João, EPE
city: Vila Real
country: Portugal
facility: Centro Hospitalar de Tras-os-Montes e Alto Douro, EPE
city: Craiova
country: Romania
facility: Centrul De Oncologie "Sfantul Nectarie"
state: Dolj
city: Suceava
country: Romania
facility: Spitalul Judetean de Urgenta "Sfantul Ioan cel Nou" Suceava
city: Moscow
country: Russian Federation
facility: N.N. Blokhin Russian Cancer Research Center
city: Nizhniy Novgorod
country: Russian Federation
facility: Nizhegorodsky Regional Oncology Center
city: Omsk
country: Russian Federation
facility: Budget Institution of Healthcare Omsk Region -Clinical Oncology Dispensary
city: Saint Petersburg
country: Russian Federation
facility: North-Western State Medical University n.a. I.I. Mechnikov
city: Saint Petersburg
country: Russian Federation
facility: N.N.Petrov Research Institute of Oncology
city: Saint Petersburg
country: Russian Federation
facility: Saint-Petersburgskiy Oncologic Hospital
city: Ufa
country: Russian Federation
facility: Republican Oncology Center
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Murcia
country: Spain
facility: Hospital Universitario Morales Meseguer
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Sabadell
country: Spain
facility: Corporacio Parc Tauli
city: Adana
country: Turkey
facility: Baskent University Adana Practice and Research Centre Kisla
city: Ankara
country: Turkey
facility: Ankara University Medical Faculty Cebeci Hospital
city: Ankara
country: Turkey
facility: Hacettepe University
city: Ankara
country: Turkey
facility: Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research
city: Ankara
country: Turkey
facility: Diskapi Yildirim Beyazit Training and Research Hospital
city: Bursa
country: Turkey
facility: Uludag University Medical Faculty
city: Edirne
country: Turkey
facility: Trakya University Medical Faculty Hospital
city: İstanbul
country: Turkey
facility: Istanbul Üniversitesi
city: Istanbul
country: Turkey
facility: Bezmialem Vakif Üniversitesi Tip Fakültesi Hastanesi
city: İstanbul
country: Turkey
facility: Marmara University Pendik Training and Research Hospital
city: Izmir
country: Turkey
facility: Dokuz Eylul University Oncology Institute
city: Northwood
country: United Kingdom
facility: East and North Hertfordshire NHS Trust
state: Middlesex
city: Aberdeen
country: United Kingdom
facility: NHS Grampian
state: Scotland
city: Belfast
country: United Kingdom
facility: Belfast Health and Social Care Trust - Belfast City Hospital
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.