Refractory Metastatic Gastric Cancer Clinical Trial
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
| Verified date | August 2021 |
| Source | Taiho Oncology, Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 507 |
| Est. completion date | December 19, 2019 |
| Est. primary completion date | April 30, 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| Belarus | Gomel Regional Clinical Oncology Dispensary | Gomel | |
| Belarus | Minsk City Clinical Oncology Dispensary | Minsk | |
| Belarus | Republican center for oncology and medical radiology n.a. Alexandrov | Minsk | |
| Belgium | Clinique universitaire Saint Luc | Brussels | |
| Belgium | Grand Hopital de Charleroi | Charleroi | |
| Belgium | University Hospital Antwerpen | Edegem | |
| Belgium | UZ Leuven | Leuven | |
| Canada | Recherche GCP Research | Montreal | |
| Czechia | Fakultni Nemocniceu sv. Anny v Brne | Brno | |
| Czechia | Faculty Hospital Hradec Kralove | Hradec Králové | |
| Czechia | Fakultní Nemocnice Olomouc | Olomouc | |
| Czechia | Nemocnice Na Homolce | Praha | |
| Czechia | VFN Praha | Praha | |
| France | ICO Paul Papin | Angers cedex 9 | |
| France | Centre Léon Bérard | Lyon | |
| France | Hopital de La Timone | Marseille | |
| France | Hôpital Saint Joseph | Marseille | |
| France | Centre Val D'Aurelle | Montpellier | |
| France | AP-HP - HU La Pitié-Salpêtrière - Charles-Foix | Paris | |
| France | Hopital Europeen Georges Pompidou | Paris | |
| France | Hôpital Saint-Jean | Perpignan | |
| France | Centre medico-chirurgical Magellan | Pessac | |
| France | Centre Eugène Marquis | Rennes Cedex | |
| France | Centre René Gauducheau | Saint Herblain | |
| Germany | Charite Universitaetsmedizin Berlin | Berlin | |
| Germany | Universitaetsklinikum Hamburg-Eppendorf | Hamburg | |
| Germany | Medizinische Hochschule Hannover | Hannover | |
| Germany | Staedtisches Krankenhaus Muenchen Neuperlach | Muenchen | |
| Germany | Technische Universitaet Muenchen | Muenchen | Bayern |
| Germany | Leopoldina-Krankenhaus | Schweinfurt | |
| Germany | Universitaetsklinikum Ulm | Ulm | |
| Ireland | St James Hospital | Dublin | |
| Ireland | The Adelaide and Meath Hospital, Dublin, Incorporating The National Children's Hospital | Dublin 24 | |
| Ireland | Waterford Regional Hospital | Waterford | |
| Israel | Soroka Medical Centre | Beersheba | |
| Israel | Rambam healthcare campus | Haifa | |
| Israel | Wolfson Medical Center | Holon | |
| Israel | Hadassah Ein Karem | Jerusalem | |
| Israel | Rabin MC Belinson Hospital | Petah Tikva | |
| Israel | Sheba Medical Center | Ramat Gan | |
| Israel | Tel Aviv Sourasky Medical Center | Ramat Gan | |
| Italy | IRCCS Centro di Riferimento Oncologico - Aviano | Aviano (PN) | |
| Italy | Humanitas Gavazzeni | Bergamo | |
| Italy | Fondazione Poliambulanza Istituto Ospedaliero | Brescia | |
| Italy | Struttura Complessa di Oncologia | Cremona | |
| Italy | Azienda Ospedaliero - Universitaria Careggi | Firenze | |
| Italy | Azienda Ospedaliera San Martino | Genova | |
| Italy | IRCCS - Istituto Scientifico Romagnolo Per lo Studio e la Cura Dei Tumori (I.R.S.T.) | Meldola (FC) | |
| Italy | Istituto Europeo di Oncologia (IEO) | Milan | |
| Italy | A.O. Ospedale 'Niguarda Ca Granda' | Milano | |
| Italy | A.O.U. Seconda Universita'degli Studi di Napoli | Napoli | |
| Italy | A.O.U. San Luigi Gonzaga | Orbassano (TO) | |
| Italy | Azienda Ospedaliero Universitaria Pisana (AOUP) | Pisa | |
| Italy | A.O.R. San Carlo | Potenza | |
| Italy | Istituto Clinico Humanitas | Rozzano (Mi) | |
| Italy | A.O. della Valtellina e della Valchiavenna Ospedale di Sondrio | Sondrio | |
| Japan | Ibaraki Prefectural Central Hospital | Kasama | Ibaraki |
| Japan | National Cancer Center Hospital East | Kashiwa | Chiba |
| Japan | Iwate Medical University | Morioka | |
| Japan | Osaka General Medical Center | Osaka-shi | Osaka |
| Japan | Osaka National Hospital | Osaka-shi | Osaka |
| Japan | Gunma Prefectural Cancer Center | Ota | Gunma |
| Japan | Sakai City Medical Center | Sakai | Osaka |
| Japan | Toyama University Hospital | Toyama | Toyama |
| Japan | Tochigi Cancer Center | Utsunomiya | Tochigi |
| Poland | Górnoslaskie Centrum Medyczne im. prof. Leszka Gieca | Katowice | |
| Poland | Szpital Uniwersytecki w Krakowie | Kraków | |
| Poland | Regionalny Osrodek Onkologiczny | Lodz | |
| Poland | Szpital MSWiA i Warminsko - Mazurskim Centrum Onkologii w Olsztynie | Olsztyn | |
| Poland | Opolskie centrum Onkologii | Opole | |
| Poland | Maria Sklodowska-Curie Memorial Cancer Center, Institute of Oncology | Warszawa | |
| Portugal | Hospital Garcia de Orta, E.P.E. | Almada | Setubal |
| Portugal | SNS - Hospital Braga | Braga | |
| Portugal | Fundação Champalimaud | Lisboa | |
| Portugal | Hospital da Luz, S.A. | Lisboa | |
| Portugal | Unidade Local de Saúde de Matosinhos E.P.E.- H. Pedro Hispano | Matosinhos | Porto |
| Portugal | Centro Hospitalar de São João, EPE | Porto | |
| Portugal | Centro Hospitalar do Porto, E.P.E | Porto | |
| Portugal | Instituto Português de Oncologia do Porto Francisco Gentil, E.P.E. | Porto | |
| Portugal | Centro Hospitalar de Tras-os-Montes e Alto Douro, EPE | Vila Real | |
| Romania | Centrul De Oncologie "Sfantul Nectarie" | Craiova | Dolj |
| Romania | Spitalul Judetean de Urgenta "Sfantul Ioan cel Nou" Suceava | Suceava | |
| Russian Federation | N.N. Blokhin Russian Cancer Research Center | Moscow | |
| Russian Federation | Nizhegorodsky Regional Oncology Center | Nizhniy Novgorod | |
| Russian Federation | Budget Institution of Healthcare Omsk Region -Clinical Oncology Dispensary | Omsk | |
| Russian Federation | N.N.Petrov Research Institute of Oncology | Saint Petersburg | |
| Russian Federation | North-Western State Medical University n.a. I.I. Mechnikov | Saint Petersburg | |
| Russian Federation | Saint-Petersburgskiy Oncologic Hospital | Saint Petersburg | |
| Russian Federation | Republican Oncology Center | Ufa | |
| Spain | Hospital Universitario Vall d'Hebron | Barcelona | |
| Spain | Hospital Universitario Reina Sofía | Cordoba | |
| Spain | Hospital Universitario La Paz | Madrid | |
| Spain | Hospital Universitario Ramon y Cajal | Madrid | |
| Spain | Hospital Universitario Morales Meseguer | Murcia | |
| Spain | Hospital Universitario Central de Asturias | Oviedo | |
| Spain | Corporacio Parc Tauli | Sabadell | |
| Turkey | Baskent University Adana Practice and Research Centre Kisla | Adana | |
| Turkey | Ankara University Medical Faculty Cebeci Hospital | Ankara | |
| Turkey | Diskapi Yildirim Beyazit Training and Research Hospital | Ankara | |
| Turkey | Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research | Ankara | |
| Turkey | Hacettepe University | Ankara | |
| Turkey | Uludag University Medical Faculty | Bursa | |
| Turkey | Trakya University Medical Faculty Hospital | Edirne | |
| Turkey | Bezmialem Vakif Üniversitesi Tip Fakültesi Hastanesi | Istanbul | |
| Turkey | Istanbul Üniversitesi | Istanbul | |
| Turkey | Marmara University Pendik Training and Research Hospital | Istanbul | |
| Turkey | Dokuz Eylul University Oncology Institute | Izmir | |
| United Kingdom | NHS Grampian | Aberdeen | Scotland |
| United Kingdom | Belfast Health and Social Care Trust - Belfast City Hospital | Belfast | |
| United Kingdom | Leicester Royal Infirmary | Leicester | |
| United Kingdom | Guy's and St Thomas' NHS Foundation Trust | London | |
| United Kingdom | Sarah Cannon Research Institute | London | |
| United Kingdom | The Christie NHS Foundation Trust | Manchester | |
| United Kingdom | East and North Hertfordshire NHS Trust | Northwood | Middlesex |
| United Kingdom | The Royal Marsden NHS Foundation Trust | Sutton | |
| United States | University of Michigan | Ann Arbor | Michigan |
| United States | Alta Bates Summit Comprehensive Cancer Center | Berkeley | California |
| United States | Mount Sinai Hospital Medical Center | Chicago | Illinois |
| United States | Rush University Medical Center | Chicago | Illinois |
| United States | University of Chicago | Chicago | Illinois |
| United States | Coastal Bend Cancer Center | Corpus Christi | Texas |
| United States | St. Jude Heritage Healthcare | Fullerton | California |
| United States | Banner MD Anderson Cancer Center | Gilbert | Arizona |
| United States | 21st Century Oncology | Jacksonville | Florida |
| United States | Dartmouth-Hitchcock Medical Center (DHMC) | Lebanon | New Hampshire |
| United States | University of Kentucky | Lexington | Kentucky |
| United States | Los Angeles Cancer Network | Los Angeles | California |
| United States | University of Southern California - Keck School of Medicine | Los Angeles | California |
| United States | USC/Norris Comprehensive Cancer Center | Los Angeles | California |
| United States | University of Wisconsin | Madison | Wisconsin |
| United States | Medical College of Wisconsin | Milwaukee | Wisconsin |
| United States | Laura & Isaac Perlmutter Cancer Center | New York | New York |
| United States | Memorial Sloan Kettering Cancer Center | New York | New York |
| United States | Illinois CancerCare P.C. | Peoria | Illinois |
| United States | University of Pittsburgh Medical Cancer Center | Pittsburgh | Pennsylvania |
| United States | Roger Williams Medical Center | Providence | Rhode Island |
| United States | Univeristy of Rochester Medical Center | Rochester | New York |
| United States | California Pacific Medical Center | San Francisco | California |
| United States | Wake Forest Baptist Health | Winston-Salem | North Carolina |
| Lead Sponsor | Collaborator |
|---|---|
| Taiho Oncology, Inc. |
United States, Belarus, Belgium, Canada, Czechia, France, Germany, Ireland, Israel, Italy, Japan, Poland, Portugal, Romania, Russian Federation, Spain, Turkey, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Overall Response Rate (ORR) | Overall response rate was defined as the percentage of participants with objective evidence of complete response (CR) or partial response (PR).
CR was defined as the disappearance of all target or non-target lesions. Any pathological lymph nodes for target lesions or all lymph nodes for non-target lesions were non-pathological morphologically that was reduced in size in short axis to < 10 mm. PR was defined as target lesions with at least 30% decrease in the sum of diameters, taking baseline sum diameters as reference. |
From the date of randomization to the cut-off date (maximum duration: up to approximately 46 months), assessed every 8 weeks | |
| Other | Disease Control Rate (DCR) | DCR was defined as the proportion of participants with a best overall response of complete response (CR), partial response (PR), or stable disease (SD). The assessment of DCR was based on Investigator review of radiologic images and following RECIST criteria (version 1.1, 2009). | From the date of randomization to the cut-off date (maximum duration: up to approximately 46 months), assessed every 8 weeks | |
| Other | Time to Deterioration of European Cooperative Oncology Group (ECOG) Performance Status Score From Baseline | The ECOG performance status was used to evaluate participant's disease progression and the effect of the disease on the participant's activities of daily living. It ranges on the scale from 0-5 (0 = normal activity; 1= symptoms but ambulatory; 2= in bed for < 50% of the time; 3= in bed for > 50% of the time; 4= 100% bedridden; 5= dead). Time to definitive deterioration in ECOG performance status score from baseline was defined as a change from 0, 1 to >=2, or from 2 to >=3. | 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) | |
| Other | 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 | EORTC-QLQ-C30 is a cancer-specific instrument with 30 questions for evaluation of new chemotherapy and provides an assessment of participant reported outcome dimensions. First 28 questions used 4-point scale (1=not at all,2=a little,3=quite a bit,4=very much) for evaluating 5 functional scales (physical,role,emotional,cognitive,social), 3 symptom scales (fatigue,nausea/vomiting,pain) and other single items. For each item,high score represented high level of symptomatology/problem. Last 2 questions represented participant's assessment of overall health and QoL, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 observed values and change from baseline for global health status (scoring of questions 29 and 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28). Answers were converted into grading scale, with values between 0 and 100. A high score represented a favorable outcome with a best QoL for participant. | 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) | |
| Other | EORTC Quality of Life Questionnaire - Gastric-specific Module (EORTC QLQ-STO22): Percentage of Participants With Overall Compliance | The Quality of Life Questionnaire Stomach Cancer Module 22 (QLQ-STO22) assessed symptoms and treatment-related side effects commonly reported in participants. There are 22 questions which comprise 5 scales (dysphagia, dietary restrictions, pain QS22, reflux, and anxiety) and 4 single items (dry mouth, hair loss, taste problems, body image). Most questions use 4-point scale (1='Not at all', 2=a little, 3=quite a bit and 4='Very much'). A linear transformation was used to standardize all scores and single-items to a scale of 0 to 100, where higher score=better level of functioning or greater degree of symptoms. | 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) | |
| Primary | 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 | Progression-Free Survival (PFS) | PFS was defined as the time from randomization until the date of first occurrence of investigator-assessed radiological disease progression or death due to any cause, whichever came first. Disease progression as per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) for target lesions were defined as target lesions with at least 20 % relative increase in the sum of diameters with reference to the smallest sum on study, including the baseline sum and this sum demonstrated an absolute increase of at least 5 millimeter (mm) or the appearance of one or more new lesions or Unequivocal progression of existing non-target lesions. All alive participants with no disease progression as of the analysis cut-off date were censored at the last tumor assessment. PFS was estimated by Kaplan-Meier method. | From the date of randomization to the cut-off date (maximum duration: up to approximately 46 months) | |
| Secondary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAE) | Any untoward medical condition that occurs in a participants while participating in a clinical study and does not necessarily have a causal relationship with the use of the study medication was considered an adverse event (AE). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs/TESAEs were defined as events that started on or after treatment or started before treatment and worsened after the start of treatment through 30 days after the last dose of study treatment. | From the first dose of study treatment until 30 days after the last dose of study treatment (maximum duration: up to approximately 46 months) |