Study of TAS-102 or Placebo Plus BSC in Patients With Metastatic Gastric Cancer
Sponsor
Taiho Oncology, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02500043
Collaborator
(none)
507
139
2
45.8
3.6
0.1
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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).
Study Design
Study Type:
Interventional
Actual Enrollment
:
507 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date
:
Feb 24, 2016
Actual Primary Completion Date
:
Apr 30, 2018
Actual Study Completion Date
:
Dec 19, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: TAS-102+BSC 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
35 mg/m2/dose of TAS-102 orally, twice daily on days 1-5 and days 8-12 of each 28-day cycle.
|
| Experimental: Placebo+BSC 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
35 mg/m2/dose of placebo orally, twice daily on days 1-5 and days 8-12 of each 28-day cycle.
|
Outcome Measures
Primary Outcome Measures
- Overall Survival (OS) [From the date of randomization to the data cut-off date (maximum duration: up to approximately 46 months)]
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.
Secondary Outcome Measures
- Progression-Free Survival (PFS) [From the date of randomization to the cut-off date (maximum duration: up to approximately 46 months)]
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.
- 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)]
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.
Other Outcome Measures
- 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]
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.
- 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]
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).
- 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)]
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.
- 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 [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)]
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.
- EORTC Quality of Life Questionnaire - Gastric-specific Module (EORTC QLQ-STO22): Percentage of Participants With Overall Compliance [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)]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
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.
Exclusion Criteria:
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Banner MD Anderson Cancer Center | Gilbert | Arizona | United States | 85234 |
| 2 | Alta Bates Summit Comprehensive Cancer Center | Berkeley | California | United States | 94704 |
| 3 | St. Jude Heritage Healthcare | Fullerton | California | United States | 92835 |
| 4 | Los Angeles Cancer Network | Los Angeles | California | United States | 90017 |
| 5 | University of Southern California - Keck School of Medicine | Los Angeles | California | United States | 90033 |
| 6 | USC/Norris Comprehensive Cancer Center | Los Angeles | California | United States | 90033 |
| 7 | California Pacific Medical Center | San Francisco | California | United States | 94109 |
| 8 | 21st Century Oncology | Jacksonville | Florida | United States | 32204 |
| 9 | Mount Sinai Hospital Medical Center | Chicago | Illinois | United States | 60608 |
| 10 | Rush University Medical Center | Chicago | Illinois | United States | 60612 |
| 11 | University of Chicago | Chicago | Illinois | United States | 60637 |
| 12 | Illinois CancerCare P.C. | Peoria | Illinois | United States | 61615 |
| 13 | University of Kentucky | Lexington | Kentucky | United States | 40536 |
| 14 | University of Michigan | Ann Arbor | Michigan | United States | 48109 |
| 15 | Dartmouth-Hitchcock Medical Center (DHMC) | Lebanon | New Hampshire | United States | 03756 |
| 16 | Laura & Isaac Perlmutter Cancer Center | New York | New York | United States | 10016 |
| 17 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 18 | Univeristy of Rochester Medical Center | Rochester | New York | United States | 14642 |
| 19 | Wake Forest Baptist Health | Winston-Salem | North Carolina | United States | 27157 |
| 20 | University of Pittsburgh Medical Cancer Center | Pittsburgh | Pennsylvania | United States | 15232 |
| 21 | Roger Williams Medical Center | Providence | Rhode Island | United States | 02908 |
| 22 | Coastal Bend Cancer Center | Corpus Christi | Texas | United States | 78404 |
| 23 | University of Wisconsin | Madison | Wisconsin | United States | 53792-0001 |
| 24 | Medical College of Wisconsin | Milwaukee | Wisconsin | United States | 53226-3522 |
| 25 | Gomel Regional Clinical Oncology Dispensary | Gomel | Belarus | 246012 | |
| 26 | Minsk City Clinical Oncology Dispensary | Minsk | Belarus | 220013 | |
| 27 | Republican center for oncology and medical radiology n.a. Alexandrov | Minsk | Belarus | 223040 | |
| 28 | Clinique universitaire Saint Luc | Brussels | Belgium | ||
| 29 | Grand Hopital de Charleroi | Charleroi | Belgium | 6000 | |
| 30 | University Hospital Antwerpen | Edegem | Belgium | B-2650 | |
| 31 | UZ Leuven | Leuven | Belgium | ||
| 32 | Recherche GCP Research | Montreal | Canada | H1M 1M1 | |
| 33 | Fakultni Nemocniceu sv. Anny v Brne | Brno | Czechia | 62100 | |
| 34 | Faculty Hospital Hradec Kralove | Hradec Králové | Czechia | 50005 | |
| 35 | Fakultní Nemocnice Olomouc | Olomouc | Czechia | 77520 | |
| 36 | Nemocnice Na Homolce | Praha | Czechia | ||
| 37 | VFN Praha | Praha | Czechia | ||
| 38 | ICO Paul Papin | Angers cedex 9 | France | 49933 | |
| 39 | Centre Léon Bérard | Lyon | France | 69008 | |
| 40 | Hopital de La Timone | Marseille | France | 13005 | |
| 41 | Hôpital Saint Joseph | Marseille | France | 13008 | |
| 42 | Centre Val D'Aurelle | Montpellier | France | 34298 | |
| 43 | Hopital Europeen Georges Pompidou | Paris | France | 75015 | |
| 44 | AP-HP - HU La Pitié-Salpêtrière - Charles-Foix | Paris | France | 75651 | |
| 45 | Hôpital Saint-Jean | Perpignan | France | 66000 | |
| 46 | Centre medico-chirurgical Magellan | Pessac | France | 33604 | |
| 47 | Centre Eugène Marquis | Rennes Cedex | France | 35042 | |
| 48 | Centre René Gauducheau | Saint Herblain | France | ||
| 49 | Technische Universitaet Muenchen | Muenchen | Bayern | Germany | 81675 |
| 50 | Charite Universitaetsmedizin Berlin | Berlin | Germany | 13353 | |
| 51 | Universitaetsklinikum Hamburg-Eppendorf | Hamburg | Germany | 20246 | |
| 52 | Medizinische Hochschule Hannover | Hannover | Germany | 30625 | |
| 53 | Staedtisches Krankenhaus Muenchen Neuperlach | Muenchen | Germany | 81737 | |
| 54 | Leopoldina-Krankenhaus | Schweinfurt | Germany | 97422 | |
| 55 | Universitaetsklinikum Ulm | Ulm | Germany | 89081 | |
| 56 | The Adelaide and Meath Hospital, Dublin, Incorporating The National Children's Hospital | Dublin 24 | Ireland | ||
| 57 | St James Hospital | Dublin | Ireland | ||
| 58 | Waterford Regional Hospital | Waterford | Ireland | ||
| 59 | Soroka Medical Centre | Beersheba | Israel | 8410101 | |
| 60 | Rambam healthcare campus | Haifa | Israel | 31096 | |
| 61 | Wolfson Medical Center | Holon | Israel | 5822012 | |
| 62 | Hadassah Ein Karem | Jerusalem | Israel | 91120 | |
| 63 | Rabin MC Belinson Hospital | Petah Tikva | Israel | 49100 | |
| 64 | Sheba Medical Center | Ramat Gan | Israel | 52520 | |
| 65 | Tel Aviv Sourasky Medical Center | Ramat Gan | Israel | 64239 | |
| 66 | IRCCS Centro di Riferimento Oncologico - Aviano | Aviano (PN) | Italy | 33081 | |
| 67 | Humanitas Gavazzeni | Bergamo | Italy | 24125 | |
| 68 | Fondazione Poliambulanza Istituto Ospedaliero | Brescia | Italy | 25124 | |
| 69 | Struttura Complessa di Oncologia | Cremona | Italy | 26100 | |
| 70 | Azienda Ospedaliero - Universitaria Careggi | Firenze | Italy | 50134 | |
| 71 | Azienda Ospedaliera San Martino | Genova | Italy | 16132 | |
| 72 | IRCCS - Istituto Scientifico Romagnolo Per lo Studio e la Cura Dei Tumori (I.R.S.T.) | Meldola (FC) | Italy | 47014 | |
| 73 | A.O. Ospedale 'Niguarda Ca Granda' | Milano | Italy | 20162 | |
| 74 | Istituto Europeo di Oncologia (IEO) | Milan | Italy | 20141 | |
| 75 | A.O.U. Seconda Universita'degli Studi di Napoli | Napoli | Italy | 80131 | |
| 76 | A.O.U. San Luigi Gonzaga | Orbassano (TO) | Italy | 10043 | |
| 77 | Azienda Ospedaliero Universitaria Pisana (AOUP) | Pisa | Italy | 56126 | |
| 78 | A.O.R. San Carlo | Potenza | Italy | 85100 | |
| 79 | Istituto Clinico Humanitas | Rozzano (Mi) | Italy | 20089 | |
| 80 | A.O. della Valtellina e della Valchiavenna Ospedale di Sondrio | Sondrio | Italy | 23100 | |
| 81 | National Cancer Center Hospital East | Kashiwa | Chiba | Japan | 277-8577 |
| 82 | Gunma Prefectural Cancer Center | Ōta | Gunma | Japan | 373-8550 |
| 83 | Ibaraki Prefectural Central Hospital | Kasama | Ibaraki | Japan | 309-1793 |
| 84 | Osaka National Hospital | Osaka-shi | Osaka | Japan | 540-0006 |
| 85 | Osaka General Medical Center | Osaka-shi | Osaka | Japan | 558-8558 |
| 86 | Sakai City Medical Center | Sakai | Osaka | Japan | 593-8304 |
| 87 | Tochigi Cancer Center | Utsunomiya | Tochigi | Japan | 320-0834 |
| 88 | Toyama University Hospital | Tōyama | Toyama | Japan | 930-0194 |
| 89 | Iwate Medical University | Morioka | Japan | 020-8505 | |
| 90 | Górnoslaskie Centrum Medyczne im. prof. Leszka Gieca | Katowice | Poland | 40-635 | |
| 91 | Szpital Uniwersytecki w Krakowie | Kraków | Poland | 31-531 | |
| 92 | Regionalny Osrodek Onkologiczny | Lodz | Poland | 93-513 | |
| 93 | Szpital MSWiA i Warminsko - Mazurskim Centrum Onkologii w Olsztynie | Olsztyn | Poland | 10-228 | |
| 94 | Opolskie centrum Onkologii | Opole | Poland | 45-060 | |
| 95 | Maria Sklodowska-Curie Memorial Cancer Center, Institute of Oncology | Warszawa | Poland | 02-781 | |
| 96 | Unidade Local de Saúde de Matosinhos E.P.E.- H. Pedro Hispano | Matosinhos | Porto | Portugal | 4464-513 |
| 97 | Hospital Garcia de Orta, E.P.E. | Almada | Setubal | Portugal | 2805-267 |
| 98 | SNS - Hospital Braga | Braga | Portugal | 4710-243 | |
| 99 | Fundação Champalimaud | Lisboa | Portugal | 1400-038 | |
| 100 | Hospital da Luz, S.A. | Lisboa | Portugal | 1500-650 | |
| 101 | Centro Hospitalar do Porto, E.P.E | Porto | Portugal | 4099-001 | |
| 102 | Instituto Português de Oncologia do Porto Francisco Gentil, E.P.E. | Porto | Portugal | 4200-072 | |
| 103 | Centro Hospitalar de São João, EPE | Porto | Portugal | 4200-319 | |
| 104 | Centro Hospitalar de Tras-os-Montes e Alto Douro, EPE | Vila Real | Portugal | 5000-259 | |
| 105 | Centrul De Oncologie "Sfantul Nectarie" | Craiova | Dolj | Romania | 200385 |
| 106 | Spitalul Judetean de Urgenta "Sfantul Ioan cel Nou" Suceava | Suceava | Romania | 720224 | |
| 107 | N.N. Blokhin Russian Cancer Research Center | Moscow | Russian Federation | 115478 | |
| 108 | Nizhegorodsky Regional Oncology Center | Nizhniy Novgorod | Russian Federation | ||
| 109 | Budget Institution of Healthcare Omsk Region -Clinical Oncology Dispensary | Omsk | Russian Federation | 644013 | |
| 110 | North-Western State Medical University n.a. I.I. Mechnikov | Saint Petersburg | Russian Federation | 195067 | |
| 111 | N.N.Petrov Research Institute of Oncology | Saint Petersburg | Russian Federation | 197758 | |
| 112 | Saint-Petersburgskiy Oncologic Hospital | Saint Petersburg | Russian Federation | 197758 | |
| 113 | Republican Oncology Center | Ufa | Russian Federation | 450054 | |
| 114 | Hospital Universitario Vall d'Hebron | Barcelona | Spain | 08035 | |
| 115 | Hospital Universitario Reina Sofía | Cordoba | Spain | 14004 | |
| 116 | Hospital Universitario Ramon y Cajal | Madrid | Spain | 28034 | |
| 117 | Hospital Universitario La Paz | Madrid | Spain | 28046 | |
| 118 | Hospital Universitario Morales Meseguer | Murcia | Spain | 30008 | |
| 119 | Hospital Universitario Central de Asturias | Oviedo | Spain | 33006 | |
| 120 | Corporacio Parc Tauli | Sabadell | Spain | 08208 | |
| 121 | Baskent University Adana Practice and Research Centre Kisla | Adana | Turkey | 1230 | |
| 122 | Ankara University Medical Faculty Cebeci Hospital | Ankara | Turkey | 6100 | |
| 123 | Hacettepe University | Ankara | Turkey | 6100 | |
| 124 | Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research | Ankara | Turkey | 6200 | |
| 125 | Diskapi Yildirim Beyazit Training and Research Hospital | Ankara | Turkey | 6330 | |
| 126 | Uludag University Medical Faculty | Bursa | Turkey | 16059 | |
| 127 | Trakya University Medical Faculty Hospital | Edirne | Turkey | 22030 | |
| 128 | Istanbul Üniversitesi | İstanbul | Turkey | 34098 | |
| 129 | Bezmialem Vakif Üniversitesi Tip Fakültesi Hastanesi | Istanbul | Turkey | 34722 | |
| 130 | Marmara University Pendik Training and Research Hospital | İstanbul | Turkey | 34890 | |
| 131 | Dokuz Eylul University Oncology Institute | Izmir | Turkey | 35340 | |
| 132 | East and North Hertfordshire NHS Trust | Northwood | Middlesex | United Kingdom | HA6 2RN |
| 133 | NHS Grampian | Aberdeen | Scotland | United Kingdom | AB25 2ZN |
| 134 | Belfast Health and Social Care Trust - Belfast City Hospital | Belfast | United Kingdom | SM2 5NG | |
| 135 | Leicester Royal Infirmary | Leicester | United Kingdom | LE1 5WW | |
| 136 | Guy's and St Thomas' NHS Foundation Trust | London | United Kingdom | SE1 9RT | |
| 137 | Sarah Cannon Research Institute | London | United Kingdom | W1G 6AD | |
| 138 | The Christie NHS Foundation Trust | Manchester | United Kingdom | M20 4BX | |
| 139 | The Royal Marsden NHS Foundation Trust | Sutton | United Kingdom | SM2 5PT |
Sponsors and Collaborators
- Taiho Oncology, Inc.
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Taiho Oncology, Inc.
ClinicalTrials.gov Identifier:
NCT02500043
Other Study ID Numbers:
- TO-TAS-102-302
- 2015-002683-16
First Posted:
Jul 16, 2015
Last Update Posted:
Sep 16, 2021
Last Verified:
Aug 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Taiho Oncology, Inc.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The study was conducted at study centers in 17 countries. Participants were involved in the study from 24 February 2016 to 19 December 2019. |
|---|---|
| Pre-assignment Detail | Overall, 625 participants were screened, of which 118 were screen failures due to inclusion/exclusion criteria not met and 507 were randomized and treated with TAS-102 or placebo along with Best supportive care (BSC) (BSC was given to prevent, control, or relieve complications and side effects with the intention to maximize quality of life (QoL) without a specific antineoplastic regimen). |
| Arm/Group Title | TAS-102+BSC | Placebo+BSC |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Period Title: Overall Study | ||
| STARTED | 337 | 170 |
| As-Treated (AT) Population | 335 | 168 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 337 | 170 |
Baseline Characteristics
| Arm/Group Title | TAS-102+BSC | Placebo+BSC | Total |
|---|---|---|---|
| Arm/Group Description | Participants received 35 mg/m^2 of 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 a discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met. | 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. | Total of all reporting groups |
| Overall Participants | 337 | 170 | 507 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
62.8
(10.78)
|
62.0
(10.04)
|
62.5
(10.53)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
85
25.2%
|
53
31.2%
|
138
27.2%
|
| Male |
252
74.8%
|
117
68.8%
|
369
72.8%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| White |
244
72.4%
|
113
66.5%
|
357
70.4%
|
| Black/African American |
1
0.3%
|
2
1.2%
|
3
0.6%
|
| Asian |
51
15.1%
|
29
17.1%
|
80
15.8%
|
| Not collectable |
38
11.3%
|
24
14.1%
|
62
12.2%
|
| Other |
3
0.9%
|
2
1.2%
|
5
1%
|
| European Cooperative Oncology Group (ECOG) Performance Status (Count of Participants) | |||
| ECOG Grade 0 |
123
36.5%
|
68
40%
|
191
37.7%
|
| ECOG Grade 1 |
214
63.5%
|
102
60%
|
316
62.3%
|
Outcome Measures
| Title | Overall Survival (OS) |
|---|---|
| Description | 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. |
| Time Frame | From the date of randomization to the data cut-off date (maximum duration: up to approximately 46 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on the ITT population that included all randomized participants, regardless of whether or not study treatment was administered. |
| Arm/Group Title | TAS-102+BSC | Placebo+BSC |
|---|---|---|
| Arm/Group Description | Participants received 35 mg/m^2 of 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 a discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met. | 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. |
| Measure Participants | 337 | 170 |
| Median (95% Confidence Interval) [months] |
5.7
|
3.6
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TAS-102+BSC, Placebo+BSC |
|---|---|---|
| Comments | TAS-102+BSC and Placebo+BSC were compared using the stratified log-rank test using the 3 randomization stratification factors (region, ECOG performance status, and prior treatment with ramucirumab). The hazard ratio was estimated using a stratified Cox's proportional hazard (CPH) model and survival was summarized using Kaplan Meier estimates. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0003 |
| Comments | One-sided P-Value. | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.6917 | |
| Confidence Interval |
(2-Sided) 95% 0.5597 to 0.8548 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Progression-Free Survival (PFS) |
|---|---|
| Description | 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. |
| Time Frame | From the date of randomization to the cut-off date (maximum duration: up to approximately 46 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on the ITT population that included all randomized participants, regardless of whether or not study treatment was administered. |
| Arm/Group Title | TAS-102+BSC | Placebo+BSC |
|---|---|---|
| Arm/Group Description | Participants received 35 mg/m^2 of 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 a discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met. | 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. |
| Measure Participants | 337 | 170 |
| Median (95% Confidence Interval) [months] |
2.0
|
1.8
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TAS-102+BSC, Placebo+BSC |
|---|---|---|
| Comments | TAS-102+BSC and Placebo+BSC were compared using the stratified log-rank test using the 3 randomization stratification factors (region, ECOG performance status, and prior treatment with ramucirumab). The hazard ratio was estimated using a stratified CPH model and survival was summarized using Kaplan Meier estimates. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.5723 | |
| Confidence Interval |
(2-Sided) 95% 0.4674 to 0.7008 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAE) |
|---|---|
| Description | 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. |
| Time Frame | From the first dose of study treatment until 30 days after the last dose of study treatment (maximum duration: up to approximately 46 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on the As-treated (AT) population that included all participants who received at least 1 dose of study treatment. |
| Arm/Group Title | TAS-102+BSC | Placebo+BSC |
|---|---|---|
| Arm/Group Description | Participants received 35 mg/m^2 of 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 a discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met. | 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. |
| Measure Participants | 335 | 168 |
| TEAE |
319
94.7%
|
151
88.8%
|
| TESAE |
143
42.4%
|
70
41.2%
|
| Title | Overall Response Rate (ORR) |
|---|---|
| Description | 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. |
| Time Frame | From the date of randomization to the cut-off date (maximum duration: up to approximately 46 months), assessed every 8 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on tumor response (TR) population that included participants in the ITT population that met 2 criteria: had measurable disease (at least 1 target lesion) at baseline; had at least 1 post-baseline evaluation or early disease progression/cancer-related death occurred before first evaluation on treatment (post-baseline). |
| Arm/Group Title | TAS-102+BSC | Placebo+BSC |
|---|---|---|
| Arm/Group Description | Participants received 35 mg/m^2 of 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 a discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met. | 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. |
| Measure Participants | 290 | 145 |
| Number (95% Confidence Interval) [percentage of participants] |
4.5
1.3%
|
2.1
1.2%
|
| Title | Disease Control Rate (DCR) |
|---|---|
| Description | 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). |
| Time Frame | From the date of randomization to the cut-off date (maximum duration: up to approximately 46 months), assessed every 8 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on TR population that included participants in the ITT population that met 2 criteria: had measurable disease (at least 1 target lesion) at baseline; had at least 1 post-baseline evaluation or early disease progression/cancer-related death occurred before first evaluation on treatment (post-baseline). |
| Arm/Group Title | TAS-102+BSC | Placebo+BSC |
|---|---|---|
| Arm/Group Description | Participants received 35 mg/m^2 of 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 a discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met. | 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. |
| Measure Participants | 290 | 145 |
| Number (95% Confidence Interval) [percentage of participants] |
44.1
13.1%
|
14.5
8.5%
|
| Title | Time to Deterioration of European Cooperative Oncology Group (ECOG) Performance Status Score From Baseline |
|---|---|
| Description | 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. |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on the ITT population that included all randomized participants, regardless of whether or not study treatment was administered. |
| Arm/Group Title | TAS-102+BSC | Placebo+BSC |
|---|---|---|
| Arm/Group Description | Participants received 35 mg/m^2 of 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 a discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met. | 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. |
| Measure Participants | 337 | 170 |
| Median (95% Confidence Interval) [months] |
4.3
|
2.3
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on the ITT population that included all randomized participants, regardless of whether or not study treatment was administered. Here, 'number analyzed' = participants with available data for each specified category. |
| Arm/Group Title | TAS-102+BSC | Placebo+BSC |
|---|---|---|
| Arm/Group Description | Participants received 35 mg/m^2 of 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 a discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met. | 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. |
| Measure Participants | 337 | 170 |
| Cycle 1 |
-2.7
(17.56)
|
-5.9
(22.20)
|
| Cycle 2 |
-5.9
(20.51)
|
-7.3
(25.80)
|
| Cycle 3 |
-4.1
(18.26)
|
-1.4
(22.00)
|
| Cycle 4 |
-3.6
(17.54)
|
-1.7
(22.32)
|
| Cycle 5 |
-5.9
(18.05)
|
11.1
(18.16)
|
| Cycle 6 |
-8.8
(23.05)
|
15.6
(21.10)
|
| Cycle 7 |
-9.5
(21.96)
|
20.0
(4.56)
|
| Cycle 8 |
-4.3
(23.82)
|
16.7
(11.79)
|
| Cycle 9 |
2.4
(17.12)
|
16.7
(16.67)
|
| Cycle 10 |
-14.4
(25.57)
|
25.0
(11.79)
|
| Cycle 11 |
-16.7
(37.27)
|
25.0
(11.79)
|
| Cycle 12 |
-8.3
(11.79)
|
33.3
|
| Cycle 13 |
0.0
|
33.3
|
| Cycle 14 |
33.3
|
|
| Cycle 15 |
33.3
|
|
| Last Collection Cycle |
-8.8
(20.91)
|
-9.8
(25.34)
|
| Safety Follow-Up |
-16.5
(23.45)
|
-8.9
(18.33)
|
| Title | EORTC Quality of Life Questionnaire - Gastric-specific Module (EORTC QLQ-STO22): Percentage of Participants With Overall Compliance |
|---|---|
| Description | 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. |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on the ITT population that included all randomized participants, regardless of whether or not study treatment was administered. |
| Arm/Group Title | TAS-102+BSC | Placebo+BSC |
|---|---|---|
| Arm/Group Description | Participants received 35 mg/m^2 of 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 a discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met. | 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. |
| Measure Participants | 337 | 170 |
| Dysphagia |
86.6
25.7%
|
78.2
46%
|
| Dietary Restrictions |
86.6
25.7%
|
78.2
46%
|
| Pain QS22 |
86.6
25.7%
|
78.2
46%
|
| Reflux |
86.6
25.7%
|
78.2
46%
|
| Anxiety |
86.6
25.7%
|
78.2
46%
|
| Dry Mouth |
86.4
25.6%
|
78.2
46%
|
| Body Image |
85.8
25.5%
|
78.2
46%
|
| Hair Loss |
86.6
25.7%
|
78.2
46%
|
| Taste Problems |
86.6
25.7%
|
78.2
46%
|
Adverse Events
| Time Frame | From first dose of study treatment up to 30 days of last study treatment (maximum duration: up to approximately 46 months). | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Analysis was performed on the AT population. | |||
| Arm/Group Title | TAS-102+BSC | Placebo+BSC | ||
| Arm/Group Description | Participants received 35 mg/m^2 of 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 a discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met. | 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. | ||
All Cause Mortality |
||||
| TAS-102+BSC | Placebo+BSC | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 252/335 (75.2%) | 141/168 (83.9%) | ||
Serious Adverse Events |
||||
| TAS-102+BSC | Placebo+BSC | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 143/335 (42.7%) | 70/168 (41.7%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 13/335 (3.9%) | 13 | 4/168 (2.4%) | 5 |
| Disseminated intravascular coagulation | 1/335 (0.3%) | 2 | 0/168 (0%) | 0 |
| Febrile neutropenia | 4/335 (1.2%) | 4 | 0/168 (0%) | 0 |
| Neutropenia | 4/335 (1.2%) | 5 | 0/168 (0%) | 0 |
| Pancytopenia | 7/335 (2.1%) | 7 | 0/168 (0%) | 0 |
| Thrombocytopenia | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Cardiac disorders | ||||
| Acute coronary syndrome | 2/335 (0.6%) | 2 | 1/168 (0.6%) | 1 |
| Atrial fibrillation | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Cardio-Respiratory arrest | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Myocardial infarction | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Ear and labyrinth disorders | ||||
| Vertigo | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal distension | 1/335 (0.3%) | 1 | 1/168 (0.6%) | 1 |
| Abdominal pain | 8/335 (2.4%) | 8 | 6/168 (3.6%) | 6 |
| Abdominal pain lower | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Abdominal pain upper | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Ascites | 3/335 (0.9%) | 4 | 7/168 (4.2%) | 7 |
| Constipation | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Diarrhoea | 6/335 (1.8%) | 6 | 0/168 (0%) | 0 |
| Dysphagia | 6/335 (1.8%) | 6 | 2/168 (1.2%) | 2 |
| Gastric haemorrhage | 3/335 (0.9%) | 3 | 3/168 (1.8%) | 3 |
| Gastric stenosis | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Gastric ulcer haemorrhage | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Gastrointestinal haemorrhage | 4/335 (1.2%) | 6 | 1/168 (0.6%) | 1 |
| Gastrointestinal obstruction | 0/335 (0%) | 0 | 1/168 (0.6%) | 2 |
| Haematemesis | 3/335 (0.9%) | 3 | 0/168 (0%) | 0 |
| Ileus | 2/335 (0.6%) | 3 | 1/168 (0.6%) | 1 |
| Intestinal obstruction | 4/335 (1.2%) | 4 | 3/168 (1.8%) | 4 |
| Large intestinal obstruction | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Lower gastrointestinal haemorrhage | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Melaena | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Nausea | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Obstruction gastric | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Oesophageal obstruction | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Oesophageal pain | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Oesophagitis | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Pancreatitis | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Small intestinal obstruction | 3/335 (0.9%) | 3 | 2/168 (1.2%) | 2 |
| Stomatitis | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Subileus | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Ulcerative gastritis | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Upper gastrointestinal haemorrhage | 2/335 (0.6%) | 2 | 2/168 (1.2%) | 2 |
| Vomiting | 9/335 (2.7%) | 9 | 1/168 (0.6%) | 2 |
| General disorders | ||||
| Asthenia | 1/335 (0.3%) | 1 | 3/168 (1.8%) | 3 |
| Disease progression | 1/335 (0.3%) | 1 | 1/168 (0.6%) | 1 |
| Fatigue | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| General physical health deterioration | 21/335 (6.3%) | 25 | 15/168 (8.9%) | 20 |
| Malaise | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Pain | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Performance status decreased | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Pyrexia | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Hepatobiliary disorders | ||||
| Cholangitis | 1/335 (0.3%) | 1 | 1/168 (0.6%) | 1 |
| Cholestasis | 1/335 (0.3%) | 2 | 0/168 (0%) | 0 |
| Hepatic failure | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Hepatitis toxic | 0/335 (0%) | 0 | 1/168 (0.6%) | 2 |
| Jaundice | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Jaundice cholestatic | 1/335 (0.3%) | 1 | 1/168 (0.6%) | 1 |
| Infections and infestations | ||||
| Biliary sepsis | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Cellulitis | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Clostridium difficile colitis | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Clostridium difficile infection | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Escherichia sepsis | 1/335 (0.3%) | 2 | 0/168 (0%) | 0 |
| Infection | 2/335 (0.6%) | 3 | 1/168 (0.6%) | 1 |
| Influenza | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Neutropenic sepsis | 4/335 (1.2%) | 6 | 0/168 (0%) | 0 |
| Peritonitis bacterial | 0/335 (0%) | 0 | 1/168 (0.6%) | 2 |
| Pneumonia | 4/335 (1.2%) | 4 | 2/168 (1.2%) | 2 |
| Salmonellosis | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Sepsis | 1/335 (0.3%) | 1 | 1/168 (0.6%) | 1 |
| Septic shock | 3/335 (0.9%) | 3 | 0/168 (0%) | 0 |
| Typhoid fever | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Upper respiratory tract infection | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Urinary tract infection | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Urosepsis | 1/335 (0.3%) | 1 | 1/168 (0.6%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Accidental overdose | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Clavicle fracture | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Thoracic vertebral fracture | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Investigations | ||||
| Bilirubin conjugated increased | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Blood bilirubin increased | 1/335 (0.3%) | 2 | 0/168 (0%) | 0 |
| Neutrophil count decreased | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| White blood cell count decreased | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Alkalosis hypochloraemic | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Cachexia | 1/335 (0.3%) | 1 | 1/168 (0.6%) | 1 |
| Decreased appetite | 11/335 (3.3%) | 11 | 4/168 (2.4%) | 4 |
| Dehydration | 1/335 (0.3%) | 1 | 1/168 (0.6%) | 1 |
| Failure to thrive | 2/335 (0.6%) | 2 | 1/168 (0.6%) | 1 |
| Hypoalbuminaemia | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Hypoglycaemia | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Hyponatraemia | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 0/335 (0%) | 0 | 3/168 (1.8%) | 3 |
| Joint swelling | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Brain neoplasm | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Cancer pain | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Lymphangiosis carcinomatosa | 1/335 (0.3%) | 2 | 0/168 (0%) | 0 |
| Malignant ascites | 1/335 (0.3%) | 1 | 2/168 (1.2%) | 2 |
| Metastases to central nervous system | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Neoplasm malignant | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Tumour haemorrhage | 2/335 (0.6%) | 2 | 1/168 (0.6%) | 1 |
| Ureteric cancer metastatic | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Nervous system disorders | ||||
| Altered state of consciousness | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Cerebral haemorrhage | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Cerebral infarction | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Cerebrovascular accident | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Depressed level of consciousness | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Headache | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Hemiparesis | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Ischaemic stroke | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Presyncope | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Transient ischaemic attack | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Hydronephrosis | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Renal failure | 1/335 (0.3%) | 1 | 1/168 (0.6%) | 1 |
| Reproductive system and breast disorders | ||||
| Breast pain | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Endometrial hyperplasia | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 4/335 (1.2%) | 4 | 2/168 (1.2%) | 2 |
| Pleural effusion | 5/335 (1.5%) | 6 | 1/168 (0.6%) | 1 |
| Pneumonia aspiration | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Pulmonary embolism | 5/335 (1.5%) | 5 | 2/168 (1.2%) | 2 |
| Respiratory failure | 1/335 (0.3%) | 2 | 0/168 (0%) | 0 |
| Vascular disorders | ||||
| Hypotension | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Lymphoedema | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Shock haemorrhagic | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Venous thrombosis | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| TAS-102+BSC | Placebo+BSC | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 319/335 (95.2%) | 151/168 (89.9%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 142/335 (42.4%) | 249 | 30/168 (17.9%) | 52 |
| Bone marrow failure | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Disseminated intravascular coagulation | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Febrile neutropenia | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Leukopenia | 57/335 (17%) | 116 | 3/168 (1.8%) | 14 |
| Lymph node pain | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Lymphadenopathy | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Lymphopenia | 20/335 (6%) | 42 | 8/168 (4.8%) | 21 |
| Neutropenia | 128/335 (38.2%) | 312 | 6/168 (3.6%) | 9 |
| Neutrophilia | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Pancytopenia | 1/335 (0.3%) | 3 | 0/168 (0%) | 0 |
| Thrombocytopenia | 32/335 (9.6%) | 45 | 2/168 (1.2%) | 2 |
| Cardiac disorders | ||||
| Angina pectoris | 1/335 (0.3%) | 1 | 1/168 (0.6%) | 1 |
| Atrial flutter | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Atrial tachycardia | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Bradycardia | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Cardiac disorder | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Cardiovascular insufficiency | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Mitral valve incompetence | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Palpitations | 6/335 (1.8%) | 6 | 2/168 (1.2%) | 2 |
| Pericardial effusion | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Sinus tachycardia | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Tachycardia | 2/335 (0.6%) | 3 | 2/168 (1.2%) | 2 |
| Congenital, familial and genetic disorders | ||||
| Hydrocele | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Ear and labyrinth disorders | ||||
| Ear discomfort | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Ear pain | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Vertigo | 3/335 (0.9%) | 3 | 1/168 (0.6%) | 1 |
| Eye disorders | ||||
| Dry eye | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Eye irritation | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Eye pain | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Eye pruritus | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Lacrimation increased | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Visual impairment | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal discomfort | 3/335 (0.9%) | 4 | 1/168 (0.6%) | 1 |
| Abdominal distension | 13/335 (3.9%) | 15 | 9/168 (5.4%) | 9 |
| Abdominal pain | 50/335 (14.9%) | 75 | 27/168 (16.1%) | 34 |
| Abdominal pain lower | 3/335 (0.9%) | 3 | 2/168 (1.2%) | 2 |
| Abdominal pain upper | 22/335 (6.6%) | 27 | 14/168 (8.3%) | 15 |
| Anal inflammation | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Anal pruritus | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Aphthous ulcer | 1/335 (0.3%) | 2 | 0/168 (0%) | 0 |
| Ascites | 16/335 (4.8%) | 24 | 10/168 (6%) | 18 |
| Cheilitis | 1/335 (0.3%) | 1 | 1/168 (0.6%) | 1 |
| Constipation | 44/335 (13.1%) | 53 | 25/168 (14.9%) | 31 |
| Diarrhoea | 73/335 (21.8%) | 118 | 24/168 (14.3%) | 28 |
| Dry mouth | 3/335 (0.9%) | 3 | 4/168 (2.4%) | 4 |
| Dyschezia | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Dyspepsia | 5/335 (1.5%) | 7 | 3/168 (1.8%) | 4 |
| Dysphagia | 14/335 (4.2%) | 16 | 6/168 (3.6%) | 6 |
| Epigastric discomfort | 1/335 (0.3%) | 1 | 1/168 (0.6%) | 1 |
| Eructation | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Faeces discoloured | 1/335 (0.3%) | 1 | 2/168 (1.2%) | 2 |
| Flatulence | 2/335 (0.6%) | 4 | 2/168 (1.2%) | 2 |
| Gastric haemorrhage | 0/335 (0%) | 0 | 2/168 (1.2%) | 2 |
| Gastric stenosis | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Gastrointestinal haemorrhage | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Gastrooesophageal reflux disease | 4/335 (1.2%) | 5 | 2/168 (1.2%) | 2 |
| Haematemesis | 3/335 (0.9%) | 4 | 0/168 (0%) | 0 |
| Haematochezia | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Haemorrhoidal haemorrhage | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Haemorrhoids | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Ileus | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Impaired gastric emptying | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Intestinal obstruction | 1/335 (0.3%) | 1 | 1/168 (0.6%) | 1 |
| Intra-Abdominal fluid collection | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Lower gastrointestinal haemorrhage | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Melaena | 3/335 (0.9%) | 3 | 0/168 (0%) | 0 |
| Mouth haemorrhage | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Nausea | 123/335 (36.7%) | 201 | 53/168 (31.5%) | 64 |
| Obstruction gastric | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Odynophagia | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Oesophageal pain | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Proctalgia | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Rectal haemorrhage | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Small intestinal obstruction | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Stomatitis | 15/335 (4.5%) | 17 | 3/168 (1.8%) | 3 |
| Toothache | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Upper gastrointestinal haemorrhage | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Vomiting | 80/335 (23.9%) | 104 | 34/168 (20.2%) | 48 |
| General disorders | ||||
| Asthenia | 65/335 (19.4%) | 97 | 37/168 (22%) | 45 |
| Catheter site pain | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Chest discomfort | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Chest pain | 3/335 (0.9%) | 3 | 1/168 (0.6%) | 1 |
| Chills | 4/335 (1.2%) | 6 | 0/168 (0%) | 0 |
| Drug intolerance | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Early satiety | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Face oedema | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Facial pain | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Fatigue | 87/335 (26%) | 136 | 35/168 (20.8%) | 41 |
| Feeling abnormal | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Feeling cold | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Feeling hot | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Gait disturbance | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| General physical health deterioration | 3/335 (0.9%) | 3 | 3/168 (1.8%) | 4 |
| Hyperthermia | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Hypothermia | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Localised oedema | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Malaise | 9/335 (2.7%) | 16 | 8/168 (4.8%) | 8 |
| Mucosal inflammation | 8/335 (2.4%) | 11 | 3/168 (1.8%) | 3 |
| Non-Cardiac chest pain | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Oedema | 8/335 (2.4%) | 8 | 2/168 (1.2%) | 2 |
| Oedema peripheral | 17/335 (5.1%) | 17 | 12/168 (7.1%) | 12 |
| Pain | 5/335 (1.5%) | 6 | 8/168 (4.8%) | 8 |
| Performance status decreased | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Peripheral swelling | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Pyrexia | 23/335 (6.9%) | 37 | 8/168 (4.8%) | 9 |
| Hepatobiliary disorders | ||||
| Biliary colic | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Cholecystitis acute | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Hepatic failure | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Hepatic function abnormal | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Hepatic pain | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Hepatomegaly | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Hyperbilirubinaemia | 10/335 (3%) | 10 | 3/168 (1.8%) | 5 |
| Hypertransaminasaemia | 1/335 (0.3%) | 2 | 0/168 (0%) | 0 |
| Jaundice | 2/335 (0.6%) | 2 | 2/168 (1.2%) | 2 |
| Liver disorder | 4/335 (1.2%) | 6 | 0/168 (0%) | 0 |
| Portal vein thrombosis | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Immune system disorders | ||||
| Autoimmune disorder | 0/335 (0%) | 0 | 1/168 (0.6%) | 2 |
| Perfume sensitivity | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Infections and infestations | ||||
| Angular cheilitis | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Bacterial infection | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Bronchitis | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Candida infection | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Cellulitis | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Clostridium difficile infection | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Conjunctivitis | 3/335 (0.9%) | 3 | 0/168 (0%) | 0 |
| Cystitis | 3/335 (0.9%) | 4 | 0/168 (0%) | 0 |
| Erysipelas | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Gastrointestinal infection | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Gingival abscess | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Gingivitis | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Herpes virus infection | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Herpes zoster | 2/335 (0.6%) | 2 | 1/168 (0.6%) | 1 |
| Influenza | 1/335 (0.3%) | 1 | 1/168 (0.6%) | 1 |
| Laryngitis | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Localised infection | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Lower respiratory tract infection | 3/335 (0.9%) | 4 | 0/168 (0%) | 0 |
| Lung infection | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Nasopharyngitis | 5/335 (1.5%) | 5 | 0/168 (0%) | 0 |
| Oesophageal candidiasis | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Oral candidiasis | 6/335 (1.8%) | 6 | 2/168 (1.2%) | 2 |
| Pneumonia | 4/335 (1.2%) | 4 | 1/168 (0.6%) | 1 |
| Pyuria | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Respiratory tract infection | 3/335 (0.9%) | 3 | 2/168 (1.2%) | 2 |
| Rhinitis | 3/335 (0.9%) | 3 | 0/168 (0%) | 0 |
| Sinusitis | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Skin infection | 1/335 (0.3%) | 1 | 1/168 (0.6%) | 1 |
| Staphylococcal infection | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Tonsillitis | 2/335 (0.6%) | 3 | 0/168 (0%) | 0 |
| Tracheobronchitis | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Upper respiratory tract infection | 8/335 (2.4%) | 9 | 0/168 (0%) | 0 |
| Urinary tract infection | 9/335 (2.7%) | 15 | 4/168 (2.4%) | 4 |
| Urinary tract infection bacterial | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Vulvovaginal candidiasis | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Accidental overdose | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Fall | 3/335 (0.9%) | 3 | 3/168 (1.8%) | 4 |
| Foreign body in gastrointestinal tract | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Procedural pain | 1/335 (0.3%) | 1 | 1/168 (0.6%) | 1 |
| Radiation injury | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Transfusion reaction | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Investigations | ||||
| Alanine aminotransferase | 1/335 (0.3%) | 1 | 1/168 (0.6%) | 1 |
| Alanine aminotransferase increased | 16/335 (4.8%) | 17 | 8/168 (4.8%) | 8 |
| Aspartate aminotransferase | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Aspartate aminotransferase increased | 21/335 (6.3%) | 26 | 13/168 (7.7%) | 15 |
| Bilirubin conjugated increased | 1/335 (0.3%) | 2 | 1/168 (0.6%) | 1 |
| Blood alkaline phosphatase | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Blood alkaline phosphatase increased | 30/335 (9%) | 35 | 14/168 (8.3%) | 15 |
| Blood bilirubin | 1/335 (0.3%) | 3 | 0/168 (0%) | 0 |
| Blood bilirubin increased | 17/335 (5.1%) | 27 | 7/168 (4.2%) | 9 |
| Blood bilirubin unconjugated increased | 1/335 (0.3%) | 2 | 1/168 (0.6%) | 1 |
| Blood creatinine decreased | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Blood creatinine increased | 10/335 (3%) | 11 | 6/168 (3.6%) | 11 |
| Blood iron decreased | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Blood potassium increased | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Blood urea increased | 7/335 (2.1%) | 9 | 7/168 (4.2%) | 8 |
| Creatinine renal clearance decreased | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Enzyme level increased | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Gamma-Glutamyltransferase increased | 4/335 (1.2%) | 6 | 5/168 (3%) | 6 |
| Haematocrit decreased | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Haemoglobin decreased | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Hepatic enzyme increased | 3/335 (0.9%) | 4 | 0/168 (0%) | 0 |
| International normalised ratio increased | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Liver function test increased | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Lymphocyte count decreased | 2/335 (0.6%) | 7 | 0/168 (0%) | 0 |
| Neutrophil count | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Neutrophil count decreased | 50/335 (14.9%) | 139 | 1/168 (0.6%) | 1 |
| Platelet count decreased | 28/335 (8.4%) | 43 | 6/168 (3.6%) | 11 |
| Platelet count increased | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Protein total decreased | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Red blood cell count decreased | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Red cell distribution width increased | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Vital capacity abnormal | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Weight decreased | 20/335 (6%) | 21 | 12/168 (7.1%) | 13 |
| Weight increased | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| White blood cell count decreased | 23/335 (6.9%) | 59 | 0/168 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Cachexia | 3/335 (0.9%) | 3 | 1/168 (0.6%) | 1 |
| Decreased appetite | 109/335 (32.5%) | 164 | 49/168 (29.2%) | 54 |
| Dehydration | 4/335 (1.2%) | 6 | 2/168 (1.2%) | 2 |
| Electrolyte imbalance | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Feeding intolerance | 1/335 (0.3%) | 2 | 0/168 (0%) | 0 |
| Hypercalcaemia | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Hypercreatininaemia | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Hyperglycaemia | 9/335 (2.7%) | 10 | 5/168 (3%) | 5 |
| Hyperkalaemia | 1/335 (0.3%) | 3 | 3/168 (1.8%) | 5 |
| Hyperuricaemia | 1/335 (0.3%) | 1 | 1/168 (0.6%) | 1 |
| Hypoalbuminaemia | 21/335 (6.3%) | 28 | 10/168 (6%) | 11 |
| Hypocalcaemia | 9/335 (2.7%) | 11 | 1/168 (0.6%) | 3 |
| Hypokalaemia | 9/335 (2.7%) | 11 | 3/168 (1.8%) | 3 |
| Hypomagnesaemia | 7/335 (2.1%) | 7 | 3/168 (1.8%) | 3 |
| Hyponatraemia | 5/335 (1.5%) | 6 | 7/168 (4.2%) | 8 |
| Hypophagia | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Hypophosphataemia | 1/335 (0.3%) | 1 | 1/168 (0.6%) | 2 |
| Hypoproteinaemia | 1/335 (0.3%) | 1 | 1/168 (0.6%) | 1 |
| Iron deficiency | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Malnutrition | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Vitamin d deficiency | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 6/335 (1.8%) | 7 | 2/168 (1.2%) | 3 |
| Back pain | 25/335 (7.5%) | 31 | 9/168 (5.4%) | 10 |
| Bone pain | 3/335 (0.9%) | 4 | 0/168 (0%) | 0 |
| Bone swelling | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Flank pain | 1/335 (0.3%) | 1 | 1/168 (0.6%) | 2 |
| Groin pain | 3/335 (0.9%) | 3 | 0/168 (0%) | 0 |
| Intervertebral disc compression | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Intervertebral disc disorder | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Limb discomfort | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Muscle atrophy | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Muscle spasms | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Muscular weakness | 1/335 (0.3%) | 1 | 1/168 (0.6%) | 1 |
| Musculoskeletal chest pain | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Musculoskeletal pain | 5/335 (1.5%) | 6 | 2/168 (1.2%) | 2 |
| Musculoskeletal stiffness | 1/335 (0.3%) | 1 | 1/168 (0.6%) | 1 |
| Myalgia | 4/335 (1.2%) | 5 | 0/168 (0%) | 0 |
| Neck pain | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Osteoarthritis | 1/335 (0.3%) | 1 | 1/168 (0.6%) | 1 |
| Osteoporosis | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Pain in extremity | 3/335 (0.9%) | 5 | 1/168 (0.6%) | 2 |
| Soft tissue disorder | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Spinal pain | 2/335 (0.6%) | 2 | 2/168 (1.2%) | 2 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Cancer pain | 3/335 (0.9%) | 3 | 1/168 (0.6%) | 1 |
| Lipoma | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Malignant ascites | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Skin papilloma | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Tumour associated fever | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Tumour pain | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Nervous system disorders | ||||
| Agnosia | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Amnesia | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Burning sensation | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Dizziness | 8/335 (2.4%) | 10 | 4/168 (2.4%) | 4 |
| Dysgeusia | 11/335 (3.3%) | 17 | 1/168 (0.6%) | 1 |
| Encephalopathy | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Headache | 6/335 (1.8%) | 8 | 4/168 (2.4%) | 5 |
| Lethargy | 2/335 (0.6%) | 2 | 3/168 (1.8%) | 3 |
| Monoplegia | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Myoclonus | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Neuralgia | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Neuropathy peripheral | 4/335 (1.2%) | 4 | 1/168 (0.6%) | 1 |
| Paraesthesia | 8/335 (2.4%) | 8 | 0/168 (0%) | 0 |
| Peripheral sensory neuropathy | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Peroneal nerve palsy | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Sciatica | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Somnolence | 5/335 (1.5%) | 5 | 1/168 (0.6%) | 1 |
| Transient ischaemic attack | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Product Issues | ||||
| Device dislocation | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Psychiatric disorders | ||||
| Agitation | 2/335 (0.6%) | 2 | 2/168 (1.2%) | 2 |
| Anxiety | 9/335 (2.7%) | 9 | 4/168 (2.4%) | 4 |
| Confusional state | 2/335 (0.6%) | 3 | 3/168 (1.8%) | 3 |
| Delirium | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Depression | 3/335 (0.9%) | 5 | 2/168 (1.2%) | 2 |
| Disturbance in social behaviour | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Drug abuse | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Hallucination | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Insomnia | 11/335 (3.3%) | 12 | 10/168 (6%) | 10 |
| Nervousness | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 2/335 (0.6%) | 4 | 1/168 (0.6%) | 1 |
| Albuminuria | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Choluria | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Dysuria | 5/335 (1.5%) | 5 | 3/168 (1.8%) | 3 |
| Haematuria | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Hydronephrosis | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Leukocyturia | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Microalbuminuria | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Micturition disorder | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Nocturia | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Pollakiuria | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Proteinuria | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Renal colic | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Renal pain | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Urinary incontinence | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Urinary retention | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Reproductive system and breast disorders | ||||
| Breast pain | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Endometrial hyperplasia | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Pelvic discomfort | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Pelvic pain | 1/335 (0.3%) | 1 | 2/168 (1.2%) | 2 |
| Vaginal haemorrhage | 0/335 (0%) | 0 | 3/168 (1.8%) | 3 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 11/335 (3.3%) | 12 | 6/168 (3.6%) | 7 |
| Dysphonia | 3/335 (0.9%) | 3 | 0/168 (0%) | 0 |
| Dyspnoea | 21/335 (6.3%) | 24 | 16/168 (9.5%) | 16 |
| Dyspnoea exertional | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Epistaxis | 4/335 (1.2%) | 5 | 1/168 (0.6%) | 1 |
| Hiccups | 4/335 (1.2%) | 4 | 5/168 (3%) | 5 |
| Nasal congestion | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Oropharyngeal pain | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Pleural effusion | 10/335 (3%) | 11 | 4/168 (2.4%) | 4 |
| Pleurisy | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Pleuritic pain | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Pneumonia aspiration | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Productive cough | 4/335 (1.2%) | 4 | 1/168 (0.6%) | 1 |
| Pulmonary embolism | 5/335 (1.5%) | 5 | 1/168 (0.6%) | 1 |
| Respiratory disorder | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Rhinitis allergic | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Rhinorrhoea | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Sputum discoloured | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Tachypnoea | 0/335 (0%) | 0 | 2/168 (1.2%) | 2 |
| Upper respiratory tract inflammation | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Wheezing | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Acne | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Alopecia | 12/335 (3.6%) | 14 | 1/168 (0.6%) | 1 |
| Blister | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Decubitus ulcer | 2/335 (0.6%) | 2 | 1/168 (0.6%) | 1 |
| Dermatitis | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Dermatitis allergic | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Dry skin | 5/335 (1.5%) | 5 | 1/168 (0.6%) | 1 |
| Hand dermatitis | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Hyperhidrosis | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Nail discolouration | 0/335 (0%) | 0 | 1/168 (0.6%) | 1 |
| Nail disorder | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Night sweats | 3/335 (0.9%) | 3 | 0/168 (0%) | 0 |
| Onychoclasis | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Palmar-Plantar erythrodysaesthesia syndrome | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Petechiae | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Pruritus | 8/335 (2.4%) | 9 | 2/168 (1.2%) | 2 |
| Rash | 4/335 (1.2%) | 5 | 1/168 (0.6%) | 1 |
| Rash maculo-papular | 0/335 (0%) | 0 | 1/168 (0.6%) | 4 |
| Skin lesion | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Urticaria | 1/335 (0.3%) | 1 | 1/168 (0.6%) | 1 |
| Xeroderma | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Vascular disorders | ||||
| Deep vein thrombosis | 2/335 (0.6%) | 2 | 1/168 (0.6%) | 1 |
| Embolism | 2/335 (0.6%) | 2 | 0/168 (0%) | 0 |
| Hot flush | 0/335 (0%) | 0 | 2/168 (1.2%) | 2 |
| Hypertension | 3/335 (0.9%) | 3 | 0/168 (0%) | 0 |
| Hypotension | 7/335 (2.1%) | 7 | 1/168 (0.6%) | 1 |
| Pallor | 2/335 (0.6%) | 4 | 0/168 (0%) | 0 |
| Phlebitis | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Raynaud's phenomenon | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
| Thrombophlebitis | 1/335 (0.3%) | 1 | 0/168 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Taiho Central |
|---|---|
| Organization | Taiho Oncology, Inc. |
| Phone | 609-250-7336 |
| clinicaltrialinfo@taihooncology.com |
Responsible Party:
Taiho Oncology, Inc.
ClinicalTrials.gov Identifier:
NCT02500043
Other Study ID Numbers:
- TO-TAS-102-302
- 2015-002683-16
First Posted:
Jul 16, 2015
Last Update Posted:
Sep 16, 2021
Last Verified:
Aug 1, 2021