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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02500043
Recruitment Status : Completed
First Posted : July 16, 2015
Results First Posted : September 16, 2021
Last Update Posted : September 16, 2021
Sponsor:
Information provided by (Responsible Party):
Taiho Oncology, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Refractory Metastatic Gastric Cancer
Interventions Drug: TAS-102
Drug: Placebo
Enrollment 507
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 Details 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
Hide 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 [1] 335 168
Completed 0 0
Not Completed 337 170
Reason Not Completed
Randomized, but not Treated             2             2
Ongoing at Date of Cut-Off             19             3
Adverse Event             33             11
Clinical Progression             54             35
Radiological Progression             192             110
Physician's Decision             11             3
Withdrawal by Subject             14             4
Death             11             2
Protocol Deviation             1             0
[1]
All participants who received at least 1 dose of study treatment.
Arm/Group Title TAS-102+BSC Placebo+BSC Total
Hide 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 Number of Baseline Participants 337 170 507
Hide Baseline Analysis Population Description
Analysis was performed on the Intent-to-Treat (ITT) population that included all randomized participants, regardless of whether or not study treatment was administered.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 337 participants 170 participants 507 participants
62.8  (10.78) 62.0  (10.04) 62.5  (10.53)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 337 participants 170 participants 507 participants
Female
85
  25.2%
53
  31.2%
138
  27.2%
Male
252
  74.8%
117
  68.8%
369
  72.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 337 participants 170 participants 507 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
   1.0%
European Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 337 participants 170 participants 507 participants
ECOG Grade 0
123
  36.5%
68
  40.0%
191
  37.7%
ECOG Grade 1
214
  63.5%
102
  60.0%
316
  62.3%
[1]
Measure 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 ranged on the scale from 0-5 (0 equal to [=] normal activity; 1= symptoms but ambulatory; 2= in bed for less than (<) 50 percent (%) of the time; 3= in bed for greater than (>) 50% of the time; 4= 100% bedridden; 5= dead). Time to definitive deterioration in ECOG performance status score from baseline was defined as change from 0, 1 to greater than or equal to (>=2), or from 2 to >=3.
1.Primary Outcome
Title Overall Survival (OS)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 337 170
Median (95% Confidence Interval)
Unit of Measure: months
5.7
(4.8 to 6.2)
3.6
(3.1 to 4.1)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments One-sided P-Value.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.6917
Confidence Interval (2-Sided) 95%
0.5597 to 0.8548
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Progression-Free Survival (PFS)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 337 170
Median (95% Confidence Interval)
Unit of Measure: months
2.0
(1.9 to 2.3)
1.8
(1.7 to 1.9)
Hide 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 [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.5723
Confidence Interval (2-Sided) 95%
0.4674 to 0.7008
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAE)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 335 168
Measure Type: Count of Participants
Unit of Measure: Participants
TEAE
319
  95.2%
151
  89.9%
TESAE
143
  42.7%
70
  41.7%
4.Other Pre-specified Outcome
Title Overall Response Rate (ORR)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 290 145
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
4.5
(2.4 to 7.5)
2.1
(0.4 to 5.9)
5.Other Pre-specified Outcome
Title Disease Control Rate (DCR)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 290 145
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
44.1
(38.3 to 50.1)
14.5
(9.2 to 21.3)
6.Other Pre-specified Outcome
Title Time to Deterioration of European Cooperative Oncology Group (ECOG) Performance Status Score From Baseline
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 337 170
Median (95% Confidence Interval)
Unit of Measure: months
4.3
(3.7 to 4.7)
2.3
(2.0 to 2.8)
7.Other Pre-specified Outcome
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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 337 170
Mean (Standard Deviation)
Unit of Measure: units on a scale
Cycle 1 Number Analyzed 279 participants 127 participants
-2.7  (17.56) -5.9  (22.20)
Cycle 2 Number Analyzed 187 participants 58 participants
-5.9  (20.51) -7.3  (25.80)
Cycle 3 Number Analyzed 121 participants 23 participants
-4.1  (18.26) -1.4  (22.00)
Cycle 4 Number Analyzed 79 participants 15 participants
-3.6  (17.54) -1.7  (22.32)
Cycle 5 Number Analyzed 55 participants 9 participants
-5.9  (18.05) 11.1  (18.16)
Cycle 6 Number Analyzed 36 participants 8 participants
-8.8  (23.05) 15.6  (21.10)
Cycle 7 Number Analyzed 28 participants 5 participants
-9.5  (21.96) 20.0  (4.56)
Cycle 8 Number Analyzed 23 participants 5 participants
-4.3  (23.82) 16.7  (11.79)
Cycle 9 Number Analyzed 14 participants 3 participants
2.4  (17.12) 16.7  (16.67)
Cycle 10 Number Analyzed 11 participants 2 participants
-14.4  (25.57) 25.0  (11.79)
Cycle 11 Number Analyzed 5 participants 2 participants
-16.7  (37.27) 25.0  (11.79)
Cycle 12 Number Analyzed 2 participants 1 participants
-8.3  (11.79) 33.3
Cycle 13 Number Analyzed 1 participants 1 participants
0.0 33.3
Cycle 14 Number Analyzed 0 participants 1 participants
33.3
Cycle 15 Number Analyzed 0 participants 1 participants
33.3
Last Collection Cycle Number Analyzed 283 participants 128 participants
-8.8  (20.91) -9.8  (25.34)
Safety Follow-Up Number Analyzed 39 participants 14 participants
-16.5  (23.45) -8.9  (18.33)
8.Other Pre-specified Outcome
Title EORTC Quality of Life Questionnaire - Gastric-specific Module (EORTC QLQ-STO22): Percentage of Participants With Overall Compliance
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 337 170
Measure Type: Number
Unit of Measure: percentage of participants
Dysphagia 86.6 78.2
Dietary Restrictions 86.6 78.2
Pain QS22 86.6 78.2
Reflux 86.6 78.2
Anxiety 86.6 78.2
Dry Mouth 86.4 78.2
Body Image 85.8 78.2
Hair Loss 86.6 78.2
Taste Problems 86.6 78.2
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
Hide 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 (%) Affected / at Risk (%)
Total   252/335 (75.22%)      141/168 (83.93%)    
Hide Serious Adverse Events
TAS-102+BSC Placebo+BSC
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   143/335 (42.69%)      70/168 (41.67%)    
Blood and lymphatic system disorders     
Anaemia  1  13/335 (3.88%)  13 4/168 (2.38%)  5
Disseminated intravascular coagulation  1  1/335 (0.30%)  2 0/168 (0.00%)  0
Febrile neutropenia  1  4/335 (1.19%)  4 0/168 (0.00%)  0
Neutropenia  1  4/335 (1.19%)  5 0/168 (0.00%)  0
Pancytopenia  1  7/335 (2.09%)  7 0/168 (0.00%)  0
Thrombocytopenia  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Cardiac disorders     
Acute coronary syndrome  1  2/335 (0.60%)  2 1/168 (0.60%)  1
Atrial fibrillation  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Cardio-Respiratory arrest  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Myocardial infarction  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Ear and labyrinth disorders     
Vertigo  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Gastrointestinal disorders     
Abdominal distension  1  1/335 (0.30%)  1 1/168 (0.60%)  1
Abdominal pain  1  8/335 (2.39%)  8 6/168 (3.57%)  6
Abdominal pain lower  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Abdominal pain upper  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Ascites  1  3/335 (0.90%)  4 7/168 (4.17%)  7
Constipation  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Diarrhoea  1  6/335 (1.79%)  6 0/168 (0.00%)  0
Dysphagia  1  6/335 (1.79%)  6 2/168 (1.19%)  2
Gastric haemorrhage  1  3/335 (0.90%)  3 3/168 (1.79%)  3
Gastric stenosis  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Gastric ulcer haemorrhage  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Gastrointestinal haemorrhage  1  4/335 (1.19%)  6 1/168 (0.60%)  1
Gastrointestinal obstruction  1  0/335 (0.00%)  0 1/168 (0.60%)  2
Haematemesis  1  3/335 (0.90%)  3 0/168 (0.00%)  0
Ileus  1  2/335 (0.60%)  3 1/168 (0.60%)  1
Intestinal obstruction  1  4/335 (1.19%)  4 3/168 (1.79%)  4
Large intestinal obstruction  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Lower gastrointestinal haemorrhage  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Melaena  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Nausea  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Obstruction gastric  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Oesophageal obstruction  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Oesophageal pain  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Oesophagitis  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Pancreatitis  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Small intestinal obstruction  1  3/335 (0.90%)  3 2/168 (1.19%)  2
Stomatitis  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Subileus  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Ulcerative gastritis  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Upper gastrointestinal haemorrhage  1  2/335 (0.60%)  2 2/168 (1.19%)  2
Vomiting  1  9/335 (2.69%)  9 1/168 (0.60%)  2
General disorders     
Asthenia  1  1/335 (0.30%)  1 3/168 (1.79%)  3
Disease progression  1  1/335 (0.30%)  1 1/168 (0.60%)  1
Fatigue  1  2/335 (0.60%)  2 0/168 (0.00%)  0
General physical health deterioration  1  21/335 (6.27%)  25 15/168 (8.93%)  20
Malaise  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Pain  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Performance status decreased  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Pyrexia  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Hepatobiliary disorders     
Cholangitis  1  1/335 (0.30%)  1 1/168 (0.60%)  1
Cholestasis  1  1/335 (0.30%)  2 0/168 (0.00%)  0
Hepatic failure  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Hepatitis toxic  1  0/335 (0.00%)  0 1/168 (0.60%)  2
Jaundice  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Jaundice cholestatic  1  1/335 (0.30%)  1 1/168 (0.60%)  1
Infections and infestations     
Biliary sepsis  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Cellulitis  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Clostridium difficile colitis  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Clostridium difficile infection  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Escherichia sepsis  1  1/335 (0.30%)  2 0/168 (0.00%)  0
Infection  1  2/335 (0.60%)  3 1/168 (0.60%)  1
Influenza  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Neutropenic sepsis  1  4/335 (1.19%)  6 0/168 (0.00%)  0
Peritonitis bacterial  1  0/335 (0.00%)  0 1/168 (0.60%)  2
Pneumonia  1  4/335 (1.19%)  4 2/168 (1.19%)  2
Salmonellosis  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Sepsis  1  1/335 (0.30%)  1 1/168 (0.60%)  1
Septic shock  1  3/335 (0.90%)  3 0/168 (0.00%)  0
Typhoid fever  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Upper respiratory tract infection  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Urinary tract infection  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Urosepsis  1  1/335 (0.30%)  1 1/168 (0.60%)  1
Injury, poisoning and procedural complications     
Accidental overdose  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Clavicle fracture  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Thoracic vertebral fracture  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Investigations     
Bilirubin conjugated increased  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Blood bilirubin increased  1  1/335 (0.30%)  2 0/168 (0.00%)  0
Neutrophil count decreased  1  2/335 (0.60%)  2 0/168 (0.00%)  0
White blood cell count decreased  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Metabolism and nutrition disorders     
Alkalosis hypochloraemic  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Cachexia  1  1/335 (0.30%)  1 1/168 (0.60%)  1
Decreased appetite  1  11/335 (3.28%)  11 4/168 (2.38%)  4
Dehydration  1  1/335 (0.30%)  1 1/168 (0.60%)  1
Failure to thrive  1  2/335 (0.60%)  2 1/168 (0.60%)  1
Hypoalbuminaemia  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Hypoglycaemia  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Hyponatraemia  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Musculoskeletal and connective tissue disorders     
Back pain  1  0/335 (0.00%)  0 3/168 (1.79%)  3
Joint swelling  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Brain neoplasm  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Cancer pain  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Lymphangiosis carcinomatosa  1  1/335 (0.30%)  2 0/168 (0.00%)  0
Malignant ascites  1  1/335 (0.30%)  1 2/168 (1.19%)  2
Metastases to central nervous system  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Neoplasm malignant  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Tumour haemorrhage  1  2/335 (0.60%)  2 1/168 (0.60%)  1
Ureteric cancer metastatic  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Nervous system disorders     
Altered state of consciousness  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Cerebral haemorrhage  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Cerebral infarction  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Cerebrovascular accident  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Depressed level of consciousness  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Headache  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Hemiparesis  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Ischaemic stroke  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Presyncope  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Transient ischaemic attack  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Hydronephrosis  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Renal failure  1  1/335 (0.30%)  1 1/168 (0.60%)  1
Reproductive system and breast disorders     
Breast pain  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Endometrial hyperplasia  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  4/335 (1.19%)  4 2/168 (1.19%)  2
Pleural effusion  1  5/335 (1.49%)  6 1/168 (0.60%)  1
Pneumonia aspiration  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Pulmonary embolism  1  5/335 (1.49%)  5 2/168 (1.19%)  2
Respiratory failure  1  1/335 (0.30%)  2 0/168 (0.00%)  0
Vascular disorders     
Hypotension  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Lymphoedema  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Shock haemorrhagic  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Venous thrombosis  1  1/335 (0.30%)  1 0/168 (0.00%)  0
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
TAS-102+BSC Placebo+BSC
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   319/335 (95.22%)      151/168 (89.88%)    
Blood and lymphatic system disorders     
Anaemia  1  142/335 (42.39%)  249 30/168 (17.86%)  52
Bone marrow failure  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Disseminated intravascular coagulation  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Febrile neutropenia  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Leukopenia  1  57/335 (17.01%)  116 3/168 (1.79%)  14
Lymph node pain  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Lymphadenopathy  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Lymphopenia  1  20/335 (5.97%)  42 8/168 (4.76%)  21
Neutropenia  1  128/335 (38.21%)  312 6/168 (3.57%)  9
Neutrophilia  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Pancytopenia  1  1/335 (0.30%)  3 0/168 (0.00%)  0
Thrombocytopenia  1  32/335 (9.55%)  45 2/168 (1.19%)  2
Cardiac disorders     
Angina pectoris  1  1/335 (0.30%)  1 1/168 (0.60%)  1
Atrial flutter  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Atrial tachycardia  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Bradycardia  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Cardiac disorder  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Cardiovascular insufficiency  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Mitral valve incompetence  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Palpitations  1  6/335 (1.79%)  6 2/168 (1.19%)  2
Pericardial effusion  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Sinus tachycardia  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Tachycardia  1  2/335 (0.60%)  3 2/168 (1.19%)  2
Congenital, familial and genetic disorders     
Hydrocele  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Ear and labyrinth disorders     
Ear discomfort  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Ear pain  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Vertigo  1  3/335 (0.90%)  3 1/168 (0.60%)  1
Eye disorders     
Dry eye  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Eye irritation  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Eye pain  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Eye pruritus  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Lacrimation increased  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Visual impairment  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Gastrointestinal disorders     
Abdominal discomfort  1  3/335 (0.90%)  4 1/168 (0.60%)  1
Abdominal distension  1  13/335 (3.88%)  15 9/168 (5.36%)  9
Abdominal pain  1  50/335 (14.93%)  75 27/168 (16.07%)  34
Abdominal pain lower  1  3/335 (0.90%)  3 2/168 (1.19%)  2
Abdominal pain upper  1  22/335 (6.57%)  27 14/168 (8.33%)  15
Anal inflammation  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Anal pruritus  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Aphthous ulcer  1  1/335 (0.30%)  2 0/168 (0.00%)  0
Ascites  1  16/335 (4.78%)  24 10/168 (5.95%)  18
Cheilitis  1  1/335 (0.30%)  1 1/168 (0.60%)  1
Constipation  1  44/335 (13.13%)  53 25/168 (14.88%)  31
Diarrhoea  1  73/335 (21.79%)  118 24/168 (14.29%)  28
Dry mouth  1  3/335 (0.90%)  3 4/168 (2.38%)  4
Dyschezia  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Dyspepsia  1  5/335 (1.49%)  7 3/168 (1.79%)  4
Dysphagia  1  14/335 (4.18%)  16 6/168 (3.57%)  6
Epigastric discomfort  1  1/335 (0.30%)  1 1/168 (0.60%)  1
Eructation  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Faeces discoloured  1  1/335 (0.30%)  1 2/168 (1.19%)  2
Flatulence  1  2/335 (0.60%)  4 2/168 (1.19%)  2
Gastric haemorrhage  1  0/335 (0.00%)  0 2/168 (1.19%)  2
Gastric stenosis  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Gastrointestinal haemorrhage  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Gastrooesophageal reflux disease  1  4/335 (1.19%)  5 2/168 (1.19%)  2
Haematemesis  1  3/335 (0.90%)  4 0/168 (0.00%)  0
Haematochezia  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Haemorrhoidal haemorrhage  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Haemorrhoids  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Ileus  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Impaired gastric emptying  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Intestinal obstruction  1  1/335 (0.30%)  1 1/168 (0.60%)  1
Intra-Abdominal fluid collection  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Lower gastrointestinal haemorrhage  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Melaena  1  3/335 (0.90%)  3 0/168 (0.00%)  0
Mouth haemorrhage  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Nausea  1  123/335 (36.72%)  201 53/168 (31.55%)  64
Obstruction gastric  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Odynophagia  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Oesophageal pain  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Proctalgia  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Rectal haemorrhage  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Small intestinal obstruction  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Stomatitis  1  15/335 (4.48%)  17 3/168 (1.79%)  3
Toothache  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Upper gastrointestinal haemorrhage  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Vomiting  1  80/335 (23.88%)  104 34/168 (20.24%)  48
General disorders     
Asthenia  1  65/335 (19.40%)  97 37/168 (22.02%)  45
Catheter site pain  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Chest discomfort  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Chest pain  1  3/335 (0.90%)  3 1/168 (0.60%)  1
Chills  1  4/335 (1.19%)  6 0/168 (0.00%)  0
Drug intolerance  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Early satiety  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Face oedema  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Facial pain  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Fatigue  1  87/335 (25.97%)  136 35/168 (20.83%)  41
Feeling abnormal  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Feeling cold  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Feeling hot  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Gait disturbance  1  1/335 (0.30%)  1 0/168 (0.00%)  0
General physical health deterioration  1  3/335 (0.90%)  3 3/168 (1.79%)  4
Hyperthermia  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Hypothermia  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Localised oedema  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Malaise  1  9/335 (2.69%)  16 8/168 (4.76%)  8
Mucosal inflammation  1  8/335 (2.39%)  11 3/168 (1.79%)  3
Non-Cardiac chest pain  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Oedema  1  8/335 (2.39%)  8 2/168 (1.19%)  2
Oedema peripheral  1  17/335 (5.07%)  17 12/168 (7.14%)  12
Pain  1  5/335 (1.49%)  6 8/168 (4.76%)  8
Performance status decreased  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Peripheral swelling  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Pyrexia  1  23/335 (6.87%)  37 8/168 (4.76%)  9
Hepatobiliary disorders     
Biliary colic  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Cholecystitis acute  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Hepatic failure  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Hepatic function abnormal  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Hepatic pain  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Hepatomegaly  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Hyperbilirubinaemia  1  10/335 (2.99%)  10 3/168 (1.79%)  5
Hypertransaminasaemia  1  1/335 (0.30%)  2 0/168 (0.00%)  0
Jaundice  1  2/335 (0.60%)  2 2/168 (1.19%)  2
Liver disorder  1  4/335 (1.19%)  6 0/168 (0.00%)  0
Portal vein thrombosis  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Immune system disorders     
Autoimmune disorder  1  0/335 (0.00%)  0 1/168 (0.60%)  2
Perfume sensitivity  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Infections and infestations     
Angular cheilitis  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Bacterial infection  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Bronchitis  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Candida infection  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Cellulitis  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Clostridium difficile infection  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Conjunctivitis  1  3/335 (0.90%)  3 0/168 (0.00%)  0
Cystitis  1  3/335 (0.90%)  4 0/168 (0.00%)  0
Erysipelas  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Gastrointestinal infection  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Gingival abscess  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Gingivitis  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Herpes virus infection  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Herpes zoster  1  2/335 (0.60%)  2 1/168 (0.60%)  1
Influenza  1  1/335 (0.30%)  1 1/168 (0.60%)  1
Laryngitis  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Localised infection  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Lower respiratory tract infection  1  3/335 (0.90%)  4 0/168 (0.00%)  0
Lung infection  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Nasopharyngitis  1  5/335 (1.49%)  5 0/168 (0.00%)  0
Oesophageal candidiasis  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Oral candidiasis  1  6/335 (1.79%)  6 2/168 (1.19%)  2
Pneumonia  1  4/335 (1.19%)  4 1/168 (0.60%)  1
Pyuria  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Respiratory tract infection  1  3/335 (0.90%)  3 2/168 (1.19%)  2
Rhinitis  1  3/335 (0.90%)  3 0/168 (0.00%)  0
Sinusitis  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Skin infection  1  1/335 (0.30%)  1 1/168 (0.60%)  1
Staphylococcal infection  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Tonsillitis  1  2/335 (0.60%)  3 0/168 (0.00%)  0
Tracheobronchitis  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Upper respiratory tract infection  1  8/335 (2.39%)  9 0/168 (0.00%)  0
Urinary tract infection  1  9/335 (2.69%)  15 4/168 (2.38%)  4
Urinary tract infection bacterial  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Vulvovaginal candidiasis  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Injury, poisoning and procedural complications     
Accidental overdose  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Fall  1  3/335 (0.90%)  3 3/168 (1.79%)  4
Foreign body in gastrointestinal tract  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Procedural pain  1  1/335 (0.30%)  1 1/168 (0.60%)  1
Radiation injury  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Transfusion reaction  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Investigations     
Alanine aminotransferase  1  1/335 (0.30%)  1 1/168 (0.60%)  1
Alanine aminotransferase increased  1  16/335 (4.78%)  17 8/168 (4.76%)  8
Aspartate aminotransferase  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Aspartate aminotransferase increased  1  21/335 (6.27%)  26 13/168 (7.74%)  15
Bilirubin conjugated increased  1  1/335 (0.30%)  2 1/168 (0.60%)  1
Blood alkaline phosphatase  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Blood alkaline phosphatase increased  1  30/335 (8.96%)  35 14/168 (8.33%)  15
Blood bilirubin  1  1/335 (0.30%)  3 0/168 (0.00%)  0
Blood bilirubin increased  1  17/335 (5.07%)  27 7/168 (4.17%)  9
Blood bilirubin unconjugated increased  1  1/335 (0.30%)  2 1/168 (0.60%)  1
Blood creatinine decreased  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Blood creatinine increased  1  10/335 (2.99%)  11 6/168 (3.57%)  11
Blood iron decreased  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Blood potassium increased  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Blood urea increased  1  7/335 (2.09%)  9 7/168 (4.17%)  8
Creatinine renal clearance decreased  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Enzyme level increased  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Gamma-Glutamyltransferase increased  1  4/335 (1.19%)  6 5/168 (2.98%)  6
Haematocrit decreased  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Haemoglobin decreased  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Hepatic enzyme increased  1  3/335 (0.90%)  4 0/168 (0.00%)  0
International normalised ratio increased  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Liver function test increased  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Lymphocyte count decreased  1  2/335 (0.60%)  7 0/168 (0.00%)  0
Neutrophil count  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Neutrophil count decreased  1  50/335 (14.93%)  139 1/168 (0.60%)  1
Platelet count decreased  1  28/335 (8.36%)  43 6/168 (3.57%)  11
Platelet count increased  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Protein total decreased  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Red blood cell count decreased  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Red cell distribution width increased  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Vital capacity abnormal  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Weight decreased  1  20/335 (5.97%)  21 12/168 (7.14%)  13
Weight increased  1  0/335 (0.00%)  0 1/168 (0.60%)  1
White blood cell count decreased  1  23/335 (6.87%)  59 0/168 (0.00%)  0
Metabolism and nutrition disorders     
Cachexia  1  3/335 (0.90%)  3 1/168 (0.60%)  1
Decreased appetite  1  109/335 (32.54%)  164 49/168 (29.17%)  54
Dehydration  1  4/335 (1.19%)  6 2/168 (1.19%)  2
Electrolyte imbalance  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Feeding intolerance  1  1/335 (0.30%)  2 0/168 (0.00%)  0
Hypercalcaemia  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Hypercreatininaemia  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Hyperglycaemia  1  9/335 (2.69%)  10 5/168 (2.98%)  5
Hyperkalaemia  1  1/335 (0.30%)  3 3/168 (1.79%)  5
Hyperuricaemia  1  1/335 (0.30%)  1 1/168 (0.60%)  1
Hypoalbuminaemia  1  21/335 (6.27%)  28 10/168 (5.95%)  11
Hypocalcaemia  1  9/335 (2.69%)  11 1/168 (0.60%)  3
Hypokalaemia  1  9/335 (2.69%)  11 3/168 (1.79%)  3
Hypomagnesaemia  1  7/335 (2.09%)  7 3/168 (1.79%)  3
Hyponatraemia  1  5/335 (1.49%)  6 7/168 (4.17%)  8
Hypophagia  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Hypophosphataemia  1  1/335 (0.30%)  1 1/168 (0.60%)  2
Hypoproteinaemia  1  1/335 (0.30%)  1 1/168 (0.60%)  1
Iron deficiency  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Malnutrition  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Vitamin d deficiency  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Arthralgia  1  6/335 (1.79%)  7 2/168 (1.19%)  3
Back pain  1  25/335 (7.46%)  31 9/168 (5.36%)  10
Bone pain  1  3/335 (0.90%)  4 0/168 (0.00%)  0
Bone swelling  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Flank pain  1  1/335 (0.30%)  1 1/168 (0.60%)  2
Groin pain  1  3/335 (0.90%)  3 0/168 (0.00%)  0
Intervertebral disc compression  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Intervertebral disc disorder  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Limb discomfort  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Muscle atrophy  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Muscle spasms  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Muscular weakness  1  1/335 (0.30%)  1 1/168 (0.60%)  1
Musculoskeletal chest pain  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Musculoskeletal pain  1  5/335 (1.49%)  6 2/168 (1.19%)  2
Musculoskeletal stiffness  1  1/335 (0.30%)  1 1/168 (0.60%)  1
Myalgia  1  4/335 (1.19%)  5 0/168 (0.00%)  0
Neck pain  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Osteoarthritis  1  1/335 (0.30%)  1 1/168 (0.60%)  1
Osteoporosis  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Pain in extremity  1  3/335 (0.90%)  5 1/168 (0.60%)  2
Soft tissue disorder  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Spinal pain  1  2/335 (0.60%)  2 2/168 (1.19%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cancer pain  1  3/335 (0.90%)  3 1/168 (0.60%)  1
Lipoma  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Malignant ascites  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Skin papilloma  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Tumour associated fever  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Tumour pain  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Nervous system disorders     
Agnosia  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Amnesia  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Burning sensation  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Dizziness  1  8/335 (2.39%)  10 4/168 (2.38%)  4
Dysgeusia  1  11/335 (3.28%)  17 1/168 (0.60%)  1
Encephalopathy  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Headache  1  6/335 (1.79%)  8 4/168 (2.38%)  5
Lethargy  1  2/335 (0.60%)  2 3/168 (1.79%)  3
Monoplegia  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Myoclonus  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Neuralgia  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Neuropathy peripheral  1  4/335 (1.19%)  4 1/168 (0.60%)  1
Paraesthesia  1  8/335 (2.39%)  8 0/168 (0.00%)  0
Peripheral sensory neuropathy  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Peroneal nerve palsy  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Sciatica  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Somnolence  1  5/335 (1.49%)  5 1/168 (0.60%)  1
Transient ischaemic attack  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Product Issues     
Device dislocation  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Psychiatric disorders     
Agitation  1  2/335 (0.60%)  2 2/168 (1.19%)  2
Anxiety  1  9/335 (2.69%)  9 4/168 (2.38%)  4
Confusional state  1  2/335 (0.60%)  3 3/168 (1.79%)  3
Delirium  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Depression  1  3/335 (0.90%)  5 2/168 (1.19%)  2
Disturbance in social behaviour  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Drug abuse  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Hallucination  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Insomnia  1  11/335 (3.28%)  12 10/168 (5.95%)  10
Nervousness  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury  1  2/335 (0.60%)  4 1/168 (0.60%)  1
Albuminuria  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Choluria  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Dysuria  1  5/335 (1.49%)  5 3/168 (1.79%)  3
Haematuria  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Hydronephrosis  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Leukocyturia  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Microalbuminuria  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Micturition disorder  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Nocturia  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Pollakiuria  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Proteinuria  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Renal colic  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Renal pain  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Urinary incontinence  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Urinary retention  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Reproductive system and breast disorders     
Breast pain  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Endometrial hyperplasia  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Pelvic discomfort  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Pelvic pain  1  1/335 (0.30%)  1 2/168 (1.19%)  2
Vaginal haemorrhage  1  0/335 (0.00%)  0 3/168 (1.79%)  3
Respiratory, thoracic and mediastinal disorders     
Cough  1  11/335 (3.28%)  12 6/168 (3.57%)  7
Dysphonia  1  3/335 (0.90%)  3 0/168 (0.00%)  0
Dyspnoea  1  21/335 (6.27%)  24 16/168 (9.52%)  16
Dyspnoea exertional  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Epistaxis  1  4/335 (1.19%)  5 1/168 (0.60%)  1
Hiccups  1  4/335 (1.19%)  4 5/168 (2.98%)  5
Nasal congestion  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Oropharyngeal pain  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Pleural effusion  1  10/335 (2.99%)  11 4/168 (2.38%)  4
Pleurisy  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Pleuritic pain  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Pneumonia aspiration  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Productive cough  1  4/335 (1.19%)  4 1/168 (0.60%)  1
Pulmonary embolism  1  5/335 (1.49%)  5 1/168 (0.60%)  1
Respiratory disorder  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Rhinitis allergic  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Rhinorrhoea  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Sputum discoloured  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Tachypnoea  1  0/335 (0.00%)  0 2/168 (1.19%)  2
Upper respiratory tract inflammation  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Wheezing  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Skin and subcutaneous tissue disorders     
Acne  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Alopecia  1  12/335 (3.58%)  14 1/168 (0.60%)  1
Blister  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Decubitus ulcer  1  2/335 (0.60%)  2 1/168 (0.60%)  1
Dermatitis  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Dermatitis allergic  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Dry skin  1  5/335 (1.49%)  5 1/168 (0.60%)  1
Hand dermatitis  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Hyperhidrosis  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Nail discolouration  1  0/335 (0.00%)  0 1/168 (0.60%)  1
Nail disorder  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Night sweats  1  3/335 (0.90%)  3 0/168 (0.00%)  0
Onychoclasis  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Palmar-Plantar erythrodysaesthesia syndrome  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Petechiae  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Pruritus  1  8/335 (2.39%)  9 2/168 (1.19%)  2
Rash  1  4/335 (1.19%)  5 1/168 (0.60%)  1
Rash maculo-papular  1  0/335 (0.00%)  0 1/168 (0.60%)  4
Skin lesion  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Urticaria  1  1/335 (0.30%)  1 1/168 (0.60%)  1
Xeroderma  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Vascular disorders     
Deep vein thrombosis  1  2/335 (0.60%)  2 1/168 (0.60%)  1
Embolism  1  2/335 (0.60%)  2 0/168 (0.00%)  0
Hot flush  1  0/335 (0.00%)  0 2/168 (1.19%)  2
Hypertension  1  3/335 (0.90%)  3 0/168 (0.00%)  0
Hypotension  1  7/335 (2.09%)  7 1/168 (0.60%)  1
Pallor  1  2/335 (0.60%)  4 0/168 (0.00%)  0
Phlebitis  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Raynaud's phenomenon  1  1/335 (0.30%)  1 0/168 (0.00%)  0
Thrombophlebitis  1  1/335 (0.30%)  1 0/168 (0.00%)  0
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
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
Layout table for Results Point of Contact information
Name/Title: Taiho Central
Organization: Taiho Oncology, Inc.
Phone: 609-250-7336
EMail: clinicaltrialinfo@taihooncology.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Taiho Oncology, Inc.
ClinicalTrials.gov Identifier: NCT02500043    
Other Study ID Numbers: TO-TAS-102-302
2015-002683-16 ( EudraCT Number )
First Submitted: July 13, 2015
First Posted: July 16, 2015
Results First Submitted: July 2, 2021
Results First Posted: September 16, 2021
Last Update Posted: September 16, 2021