Trial · NCT04737187

Phase III Study of Trifluridine/Tipiracil With and Without Bevacizumab in Refractory Metastatic Colorectal Cancer Patients

NCT04737187, Phase 3, Completed, Taiho Oncology, Inc.; results first posted 2023-12-26

3 sourcestrials-2026-11-12-0.4.0

Cite this record

ConductScience Library. Phase III Study of Trifluridine/Tipiracil With and Without Bevacizumab in Refractory Metastatic Colorectal Cancer Patients. Trials, record NCT04737187. Release trials-2026-11-12-0.4.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT04737187

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Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: Phase III Study of Trifluridine/Tipiracil With and Without Bevacizumab in Refractory Metastatic Colorectal Cancer Patients
NCT number: NCT04737187
Status: Completed
Phases: Phase 3
Enrollment: 492 participants, actual
Lead sponsor: Taiho Oncology, Inc.
Conditions: Refractory Metastatic Colorectal Cancer
Interventions: Trifluridine/Tipiracil, Bevacizumab
First posted: 2021-02-03
Last updated: 2024-09-24
Other registries' IDs: eudract:2020-001976-14
Results first posted: 2023-12-26

Source ClinicalTrials.gov

Registered outcomes13

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	Overall Survival (OS)	From date of randomization to the death due to any cause or cut-off date, whichever comes first (maximum duration: up to 20 months)	Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause. The primary estimand of interest was defined to assess the effect of the randomized treatments on the survival duration in all participants regardless of whether or not intercurrent events had occurred (treatment policy strategy). Analysis was performed using Kaplan- Meier method.
Primary	Survival Probability at 6 Months	From date of randomization until 6 months post treatment	Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause. The primary estimand of interest was defined to assess the effect of the randomized treatments on the survival duration in all participants regardless of whether or not intercurrent events had occurred (treatment policy strategy). Analysis was performed using Kaplan- Meier method. In this outcome measure, data of survival probability at 6 months was reported.
Primary	Survival Probability at 12 Months	From date of randomization until 12 months post treatment	Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause. The primary estimand of interest was defined to assess the effect of the randomized treatments on the survival duration in all participants regardless of whether or not intercurrent events had occurred (treatment policy strategy). Analysis was performed using Kaplan- Meier method. In this outcome measure, data of survival probability at 12 months was reported.
Primary	Survival Probability at 18 Months	From date of randomization until 18 months post treatment	Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause. The primary estimand of interest was defined to assess the effect of the randomized treatments on the survival duration in all participants regardless of whether or not intercurrent events had occurred (treatment policy strategy). Analysis was performed using Kaplan- Meier method. In this outcome measure, data of survival probability at 18 months was reported.
Secondary	Progression Free Survival (PFS)	From randomization to the date of radiological tumour progression or death due to any cause or data cut-off date whichever comes first (i.e., up to 20 months)	PFS was defined as the time elapsed between the date of randomisation and the date of radiological tumour progression as per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) assessed by investigator, or death (from any cause), whichever comes first. Progressive Disease (PD) as per RECIST 1.1: at least a 20 percent (%) increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method.
Secondary	Probability of Participants With Progression Free Survival at 3, 6, 9 and 12 Months	From randomization until 3, 6, 9, and 12 months post treatment	PFS was defined as the time elapsed between the date of randomisation and the date of radiological tumour progression as per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) assessed by investigator, or death (from any cause), whichever comes first. Progressive Disease (PD) as per RECIST 1.1: at least a 20 percent (%) increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method. In this outcome measure, data of PFS at 3 months was reported.
Secondary	Overall Response Rate (ORR)	From the date of randomization to the date of documentation of progression or death due to any cause or data cut-off, whichever occurred first (i.e., up to 20 months)	Objective response was defined as percentage of participants who achieved complete response (CR) or partial response (PR) according to the RECIST version 1.1 and using investigator's tumour assessment. As per RECIST 1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters.
Secondary	Percentage of Participants With Disease Control	From randomization to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (i.e., up to 20 months)	Disease control is defined as percentage of participants who achieved CR or PR, or stable disease (SD) as per RECIST 1.1 and using investigator's tumour assessment from the date of randomization to until disease progression or death due to any cause. As per RECIST 1.1, CR: disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions.
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Events (TESAEs)	From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months)	An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. Serious adverse events (SAEs) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as AEs that developed, worsened or became serious during the TEAE period (time from the first dose of study treatment up to 30 days after the last dose of study treatment). TEAEs included both SAEs and non-SAEs.
Secondary	European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30): Time to Definitive Deterioration of >=10 Points in Sub-scale Scores - Kaplan-Meier Analysis	Date of randomization to first deterioration in QoL score >=10 points or death due to any cause, which ever occurred first (i.e., up to 20 months)	EORTC QLQ-C30: 30 item questionnaires with 5 multi-item functional subscales (physical, role, cognitive, emotional, social functioning), 3 multi-item symptom scales (fatigue, nausea/vomiting, and pain), global health/quality of life (QOL) subscale and 6 single items assessing other cancer related symptoms (dyspnea, sleep disturbance, appetite, diarrhea, constipation and financial impact of cancer). It employed twenty-eight 4-point Likert scales with responses from "not at all" to "very much" and GHS/QoL, scored on scale of 1 (very poor) to 7 (excellent). All scales are transformed from raw scores to linear scales ranging 0 to 100. Higher score for functional \& GHS/QoL = higher level of functioning, \& higher score for symptoms scales = higher symptom burden. Time to definitive \>=10 points deterioration: time from date of randomization to first deterioration in QoL score \>=10 points compared to baseline with no later improvement or death due to any cause. Kaplan-Meier method was used.

1 to 10 of 13Source ClinicalTrials.gov

See all 13 registered outcomes

Outcomes13

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	Overall Survival (OS)	From date of randomization to the death due to any cause or cut-off date, whichever comes first (maximum duration: up to 20 months)	Analysis was performed on FAS population.	months	MEDIAN
PRIMARY	Survival Probability at 6 Months	From date of randomization until 6 months post treatment	Analysis was performed on FAS population.	probability of participants	NUMBER
PRIMARY	Survival Probability at 12 Months	From date of randomization until 12 months post treatment	Analysis was performed on FAS population.	probability of participants	NUMBER
PRIMARY	Survival Probability at 18 Months	From date of randomization until 18 months post treatment	Analysis was performed on FAS population.	probability of participants	NUMBER
SECONDARY	Progression Free Survival (PFS)	From randomization to the date of radiological tumour progression or death due to any cause or data cut-off date whichever comes first (i.e., up to 20 months)	Analysis was performed on FAS population.	months	MEDIAN
SECONDARY	Probability of Participants With Progression Free Survival at 3, 6, 9 and 12 Months	From randomization until 3, 6, 9, and 12 months post treatment	Analysis was performed on FAS population.	probability of participants	NUMBER
SECONDARY	Overall Response Rate (ORR)	From the date of randomization to the date of documentation of progression or death due to any cause or data cut-off, whichever occurred first (i.e., up to 20 months)	Analysis was performed on FAS population.	percentage of participants	NUMBER
SECONDARY	Percentage of Participants With Disease Control	From randomization to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (i.e., up to 20 months)	Analysis was performed on FAS population.	percentage of participants	NUMBER
SECONDARY	Number of Participants With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Events (TESAEs)	From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months)	Analysis was performed on safety set which included all participants who had taken at least one dose of investigational medicinal products and were analyzed according to the treatment they actually received.	Participants	COUNT_OF_PARTICIPANTS
SECONDARY	European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30): Time to Definitive Deterioration of >=10 Points in Sub-scale Scores - Kaplan-Meier Analysis	Date of randomization to first deterioration in QoL score >=10 points or death due to any cause, which ever occurred first (i.e., up to 20 months)	Analysis was performed on FAS population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category.	months	MEDIAN

1 to 10 of 13Source ClinicalTrials.gov

See all 13 outcomes

Results by group112

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Value	Spread	Units
Overall Survival (OS)	Trifluridine/Tipiracil + Bevacizumab	10.78	95% Confidence Interval 9.36 to 11.83	months
Overall Survival (OS)	Trifluridine/Tipiracil	7.46	95% Confidence Interval 6.34 to 8.57	months
Survival Probability at 6 Months	Trifluridine/Tipiracil + Bevacizumab	0.77	95% Confidence Interval 0.72 to 0.82	probability of participants
Survival Probability at 6 Months	Trifluridine/Tipiracil	0.61	95% Confidence Interval 0.55 to 0.67	probability of participants
Survival Probability at 12 Months	Trifluridine/Tipiracil + Bevacizumab	0.43	95% Confidence Interval 0.36 to 0.49	probability of participants
Survival Probability at 12 Months	Trifluridine/Tipiracil	0.30	95% Confidence Interval 0.24 to 0.36	probability of participants
Survival Probability at 18 Months	Trifluridine/Tipiracil + Bevacizumab	0.28	95% Confidence Interval 0.19 to 0.37	probability of participants
Survival Probability at 18 Months	Trifluridine/Tipiracil	0.15	95% Confidence Interval 0.09 to 0.22	probability of participants
Progression Free Survival (PFS)	Trifluridine/Tipiracil + Bevacizumab	5.55	95% Confidence Interval 4.50 to 5.88	months
Progression Free Survival (PFS)	Trifluridine/Tipiracil	2.40	95% Confidence Interval 2.07 to 3.22	months

1 to 10 of 112Source ClinicalTrials.gov

See all 112 results by group

Participant flow6

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
Overall Study	STARTED	Trifluridine/Tipiracil + Bevacizumab	246
Overall Study	STARTED	Trifluridine/Tipiracil	246
Overall Study	COMPLETED	Trifluridine/Tipiracil + Bevacizumab	0
Overall Study	COMPLETED	Trifluridine/Tipiracil	0
Overall Study	NOT COMPLETED	Trifluridine/Tipiracil + Bevacizumab	246
Overall Study	NOT COMPLETED	Trifluridine/Tipiracil	246

Source ClinicalTrials.gov

Adverse events326

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk
other	Neutrophil count decreased	Investigations	Trifluridine/Tipiracil + Bevacizumab	34	246
other	Neutrophil count decreased	Investigations	Trifluridine/Tipiracil	18	246
other	Platelet count decreased	Investigations	Trifluridine/Tipiracil + Bevacizumab	24	246
other	Platelet count decreased	Investigations	Trifluridine/Tipiracil	6	246
other	Alanine aminotransferase increased	Investigations	Trifluridine/Tipiracil + Bevacizumab	20	246
other	Alanine aminotransferase increased	Investigations	Trifluridine/Tipiracil	14	246
other	Aspartate aminotransferase increased	Investigations	Trifluridine/Tipiracil + Bevacizumab	20	246
other	Aspartate aminotransferase increased	Investigations	Trifluridine/Tipiracil	14	246
other	Weight decreased	Investigations	Trifluridine/Tipiracil + Bevacizumab	23	246
other	Weight decreased	Investigations	Trifluridine/Tipiracil	12	246

1 to 10 of 326Source ClinicalTrials.gov

See all 326 adverse events

Adverse event totals6

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	Trifluridine/Tipiracil + Bevacizumab	208	246
Total, all-cause mortality	Trifluridine/Tipiracil	224	246
Total, other adverse events	Trifluridine/Tipiracil + Bevacizumab	241	246
Total, other adverse events	Trifluridine/Tipiracil	241	246
Total, serious adverse events	Trifluridine/Tipiracil + Bevacizumab	66	246
Total, serious adverse events	Trifluridine/Tipiracil	79	246

Source ClinicalTrials.gov

Papers2

The papers the trial lists on ClinicalTrials.gov.

PMID	Listed as	Source
37133585	RESULT	PubMed
38953855	DERIVED	PubMed

Grants0

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

None in this release.

Trial comparisons2

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

Comparison	Source
Trifluridine/Tipiracil + Bevacizumab vs Trifluridine/Tipiracil: deaths from any cause	Trial comparisons
Trifluridine/Tipiracil + Bevacizumab vs Trifluridine/Tipiracil: serious adverse events	Trial comparisons

Tests0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

None in this release.

Data dates

The day each source was copied for this release.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNo license stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

For software

Read this trial from software.

The record and each of its lists are JSON, twenty rows a page. No key.

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