Trifluridine/Tipiracil in Combination With Capecitabine and Bevacizumab in Metastatic Colorectal Cancer Patients. (TriComB)

May 19, 2026 updated by: Gruppo Oncologico del Nord-Ovest

A Phase I/II Study Exploring the Safety and Activity of Trifluridine/Tipiracil in Combination With Capecitabine and Bevacizumab in Metastatic Colorectal Cancer Patients

The aim oh this study is to determine the safety and recommended dose of trifluridine/tipiracil plus capecitabine and bevacizumab combination (part 1, dose escalation phase) and to assess its activity in previously untreated mCRC patients who are deemed not eligible for intensive chemotherapy (part 2, expansion phase).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is an open-label, multicenter, phase 1/2 study evaluating the safety and activity of trifluridine/tipiracil in combination with capecitabine and bevacizumab in mCRC. The first part (Part 1) of the study will consist in a dose-escalation assessment of the safety of the treatment in subjects with previously untreated mCRC deemed not fit for irinotecan- and/or oxaliplatin- based regimens (i. e. FOLFOX/XELOX/FOLFIRI/FOLFOXIRI with or without targeted agents).

The second part (Part 2) will be an open-label phase 2 study with a Fleming's single-stage design to evaluate the ORR of the study treatment at the recommended dose established in the first part of the study in the same patients' population.

Trifluridine/tipiracil, capecitabine and bevacizumab will be administered in 28-days cycles until progressive disease, unacceptable toxicities, or patients' refusal.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
48

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Italy
    • MI
      • Milan, MI, Italy, 20133
        • Fondazione IRCCS Istituto Nazionale Tumori
    • PI
      • Pisa, PI, Italy, 56126
        • Azienda Ospedaliero Universitaria Pisana

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Written informed consent to study procedures.
  • Histologically proven diagnosis of colorectal cancer.
  • Metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease.
  • At least one measurable lesion according to RECIST1.1.
  • Age ≥ 18 years.
  • ECOG PS ≤ 1.
  • Life expectancy of at least 12 weeks.
  • Previous adjuvant fluoropyrimidine-based chemotherapy allowed only if more than 12 months elapsed between the end of adjuvant and first relapse.
  • Availability of archival tumour tissue (primary tumour and metastases or at least one of the two) for biomarker analysis.
  • Availability of blood sample for biomarker analysis.
  • Previously not eligible for a chemotherapy doublet or triplet (oxaliplatin and/or irinotecan-based combination).
  • Neutrophils ≥1.5 x 109/L, Platelets ≥100 x 109/L, Hemoglobin ≥ 9 g/dl.
  • Total bilirubin ≤1.5 fold the upper-normal limits (UNL), AST (SGOT) and/or ALT (SGPT) ≤ 2.5 x UNL (or <5 x UNL in the case of liver metastases), alkaline phosphatase ≤ 2.5 x UNL (or <5 x UNL in case of liver metastases).
  • Creatinine clearance ≥ 50 mL/min or serum creatinine ≤1.5 x UNL.
  • Male subjects with female partners of childbearing potential must be willing to use adequate contraception as approved by the investigator (barrier contraceptive measure or oral contraception).
  • Women of childbearing potential must have a negative blood pregnancy test at the baseline visit. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 months, are surgically sterile, or are sexually inactive.
  • Subjects and their partners must be willing to avoid pregnancy during the trial and until 6 months after the last trial treatment.
  • Will and ability to comply with the protocol.

Exclusion Criteria:

  • Radiotherapy to any site within 4 weeks before the study.
  • Previous treatment with trifluridine/tipiracil, bevacizumab and capecitabine (previous treatment with capecitabine was permitted only in the adjuvant setting and if more than 12 months elapsed between the end of adjuvant and first relapse).
  • Untreated brain metastases or spinal cord compression or primary brain tumors.
  • History or evidence upon physical examination of CNS disease unless adequately treated.
  • Clinical signs of malnutrition.
  • Active uncontrolled infections or other clinically relevant concomitant illness contraindicating chemotherapy administration.
  • Evidence of bleeding diathesis or coagulopathy.
  • Uncontrolled hypertension and prior history of hypertensive crisis or hypertensive encephalopathy.
  • Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication.
  • Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months of study enrolment.
  • Any previous venous thromboembolism ≥ NCI CTCAE Grade 4.
  • History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to the first study treatment.
  • Treatment with any investigational drug within 30 days prior to enrolment or 2 investigational agent half-lives (whichever is longer).
  • Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of localized basal and squamous cell carcinoma or cervical cancer in situ.
  • Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication.
  • Known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs.
  • Any concomitant drugs contraindicated for use with the trial drugs according to the product information of the pharmaceutical companies.
  • Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Sexually active males and females (of childbearing potential) unwilling to practice contraception (barrier contraceptive measure or oral contraception) during the study and until 6 months after the last trial treatment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: trifluridine/tipiracil plus capecitabine and bevacizumab
Drug: Capecitabine

Part 1 • Capecitabine, 1000 mg/sqm orally twice daily on days 1-14 each 28 days

Part 2

• Capecitabine, 1000 mg/sqm orally twice daily on days 1-14 each 28 days

Drug: Bevacizumab

Part 1 • Bevacizumab, 5 mg/kg IV dose over 30 minutes on days 1 and 15 each 28 days

Part 2

• Bevacizumab, 5 mg/kg IV dose over 30 minutes on days 1 and 15 each 28 days

Drug: Trifluridine/Tipiracil

Part 1 • Trifluridine/tipiracil, dose escalation from 25 mg/sqm to 35 mg/sqm orally twice daily on days 15-19 (and days 22-26) each 28 days

Part 2

• Trifluridine/tipiracil, at the recommanded dose established during part 1 orally twice daily on days 15-19 (and days 22-26) each 28 days

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
recommended dose
Time Frame: 2 years
recommended dose of the combination trifluridine/tipiracil plus capecitabine plus bevacizumab
2 years
activity
Time Frame: 3 years
activity of the combination trifluridine/tipiracil plus capecitabine plus bevacizumab in terms of overaal response rate per RECIST v1.1.
3 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
quality of life for cancer patients
Time Frame: 3 years
quality of life as measured by EORTC QLQ-C30 questionnaire.
3 years
quality of life for colorectal cancer patients
Time Frame: 3 years
quality of life as measured by EORTC QLQ-CR29 questionnaire.
3 years
quality of life for dimensions health
Time Frame: 3 years
quality of life as measured by EuroQol EQ-5D questionnaire.
3 years
survival
Time Frame: 3 years
efficacy of the combination trifluridine/tipiracil plus capecitabine plus bevacizumab in terms of progression-free survival and overall survival
3 years

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
bioavailability
Time Frame: 2 years
Absolute and relative bioavailability of the combination trifluridine/tipiracil plus capecitabine plus bevacizumab.
2 years
Steady state concentration
Time Frame: 2 years
Steady state concentration of the combination trifluridine/tipiracil plus capecitabine plus bevacizumab.
2 years
Therapeutic index
Time Frame: 2 years
Therapeutic index of the combination trifluridine/tipiracil plus capecitabine plus bevacizumab.
2 years
Volume of distribution
Time Frame: 2 years
Volume of distribution of the combination trifluridine/tipiracil plus capecitabine plus bevacizumab.
2 years
Half-life
Time Frame: 2 years
Plasma half-life of the combination trifluridine/tipiracil plus capecitabine plus bevacizumab.
2 years
Clearance
Time Frame: 2 years
Clearance of the combination trifluridine/tipiracil plus capecitabine plus bevacizumab.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Gruppo Oncologico del Nord-Ovest

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Chiara Cremolini, MD, PhD, Fondazione GONO

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 25, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 29, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 12, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 21, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 25, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 20, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 19, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2024-513271-41-00

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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