Phase II Study of FTD/TPI (Lonsurf) in Metastatic Breast Cancers With or Without Prior Exposure to Fluoropyrimidines (LONBRECA)

September 21, 2025 updated by: National University Hospital, Singapore
This is a single arm, open-label, lead in phase Ib dose confirmation, followed by phase II study with 2 parallel study cohorts.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Phase Ib Patients will be treated with twice-daily dosing of FTD/TPI in a 3+3 dose escalation design Phase II

Oral FTD/TPI at RP2D will be administered until disease progression, intolerable toxicity or patient withdrawal.

2 parallel cohorts of patients will be enrolled : Cohort A : patients with prior exposure to fluoropyrimidines Cohort B : patients without prior exposure to fluoropyrimidines

Study Type

Interventional

Enrollment (Estimated)

86

Phase

  • 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 Locations

  • Singapore
      • Singapore, Singapore
        • National University Hospital

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

Ages Eligible for Study

21 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥ 21 years.
  • Histological or cytological diagnosis of breast carcinoma.
  • ECOG 0-2.
  • HER2 negative tumor (IHC 0 -1+ or IHC 2+ and confirmed on HER2 FISH to be negative based on histological report).
  • Patients with HER2 positive tumor may be enrolled if they have failed at least two lines of anti-HER2 based therapies in the metastatic setting, or are intolerant to trastuzumab
  • Any hormone receptor status.
  • Any number of lines of prior palliative endocrine therapy for patients with hormone receptor positive cancer.
  • Has measureable or evaluable disease based on RECIST 1.1 criteria
  • Estimated life expectancy of at least 12 weeks.
  • Has documented progressive disease from last line of therapy.
  • Has recovered from acute toxicities from prior anti-cancer therapies
  • Adequate organ function including the following:

oBone marrow: (I) Absolute neutrophil (segmented and bands) count (ANC) ≥1.5 x 109/L (ii) Platelets ≥100 x 109/L (ii) Hemoglobin ≥8 x 109/L oHepatic: (I)Bilirubin ≤ 1.5 x upper limit of normal (ULN), (ii)ALT or AST ≤ 2.5x ULN, (or ≤ 5 X with liver metastases) oRenal: (I) Creatinine ≤1.5x ULN

  • Signed informed consent from patient or legal representative.
  • Able to comply with study-related procedures.

  • Prior therapy (patients enrolled in phase Ib may be enrolled if they fulfil prior therapy criteria for either Cohort A or Cohort B)

    • Cohort A only: Has received at least 2 lines of palliative systemic therapy, including prior fluropyrimidines (capecitabine, TS-1 or 5-fluorouracil) in the palliative setting, or in the adjuvant setting; patients who have only prior exposure to adjuvant fluoropyrimidines must have relapsed within 12 months of completing adjuvant fluoropyrimidines
    • Cohort B only: Any number of prior lines of palliative chemotherapy and has not received fluoropyrimidines (capecitabine, TS-1 or 5-fluorouracil) in the palliative setting or in the adjuvant setting; patients who have prior exposure to adjuvant fluoropyrimidines are eligible if they have relapsed 12 months from completion of adjuvant fluoropyrimidines.

Exclusion Criteria:

  • Treatment within the last 30 days with any investigational drug.
  • Concurrent administration of any other tumour therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy.
  • Major surgery within 28 days of study drug administration.
  • Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
  • Pregnancy.
  • Breast feeding.
  • Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.
  • Active bleeding disorder or bleeding site.
  • Non-healing wound.
  • Poorly controlled diabetes mellitus.
  • Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.
  • Symptomatic brain metastasis.
  • History of significant neurological or mental disorder, including seizures or dementia.
  • Unable to comply with study procedures

Phase Ib lead-in can recruit patients who fulfil criteria for either Cohort A or Cohort B AND all other inclusion/exclusion criteria

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort A
Patients with prior exposure to fluoropyrimidines
Drug: Cohort A
Oral FTD/TPI at RP2D will be administered until disease progression, intolerable toxicity or patient withdrawal.
Other Names:
  • trifluridine/tipiracil
  • TAS-102 [Lonsurf]
Experimental: Cohort B
Patients without prior exposure to fluoropyrimidines
Drug: Cohort B
Oral FTD/TPI at RP2D will be administered until disease progression, intolerable toxicity or patient withdrawal.
Other Names:
  • trifluridine/tipiracil
  • TAS-102 [Lonsurf]

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: 4 months
Primary endpoint is proportion of patients who are PFS at 4 months in Cohort A
4 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response
Time Frame: 5 years
The death of any patient in the trial from any cause will be recorded and the amount of time from enrollment in the trial until death will be recorded in weeks.
5 years
Progression Free Survival (PFS)
Time Frame: 6 months
Proportion of patients who are PFS at 6 months in Cohort B
6 months
Safety and Efficacy
Time Frame: 5 years
All adverse events experienced by all patients (in both cohort , RP2D of FTD/TPI in MBC Patients) exposed to Trifluridine/tipiracil will be recorded and graded according to CTCAE version 5.
5 years

Collaborators and Investigators

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

Sponsor

National University Hospital, Singapore

Investigators

  • Principal Investigator: Soo Chin Lee, National University Hospital, Singapore

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

August 14, 2019

Primary Completion (Estimated)

June 1, 2026

Study Completion (Estimated)

June 1, 2026

Study Registration Dates

First Submitted

February 10, 2020

First Submitted That Met QC Criteria

February 19, 2020

First Posted (Actual)

February 21, 2020

Study Record Updates

Last Update Posted (Estimated)

September 23, 2025

Last Update Submitted That Met QC Criteria

September 21, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BR01/02/19

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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