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

NCT ID: NCT04280536

Last Updated: 2025-09-23

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 86 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-14
• Study Completion Date: 2026-06-30

Brief Summary

This is a single arm, open-label, lead in phase Ib dose confirmation, followed by phase II study with 2 parallel study cohorts.

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

Conditions

Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A

Patients with prior exposure to fluoropyrimidines

Group Type: EXPERIMENTAL

Cohort A

Intervention Type: DRUG

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

Cohort B

Patients without prior exposure to fluoropyrimidines

Group Type: EXPERIMENTAL

Cohort B

Intervention Type: DRUG

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

Interventions

Cohort A

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

Intervention Type: DRUG

Cohort B

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

Intervention Type: DRUG

Other Intervention Names

trifluridine/tipiracil; TAS-102 [Lonsurf]; trifluridine/tipiracil; TAS-102 [Lonsurf]

Eligibility Criteria

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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National University Hospital, Singapore

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Soo Chin Lee

Role: PRINCIPAL_INVESTIGATOR

National University Hospital, Singapore

Locations

National University Hospital

Singapore, , Singapore

Countries

Singapore

References

Caswell-Jin JL, Plevritis SK, Tian L, Cadham CJ, Xu C, Stout NK, Sledge GW, Mandelblatt JS, Kurian AW. Change in Survival in Metastatic Breast Cancer with Treatment Advances: Meta-Analysis and Systematic Review. JNCI Cancer Spectr. 2018 Nov;2(4):pky062. doi: 10.1093/jncics/pky062. Epub 2018 Dec 24.

Reference Type: BACKGROUND

PMID: 30627694 (View on PubMed)

Crown J, Dieras V, Kaufmann M, von Minckwitz G, Kaye S, Leonard R, Marty M, Misset JL, Osterwalder B, Piccart M. Chemotherapy for metastatic breast cancer-report of a European expert panel. Lancet Oncol. 2002 Dec;3(12):719-27. doi: 10.1016/s1470-2045(02)00927-0.

Reference Type: BACKGROUND

PMID: 12473512 (View on PubMed)

Other Identifiers

BR01/02/19

Identifier Type: -

Identifier Source: org_study_id