TAS102 in Patients With ER-positive, HER2-negative Advanced Breast Cancer

NCT04489173 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: BOOG 2019-01
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 10

Brief Summary

This is a multicenter phase 2 study evaluating the efficacy and safety of trifluridine/tipiracil in women with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy.

Conditions

Breast Neoplasm; Chemotherapy Effect

Keywords

TAS102

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  Response rate CR/PR

  8 weeks

Secondary Outcomes (2)

• Adverse events

  every 4 weeks

• QoL

  32 weeks

Study Arms (1)

Treatment

EXPERIMENTAL

Treatment with TAS102

Drug: trifluridine/tipiracil

Interventions

trifluridine/tipiracil DRUG

Study medication should be started within 3 days after completion of screening and continue until a study treatment discontinuation criterion is met. Trifluridine/tipiracil will be administered orally BID on days 1 through 5, with the first dose administered in the morning of day 1 of each cycle and the last dose administered in the evening of day 5, followed by a recovery period from day 6 through day 7. Trifluridine/tipiracil will be administered orally BID on days 8 through 12, with the first dose administered in the morning of day 8 of each cycle and the last dose administered in the evening of day 12, followed by a recovery period from day 13 through day 28. Each cycle will be 28 days.

Also known as: Lonsurf, TAS102

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult women(≥ 18 years of age) with proven diagnosis of metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy
• Documented ER positive (10%) and/or PR positive (10%) and HER2 negative metastatic breast cancer
• Progressive disease based on imaging
• Women previously treated with capecitabine (in metastatic setting), and a maximum of two other lines of chemotherapy including a taxane either in the (neo)adjuvant or metastatic setting.
• Evaluable disease as defined per RECIST v.1.1 (see Appendix B). Tumor lesions previously irradiated or subjected to other locoregional therapy will only be deemed measurable if disease progression at the treated site after completion of therapy is clearly documented.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• Life expectancy of ≥ 12 weeks
• Willing and able to comply with scheduled visits and study procedures
• Adequate organ, bone marrow and coagulation function as shown by:
• Absolute neutrophil count (ANC) ≥ 1.5 ×109/L
• Platelets ≥ 75 ×109/L
• Hemoglobin (Hgb) ≥ 5.6 mmol/L
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 ULN (or ≤ 5 if hepatic metastases are present)
• Total serum bilirubin ≤ 1.5 × ULN (≤ 3 × ULN for patients known to have Gilbert Syndrome)
• Creatinine clearance ≥60 ml/min

You may not qualify if:

• HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive) and ER-negative patients are not eligible
• No more than two lines of chemotherapy for advanced disease
• Resolution of side-effects from previous chemotherapy \> grade 1 (except for alopecia)
• Radiotherapy within four weeks prior to enrollment is not allowed except in case of localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture which can then be completed within two weeks prior to enrollment. Patients must have recovered from radiotherapy toxicities prior to enrollment.
• % or more marrow-bearing bone being irradiated. Other primary tumors within the last 5 years before study entry are not allowed, except for adequately controlled basal cell carcinoma of the skin, or carcinoma in situ of the cervix.
• Previous or current CNS metastases, carcinomatous meningitis, are not allowed. A CT or MRI of the brain must be performed within 4 weeks prior to registration if the presence of metastases at this site is suspected.
• Evidence of clinically significant cardiovascular or pulmonary disease or any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, or that may affect patient compliance with study routines, or places the patient at high risk from treatment related complications. (e.g lactose intolerance)
• Previously received trifluridine/tipiracil
• Since trifluridine/tipiracil contains lactose, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine
• Diagnosis of any other malignancy prior to registration, except those that are not believed to influence the patient's prognosis and do not require any further treatment.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Sponsors & Collaborators

• Borstkanker Onderzoek Groep: lead
• Erasmus Medical Center: collaborator
• UMC Utrecht: collaborator
• Servier: collaborator
• BOOG Study Center: collaborator

Study Sites (10)

Rijnstate

Arnhem, Netherlands

Location

Wilhelmina ziekenhuis

Assen, Netherlands

Location

Amphia Ziekenhuis

Breda, Netherlands

Location

Reinier de Graaf Groep

Delft, Netherlands

Location

Deventer ziekenhuis

Deventer, Netherlands

Location

Catharina Ziekenhuis

Eindhoven, Netherlands

Location

MC Leeuwarden

Leeuwarden, Netherlands

Location

MUMC

Maastricht, Netherlands

Location

Erasmus MC

Rotterdam, Netherlands

Location

UMC Utrecht

Utrecht, Netherlands

Location

Related Publications (1)

• Guchelaar NAD, Mathijssen RHJ, de Boer M, van Bekkum ML, Heijns JB, Vriens BEPJ, van Rosmalen MM, Kessels LW, Hamming L, Beelen KJ, Nieboer P, van den Berg SM, Hoop EO, Bijlsma RM, Bos MEMM; Dutch Breast Cancer Research Group (BOOG). Trifluridine-tipiracil in previously treated patients with oestrogen receptor-positive, HER2-negative metastatic breast cancer (BOOG 2019-01 TIBET trial): a single-arm, multicentre, phase 2 trial. EClinicalMedicine. 2025 Jan 27;80:103065. doi: 10.1016/j.eclinm.2024.103065. eCollection 2025 Feb.

  PMID: 40017682 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

trifluridine tipiracil drug combination

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• A. Elise van Leeuwen-Stok, PhD

  BOOG Study Center

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: Multicenter, single arm, phase 2 study evaluating the efficacy and safety of trifluridine/tipiracil in women with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy. Study medication should be started within 3 days after completion of screening and continue until a study treatment discontinuation criterion is met. Trifluridine/tipiracil will be administered orally BID on days 1 through 5, with the first dose administered in the morning of day 1 of each cycle and the last dose administered in the evening of day 5, followed by a recovery period from day 6 through day 7. Trifluridine/tipiracil will be administered orally BID on days 8 through 12, with the first dose administered in the morning of day 8 of each cycle and the last dose administered in the evening of day 12, followed by a recovery period from day 13 through day 28. Each cycle will be 28 days.

Study Record Dates

• First Submitted: July 22, 2020
• First Posted: July 28, 2020
• Study Start: September 25, 2020
• Primary Completion: January 8, 2024
• Study Completion: November 1, 2025
• Last Updated: September 19, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (10)