TAS102 in patients with ER-positive, HER2-negative advanced breast cancer (TIBET study)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

BOOG Study Center B.V.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

25 Sep 2020 → 16 Feb 2026

Decision date (initial)

2024-11-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-519204-27-00

EudraCT number

2019-001706-15

ClinicalTrials.gov

NCT04489173

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To evaluate the efficacy of trifluridine/tipiracil by determination of the percentage of patients being progression free at 8 weeks on trifluridine/tipiracil prescribed for ER-positive, HER2-negative advanced breast cancer patients previously treated with 2 or 3 lines of chemotherapy including taxane and for metastatic breast cancer capecitabine

Secondary objectives 4

1. Progression free survival
2. Response rate CR/PR at 16 weeks
3. Adverse Events
4. Quality of Life

Conditions and MedDRA coding

Advanced breast cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 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
2. Documented ER positive (10%) and/or PR positive (10%) and HER2 negative metastatic breast cancer
3. Progressive disease based on imaging
4. 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.
5. Evaluable disease as defined per RECIST v.1.1. 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.
6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
7. Life expectancy of ≥ 12 weeks
8. 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
9. Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE version 4.0 Grade ≤1, except alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion.

Exclusion criteria 11

1. HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive) and ER-negative patients are not eligible
2. No more than two lines of chemotherapy for advanced disease
3. Remaining side-effects from previous chemotherapy > grade 1 (except for alopecia)
4. 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.
5. 30% 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.
6. 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.
7. 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)
8. Previously received trifluridine/tipiracil
9. 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 (see section 4.4 of the SmPC). (APPENDIX C)
10. 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.
11. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage of patients being progression free at 8 weeks on trifluridine/tipiracil prescribed for ER-positive, HER2-negative advanced breast cancer patients previously treated with a taxane and capecitabine

Secondary endpoints 4

1. Progression free survival
2. Response rate CR/PR at 16 weeks
3. Adverse Events
4. Quality of Life

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

BOOG Study Center B.V.

Sponsor organisation

BOOG Study Center B.V.

Address

Moreelsepark 1

City

Utrecht

Postcode

3511 EP

Country

Netherlands

Scientific contact point

Organisation

BOOG Study Center B.V.

Contact name

BOOG Study Center

Public contact point

Organisation

BOOG Study Center B.V.

Contact name

BOOG Study Center

Third parties 3

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications