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Treatment for breast cancer patients with leptomeningeal disease

Multicentric Single Arm Phase II Study Evaluating the Efficacy of Association of Tucatinib, Capecitabine and Intra-CSF Trastuzumab in HER2 Amplified Breast Cancer Patients With Leptomeningeal Metastases

Phase 2 Interventional Unicancer · NCT05800275

This study is testing a new treatment combining tucatinib, capecitabine, and intrathecal trastuzumab to see if it can help people with HER2-positive metastatic breast cancer and leptomeningeal disease live longer.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment30 (estimated)
Ages18 Years and up
SexAll
SponsorUnicancer Academic / other
Drugs / interventionstrastuzumab, Tucatinib, radiation
Locations11 sites (Bordeaux and 10 other locations)
Trial IDNCT05800275 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of tucatinib and capecitabine combined with intrathecal trastuzumab in improving overall survival rates at 12 months for HER2-positive metastatic breast cancer patients who have developed leptomeningeal disease. Participants will receive oral and injectable medications specifically targeting their cancer. The study aims to provide a new therapeutic approach for patients requiring intrathecal therapy due to leptomeningeal progression.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed HER2-positive metastatic breast cancer and proven leptomeningeal progression.

Not a fit: Patients without HER2-positive breast cancer or those who do not have leptomeningeal disease may not benefit from this treatment.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival rates for patients with HER2-positive metastatic breast cancer and leptomeningeal disease.

How similar studies have performed: While there have been studies exploring treatments for leptomeningeal disease, this specific combination of therapies is novel and has not been extensively tested.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Patient must have signed a written informed consent form prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent;
2. Patients ≥18 years old;
3. Histologically confirmed metastatic breast cancer;
4. Histologically confirmed HER2 positive breast cancer, with HER2 positive defined by in situ hybridization (ISH), immunohistochemistry (IHC), or fluorescence in situ hybridization (FISH) methodology; Note: HER2 testing should be performed preferably metastatic site; any estrogen and progesterone (ER/PR) status is allowed;
5. Proven leptomeningeal progression defined by linear leptomeningeal metastases on magnetic resonance imaging (MRI) or the presence of breast cancer cells in CSF (obtained within 28 days before inclusion );
6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2;
7. Life expectancy ≥2 months;
8. Stable dose of steroids for at least 5 days prior to registration;
9. If symptomatic brain or leptomeningeal metastasis, local treatment (surgery, radiation therapy) is allowed until 2 weeks before inclusion but should have been completed no more than 8 weeks before inclusion and with no clinical indication for immediate re-treatment with local therapy in the opinion of the investigator;
10. Adequate hematological function within 14 days before inclusion: Absolute neutrophil count (ANC) ≥1.5 x 10⁹/L; platelets count ≥100 x 10⁹/L; and hemoglobin ≥9.0 g/dL;
11. Adequate liver function within 14 days before inclusion: total bilirubin ≤1.5 ULN (unless documented Gilbert's syndrome); AST and ALT ≤2.5 ULN (≤5 ULN in the presence of liver metastases);
12. Normal renal function within 14 days before inclusion: estimated creatinine clearance ≥60 mL/min according to the Cockcroft-Gault formula;
13. Adequate cardiac function:

    * 12 Lead electrocardiograms (ECG) with normal tracing or non-clinically significant changes that do not require medical intervention
    * QT/QTc interval ≤470 msec for woman and ≤450 msec for men (mean of replicate values, correction per institutional standard) on the ECG at the screening visit and a normal kaliemia
    * Left ventricular ejection fraction (LVEF) ≥55%
    * No history of Torsades de Pointes or other symptomatic QTc abnormality
14. Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to National cancer institute-Common terminology criteria for adverse events (NCI-CTCAE) version 5.0 grade 1 or 0 to baseline (except alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion);
15. Women of childbearing potential must have a negative pregnancy test (blood or urine test) within 14 days prior to inclusion;
16. Woman of childbearing potential and male patients must agree to use adequate contraception for the duration of trial participation and up to 7 months after completing treatment/therapy. Hormonal contraceptives such as birth control pills, patches, implants, or injections are not allowed in patients who are hormone receptor positive;
17. Patients affiliated to the social security system (or equivalent);
18. Patient must be willing and able to comply with the protocol for the duration of the trial including scheduled visits, treatment plan, laboratory tests, and examinations including follow-up.

Exclusion Criteria:

1. Used of a strong cytochrome P450 (CYP)2C8 inhibitor within 5 half-lives of the inhibitor, or use of a strong CYP3A4 or CYP2C8 inducer within 5 days prior to first dose of study treatment. Use of sensitive CYP3A substrates should be avoided one week before enrollment and during study treatment;
2. Previous treatment with Tucatinib or Capecitabine;
3. Severe leukopenia, neutropenia, or thrombocytopena, severe hepatic impairment, severe renal impairment (creatinine clearance below 30mL/min)
4. Recent or concomitant treatment with brivudine ;
5. Any antiplatelet or curative anticoagulant treatment for blood coagulation disorders;
6. Severe pre-existing cerebrovascular dysfunction or pathology such as stroke and intra-cerebral hematoma or uncontrolled intracerebral hypertension induced by brain metastasis;
7. Ventriculoperitoneal or atrial shunt, except if the valve is equipped with an on-off device and that the patient's condition allows for to remain in the off position for 6 hours after each injection of trastuzumab;
8. Known history of testing positive for HIV or known acquired immunodeficiency syndrome;
9. Carriers of Hepatitis B or Hepatitis C or have other known chronic liver disease;
10. Uncontrolled hypertension;
11. Uncontrolled infection;
12. Severe dyspnea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy;
13. Pregnant or breast-feeding women;
14. Known prior severe hypersensitivity to tucatinib or compounds chemically or/and biologically similar or any component in its formulation;
15. Hypersensitivity to trastuzumab, murine proteins, or to any of the excipients in its formulation;
16. Known prior severe hypersensitivity to capecitabine or to any of the excipients or fluorouracil;
17. Known complete dihydropyrimidine dehydrogenase (DPD) deficiency (if applicable);
18. Inability to swallow tablets or significant gastrointestinal disease which would preclude the adequate oral absorption of medications;
19. Prior history of other malignancies other than study disease (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the patient has been free of the disease for at least 5 years;
20. Person deprived of their liberty or under protective custody or guardianship;
21. Participation in another therapeutic trial within the 30 days prior to treatment initiation;
22. Patients with any other disease or illness, which requires hospitalization or is incompatible with the trial treatment, are not eligible. Patients unwilling or unable to comply with trial obligations for geographic, social, or physical reasons, or who are unable to understand the purpose and procedures of the trial.

Where this trial is running

Bordeaux and 10 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Leptomeningeal MetastasisLeptomeningeal DiseaseHER2-positive Metastatic Breast CancerIntrathecal injectionBreast Cancer MetastaticIntrathecal trastuzumabCapecitabineTucatinib
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.