Actively Recruiting
Multicentric Single Arm Phase II Study Evaluating Tucatinib, Capecitabine, and Intrathecal Trastuzumab in HER2-Positive Breast Cancer Patients With Leptomeningeal Metastases
Led by UNICANCER · Updated on 2025-11-18
30
Participants Needed
11
Research Sites
26 weeks
Total Duration
On this page
Sponsors
U
UNICANCER
Lead Sponsor
S
Seagen Inc.
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating a combination of tucatinib, capecitabine, and intrathecal trastuzumab in patients with HER2-positive metastatic breast cancer that has spread to the leptomeninges, the membranes covering the brain and spinal cord. This Phase II study aims to assess the overall survival rate at 12 months in patients requiring intrathecal therapy due to leptomeningeal progression. The trial is sponsored by UNICANCER and focuses on patients with confirmed leptomeningeal metastases from breast cancer. Participants receive weekly intrathecal trastuzumab injections at a dose of 150 mg, oral tucatinib tablets of 300 mg twice daily, and capecitabine tablets of 1000 mg/m² twice daily on days 1 to 14 of each 21-day cycle. This single-arm study follows patients during treatment to monitor their response and safety over time. During the study, participants will undergo regular evaluations including neurological symptom assessments, imaging to track disease progression, quality of life questionnaires, cognitive testing, and toxicity monitoring. These assessments occur frequently during the first 18 months and then less often up to 42 months. Researchers will measure outcomes such as overall survival, progression-free survival, response in cerebrospinal fluid, and duration of leptomeningeal metastases response. The study requires participants to adhere to scheduled visits, laboratory tests, and follow-up procedures throughout the trial period.
CONDITIONS
Brief Title
Capecitabine, Tucatinib, and Intrathecal Trastuzumab for Breast Cancer Patients With Leptomeningeal Disease
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Patient has signed informed consent or consent confirmed by a trusted person if unable
- Age 18 years or older
- Histologically confirmed metastatic breast cancer
- HER2-positive breast cancer confirmed by ISH, IHC, or FISH
- Proven leptomeningeal progression by MRI or cancer cells in cerebrospinal fluid within 28 days
- ECOG performance status between 0 and 2
- Life expectancy of at least 2 months
- Stable steroid dose for at least 5 days before registration
- Local treatment of brain or leptomeningeal metastasis allowed if completed 2 to 8 weeks before inclusion
- Adequate blood counts within 14 days before inclusion
- Adequate liver function within 14 days before inclusion
- Normal kidney function with creatinine clearance 60 mL/min or higher
- Adequate cardiac function including normal ECG and LVEF 55% or higher
- Resolved toxic effects from prior therapy to grade 1 or 0 except alopecia
- Negative pregnancy test for women of childbearing potential within 14 days
- Agreement to use contraception during and for 7 months after trial if applicable
- Affiliated to social security or equivalent
- Willing and able to comply with protocol and follow-up
You will not qualify if you...
- Use of strong CYP2C8 inhibitors or CYP3A4/CYP2C8 inducers close to treatment start
- Previous treatment with tucatinib or capecitabine
- Severe leukopenia, neutropenia, thrombocytopenia, hepatic or renal impairment
- Recent or concurrent brivudine treatment
- Use of antiplatelet or anticoagulant treatment for blood disorders
- Severe cerebrovascular disease or uncontrolled brain pressure
- Ventriculoperitoneal or atrial shunt unless equipped and manageable
- Known HIV positive or AIDS diagnosis
- Carriers of Hepatitis B or C or chronic liver disease
- Uncontrolled hypertension or infection
- Severe breathing difficulty requiring oxygen
- Pregnant or breastfeeding women
- Severe allergies to tucatinib, capecitabine, trastuzumab, or formulation components
- Known DPD deficiency
- Inability to swallow tablets or gastrointestinal disease affecting absorption
- Other malignancies unless disease-free for 5 years except some skin or cervical cancers
- Under guardianship or deprived of liberty
- Participation in other therapeutic trials within 30 days
- Any other illness requiring hospitalization or incompatible with trial treatment
- Unable or unwilling to comply with trial requirements due to geographic, social, or physical reasons
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 18 months
Participants receive tucatinib orally twice daily, capecitabine orally twice daily on days 1-14 of each 21-day cycle, and intrathecal trastuzumab weekly by lumbar puncture or Ommaya Reservoir.
Weekly visits during treatment up to 18 months
Duration - Up to 24 months after treatment (up to 42 months total)
Participants are monitored for disease progression, survival, quality of life, cognitive function, and toxicity after treatment ends.
Visits every 9 weeks up to 42 months from inclusion
Trial Site Locations
Total: 11 locations
1
Institut Bergonié
Bordeaux, France, 33000
Withdrawn
2
Centre François Baclesse
Caen, France, 14000
Actively Recruiting
3
Centre Jean Perrin
Clermont-Ferrand, France, 63011
Actively Recruiting
4
Centre Georges-François Leclerc
Dijon, France, 21000
Actively Recruiting
5
Centre Léon Bérard
Lyon, France, 69008
Actively Recruiting
6
Institut régional du Cancer de Montpellier
Montpellier, France, 34298
Actively Recruiting
7
Centre Antoine Lacassagne
Nice, France, 06189
Actively Recruiting
8
Institut Jean Godinot
Reims, France, 51100
Actively Recruiting
9
Centre Henri Becquerel
Rouen, France, 7600
Actively Recruiting
10
Institut de cancérologie Strasbourg Europe - ICANS
Strasbourg, France, 67200
Actively Recruiting
11
Gustave Roussy
Villejuif, France, 94805
Actively Recruiting
Research Team
T
Telma ROQUE, PhD
J
Jérôme LEMONNIER, PhD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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