Capecitabine, Tucatinib, and Intrathecal Trastuzumab for Breast Cancer Patients With Leptomeningeal Disease

NCT05800275 | Recruiting Phase 2 DMC

• 3 other identifiers: UC-BCG-22052022-001529-612022-502351-60-00
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 11

Brief Summary

The goal of this clinical trial is to evaluate the efficacy of tucatinib and capecitabine in combination with intrathecal trastuzumab on overall survival rate at 12 months in HER2-positive metastatic breast cancer (MBC) patients with proven leptomeningeal evolution and requiring intrathecal therapy.

Conditions

Leptomeningeal Metastasis; Leptomeningeal Disease; HER2-positive Metastatic Breast Cancer

Keywords

Intrathecal injection; Leptomeningeal Disease; Breast Cancer Metastatic; Leptomeningeal Metastasis; Intrathecal trastuzumab; Capecitabine; Tucatinib; HER2-positive Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• overall survival rate at 12 months

  12-month overall survival will be defined as the proportion of patients alive 12 months after treatment initiation.

  12 months

Secondary Outcomes (9)

• Clinical neurological symptoms relief

  At baseline, every week during treatment up to 18 months then every 9 weeks up to 42 months

• Progression free survival (PFS)

  From inclusion to disease progression or death, up to 42 months

• Overall survival (OS)

  From inclusion to death from any cause; up to 42 months

• Quality of life questionnaire - Core 30 (QLQ-C30)

  At baseline, every 3 weeks during treatment up to 18 months then every 9 weeks up to 42 months

• Quality of Life Questionnaire - Brain Cancer Module (QLQ-BN20)

  At baseline, every 3 weeks during treatment up to 18 months then every 9 weeks up to 42 months

Study Arms (1)

Tucatinib + Intrathecal Trastuzumab + Capecitabine

EXPERIMENTAL

Intra-CSF trastuzumab: 150 mg weekly Tucatinib: 300 mg orally twice daily Capecitabine: 1000 mg/m² orally twice daily on days 1-14 of each 21-day cycle

Drug: Tucatinib Oral Tablet; Drug: Capecitabine tablets; Drug: Trastuzumab Injection

Interventions

Tucatinib Oral Tablet DRUG

300 mg, twice daily

Tucatinib + Intrathecal Trastuzumab + Capecitabine

Capecitabine tablets DRUG

1000 mg/m², twice daily on days 1-14 of each 21-day cycle

Tucatinib + Intrathecal Trastuzumab + Capecitabine

Trastuzumab Injection DRUG

Intrathecal by lumbar puncture or Ommaya Reservoir, 150 mg weekly

Tucatinib + Intrathecal Trastuzumab + Capecitabine

Eligibility Criteria

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

You may qualify if:

• 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;
• Patients ≥18 years old;
• Histologically confirmed metastatic breast cancer;
• 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;
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2;
• Life expectancy ≥2 months;
• Stable dose of steroids for at least 5 days prior to registration;
• Adequate cardiac function:
• 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
• 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);
• 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;
• Patients affiliated to the social security system (or equivalent);

You may not qualify if:

• 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;
• Previous treatment with Tucatinib or Capecitabine;
• Severe leukopenia, neutropenia, or thrombocytopena, severe hepatic impairment, severe renal impairment (creatinine clearance below 30mL/min)
• Recent or concomitant treatment with brivudine ;
• Any antiplatelet or curative anticoagulant treatment for blood coagulation disorders;
• Severe pre-existing cerebrovascular dysfunction or pathology such as stroke and intra-cerebral hematoma or uncontrolled intracerebral hypertension induced by brain metastasis;
• 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;
• Known history of testing positive for HIV or known acquired immunodeficiency syndrome;
• Carriers of Hepatitis B or Hepatitis C or have other known chronic liver disease;
• Uncontrolled hypertension;
• Uncontrolled infection;
• Severe dyspnea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy;
• Pregnant or breast-feeding women;
• Known prior severe hypersensitivity to tucatinib or compounds chemically or/and biologically similar or any component in its formulation;
• Hypersensitivity to trastuzumab, murine proteins, or to any of the excipients in its formulation;

Sponsors & Collaborators

• UNICANCER: lead
• Seagen Inc.: collaborator

Study Sites (11)

Institut Bergonié

Bordeaux, 33000, France

WITHDRAWN

Centre François Baclesse

Caen, 14000, France

RECRUITING

Centre Jean Perrin

Clermont-Ferrand, 63011, France

RECRUITING

Centre Georges-François Leclerc

Dijon, 21000, France

RECRUITING

Centre Léon Bérard

Lyon, 69008, France

RECRUITING

Institut régional du Cancer de Montpellier

Montpellier, 34298, France

RECRUITING

Centre Antoine Lacassagne

Nice, 06189, France

RECRUITING

Institut Jean Godinot

Reims, 51100, France

RECRUITING

Centre Henri Becquerel

Rouen, 7600, France

RECRUITING

Institut de cancérologie Strasbourg Europe - ICANS

Strasbourg, 67200, France

RECRUITING

Gustave Roussy

Villejuif, 94805, France

RECRUITING

MeSH Terms

Conditions

Meningeal Carcinomatosis; Meningeal Neoplasms

Interventions

tucatinib; Capecitabine; Trastuzumab

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Louis LARROUQUERE

  Centre Léon Bérard, Lyon

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Telma ROQUE, PhD

CONTACT

+33 (0) 1 80 50 12 92; t-roque@unicancer.fr

Jérôme LEMONNIER, PhD

CONTACT

+33 (0) 1 71 93 67 02; j-lemonnier@unicancer.fr

Study Design

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

Study Record Dates

• First Submitted: March 23, 2023
• First Posted: April 5, 2023
• Study Start: December 18, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: November 18, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (11)