Trial Title:
Capecitabine, Tucatinib, and Intrathecal Trastuzumab for Breast Cancer Patients with Leptomeningeal Disease
NCT ID:
NCT05800275
Condition:
Leptomeningeal Metastasis
Leptomeningeal Disease
HER2-positive Metastatic Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Neoplasm Metastasis
Meningeal Carcinomatosis
Meningeal Neoplasms
Capecitabine
Trastuzumab
Tucatinib
Conditions: Keywords:
Intrathecal injection
Leptomeningeal Disease
Breast Cancer Metastatic
Leptomeningeal Metastasis
Intrathecal trastuzumab
Capecitabine
Tucatinib
HER2-positive Metastatic Breast Cancer
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Tucatinib Oral Tablet
Description:
300 mg, twice daily
Arm group label:
Tucatinib + Intrathecal Trastuzumab + Capecitabine
Intervention type:
Drug
Intervention name:
Capecitabine tablets
Description:
1000 mg/m², twice daily on days 1-14 of each 21-day cycle
Arm group label:
Tucatinib + Intrathecal Trastuzumab + Capecitabine
Intervention type:
Drug
Intervention name:
Trastuzumab Injection
Description:
Intrathecal by lumbar puncture or Ommaya Reservoir, 150 mg weekly
Arm group label:
Tucatinib + Intrathecal Trastuzumab + Capecitabine
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.
Criteria for eligibility:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Institut Bergonié
Address:
City:
Bordeaux
Zip:
33000
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Laura SALABERT, MD
Facility:
Name:
Centre François Baclesse
Address:
City:
Caen
Zip:
14000
Country:
France
Status:
Recruiting
Contact:
Last name:
George EMILE, MD
Facility:
Name:
Centre Jean Perrin
Address:
City:
Clermont-Ferrand
Zip:
63011
Country:
France
Status:
Recruiting
Contact:
Last name:
Xavier DURANDO, Prof
Facility:
Name:
Centre Georges-François Leclerc
Address:
City:
Dijon
Zip:
21000
Country:
France
Status:
Recruiting
Contact:
Last name:
Isabelle DESMOULINS, MD
Facility:
Name:
Centre Léon Bérard
Address:
City:
Lyon
Zip:
69008
Country:
France
Status:
Recruiting
Contact:
Last name:
Louis LARROUQUERE, MD
Facility:
Name:
Institut régional du Cancer de Montpellier
Address:
City:
Montpellier
Zip:
34298
Country:
France
Status:
Recruiting
Contact:
Last name:
Amélie DARLIX, MD
Facility:
Name:
Centre Antoine Lacassagne
Address:
City:
Nice
Zip:
06189
Country:
France
Status:
Recruiting
Contact:
Last name:
Caroline BAILLEUX, MD
Facility:
Name:
Institut Jean Godinot
Address:
City:
Reims
Zip:
51100
Country:
France
Status:
Recruiting
Contact:
Last name:
Christelle JOUANNAUD, MD
Facility:
Name:
Centre Henri Becquerel
Address:
City:
Rouen
Zip:
7600
Country:
France
Status:
Recruiting
Contact:
Last name:
Jean-Christophe THERY, MD
Facility:
Name:
Institut de cancérologie Strasbourg Europe - ICANS
Address:
City:
Strasbourg
Zip:
67200
Country:
France
Status:
Recruiting
Contact:
Last name:
Philippe TRENZ, MD
Facility:
Name:
Gustave Roussy
Address:
City:
Villejuif
Zip:
94805
Country:
France
Status:
Recruiting
Contact:
Last name:
Caroline POISSON, MD
Start date:
December 18, 2023
Completion date:
June 2027
Lead sponsor:
Agency:
UNICANCER
Agency class:
Other
Collaborator:
Agency:
Seagen Inc.
Agency class:
Industry
Source:
UNICANCER
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05800275
