Intrathecal thiotepa plus trastuzumab for HER2‑positive breast cancer with leptomeningeal metastasis
Efficacy and Safety of Intrathecal Administration of Thiotepa in Combination With Trastuzumab Via the Ommaya Reservoir in Breast Cancer With Leptomeningeal Metastasis: a Phase II Multicenter Clinical Trial
Testing whether injecting thiotepa together with trastuzumab into the cerebrospinal fluid through an Ommaya reservoir helps people with HER2‑positive breast cancer that has spread to the leptomeninges.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 26 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | Female |
| Sponsor | The First Affiliated Hospital with Nanjing Medical University Academic / other |
| Drugs / interventions | Trastuzumab |
| Locations | 1 site (Nanjing, Jiangsu) |
| Trial ID | NCT07263425 on ClinicalTrials.gov |
What this trial studies
This is a single‑arm, prospective Phase 2 multicenter trial enrolling about 26 patients with HER2‑positive breast cancer and leptomeningeal metastasis to receive intrathecal thiotepa combined with trastuzumab via an Ommaya reservoir. The primary endpoint is intracranial objective radiographic response rate (iORR) using the RANO‑LM radiographic scoring system, with radiographic progression and response defined by percentage change from baseline. Secondary endpoints include intracranial progression‑free survival, overall progression‑free survival, overall survival, and exploratory correlations between molecular markers and response. Patients must have confirmed HER2 positivity, leptomeningeal disease, and either an implanted or implantable Ommaya reservoir and meet hematologic and organ function requirements.
Who should consider this trial
Good fit: Adults with histologically or cytologically confirmed HER2‑positive breast cancer and leptomeningeal metastasis who have or can receive an Ommaya reservoir and meet performance status and laboratory safety criteria are the intended participants.
Not a fit: Patients without HER2 overexpression/amplification, those unable to undergo Ommaya placement, or those with very poor organ function or performance status are unlikely to benefit from this intrathecal regimen.
Why it matters
Potential benefit: If successful, this approach could improve radiographic responses and potentially prolong survival by delivering targeted and cytotoxic agents directly into the CSF for patients with leptomeningeal HER2‑positive breast cancer.
How similar studies have performed: Small case series and early reports have shown signals of activity for intrathecal trastuzumab and for intrathecal thiotepa individually, but larger controlled data on the combination are limited and the approach remains relatively untested in randomized trials.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:The subjects must meet all of the following criteria simultaneously: * Histologically or cytologically confirmed HER-2 positive breast cancer (immunohistochemistry indicates HER-2 3+ and/or fluorescence in situ hybridization indicates HER-2 gene amplification) * Diagnosed with breast cancer with leptomeningeal metastasis based on cerebrospinal fluid cytology combined with central nervous system function and brain imaging findings * The patient has an Ommaya reservoir implanted or is eligible for implantation * KPS ≥ 30 * Adequate bone marrow and liver and kidney function reserves: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, hemoglobin ≥ 90 g/L. International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN. Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN. Total serum bilirubin ≤ 1.5 x ULN (patients with Gilbert's syndrome can be enrolled if total bilirubin \< 3 x ULN). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN; if the patient has liver metastasis, this criterion is AST and ALT ≤ 5 x ULN. * Female, aged between 18 and 75 years old * Left ventricular ejection fraction (LVEF) \> 50% * Voluntary signing of informed consent form Exclusion Criteria: Patients meeting any of the following criteria are not eligible to be included in this study: * Subjects with other malignant tumors, excluding skin basal cell carcinoma and carcinoma in situ * Presence of severe or uncontrollable systemic diseases, including uncontrollable hypertension or active bleeding tendency * Patients judged by the investigator to be unsuitable for participation in the trial, or those with factors that may affect the patient's compliance with the protocol * Toxicity caused by previous treatment has not recovered to normal state or is grade 1 according to NCI-CTCAE 5.0 * Allergic to or with metabolic disorders to the drugs in this protocol * Pregnant or lactating women, or women with pregnancy plans during the study period and within 6 months after the last administration * Patients participating in other clinical studies simultaneously
Where this trial is running
Nanjing, Jiangsu
- Jiangsu Provincial People's Hospital — Nanjing, Jiangsu, China (Recruiting)
Study contacts
- Study coordinator: Wei Li, Ph.D
- Email: real.lw@163.com
- Phone: 025-68307102
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.