Efficacy and Safety of Intrathecal Administration of Thiotepa in Combination With Trastuzumab in Breast Cancer With Leptomeningeal Metastasis

NCT ID: NCT07263425

Last Updated: 2025-12-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

26 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-10-27

Study Completion Date

2027-10-27

Brief Summary

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Evaluate the efficacy and safety of Intrathecal Administration of Thiotepa in Combination with Trastuzumab via the Ommaya Reservoir in Breast Cancer with Leptomeningeal Metastasis

Detailed Description

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This was a II, single-arm, prospective, multicenter study designed to estimate the efficacy and safety of intrathecal administration of thiotepa in combination with Trastuzumab via the Ommaya Reservoir in HER2-positive breast cancer with leptomeningeal metastasis.

The primary end point was iORR \[complete response (CR) + partial response (PR)\] according to RANO-LM. Scoring based on radiographic assessment in leptomeningeal metastases . A composite score (total score) is calculated and compared with the baseline total score. A 25% worsening in the current score relative to baseline defines radiographic progressive disease. A 50% improvement in the current score defines a radiographic partial response. Resolution of all baseline radiographic abnormalities defines a complete response. All other situations define stable disease. The secondary end points were changes in iPFS,PFS, OS, and exploratory analysis of the relationship between molecular markers and therapeutic efficacy.

This study is planned to include 26 patients with leptomeningeal metastasis from breast cancer who meet the entry criteria.

Conditions

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Leptomeningeal Metastasis of HER2-positive Breast Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Experimental

Intrathecal chemotherapy group Patients received intrathecal 150mg Trastuzumab combination with 10mg thiotepa once every three weeks until an event that meets the criteria for termination occurs.

Group Type EXPERIMENTAL

Intrathecal Administration of Thiotepa in Combination with Trastuzumab via the Ommaya Reservoir

Intervention Type DRUG

Intrathecal chemotherapy group Patients received intrathecal 150mg Trastuzumab combination with 10mg thiotepa once every three weeks until an event that meets the criteria for termination occurs.

Interventions

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Intrathecal Administration of Thiotepa in Combination with Trastuzumab via the Ommaya Reservoir

Intrathecal chemotherapy group Patients received intrathecal 150mg Trastuzumab combination with 10mg thiotepa once every three weeks until an event that meets the criteria for termination occurs.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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The Affiliated Brain Hospital of Nanjing Medical University

OTHER_GOV

Sponsor Role collaborator

The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Jiangsu Provincial People's Hospital

Nanjing, Jiangsu, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Wei Li, Ph.D

Role: CONTACT

025-68307102

Facility Contacts

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Wei Li, Ph.D

Role: primary

025-68307102

Role: backup

Other Identifiers

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Ommaya 02

Identifier Type: -

Identifier Source: org_study_id

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