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

November 24, 2025 updated by: The First Affiliated Hospital with Nanjing Medical University

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

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

26

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210000
        • Recruiting
        • Jiangsu Provincial People's Hospital
        • Contact:
        • Principal Investigator:
          • Wei Li, Ph.D
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intracranial Overall Response Rate
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Intracranial overall response rate (iORR) is defined as the proportion of patients whose best overall response is either complete response (CR) or partial response (PR), as per local review and according to RANO-LM.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intracranial Progression Free Survival
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Intracranial progression-free survival (iPFS) is defined as the time from the date of randomization to the date of the first documented progression, as per local review and according to RANO-LM or death due to any cause.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Progression Free Survival
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Progression-free survival (PFS) is defined as the time from the date of randomization to the date of the first documented progression as per local review and according to RECIST 1.1 or death due to any cause.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Overall Survival
Time Frame: From date of randomization until the date of death from any cause, assessed up to 100 months
Overall survival is defined as the time from the date of randomization to the date of death due to any cause
From date of randomization until the date of death from any cause, assessed up to 100 months
frequency/severity of adverse events, lab abnormalities
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The First Affiliated Hospital with Nanjing Medical University

Collaborators

The Affiliated Brain Hospital of Nanjing Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 27, 2025

Primary Completion (Estimated)

October 27, 2027

Study Completion (Estimated)

October 27, 2027

Study Registration Dates

First Submitted

November 24, 2025

First Submitted That Met QC Criteria

November 24, 2025

First Posted (Estimated)

December 4, 2025

Study Record Updates

Last Update Posted (Estimated)

December 4, 2025

Last Update Submitted That Met QC Criteria

November 24, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • Ommaya 02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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