Sacituzumab Govitecan and Intrathecal Chemotherapy for Treating Leptomeningeal Metastases From Her2-negative Breast Cancer

September 24, 2025 updated by: Zhenyu Pan, Guangzhou Medical University

A Phase I/II Clinical Study of Sacituzumab Govitecan Combined With Intrathecal Chemotherapy for the Treatment of Leptomeningeal Metastases From Her2-negative Breast Cancer

Leptomeningeal metastases (LM) is a lethal complication of malignant tumors, characterized by tumor cell invasion and proliferation within the subarachnoid space. LM from HER2-negative breast cancer remains challenging to treat, with a median overall survival of only 3-6 months despite aggressive therapy. This open-label, uncontrolled Phase I/II clinical study aims to evaluate the safety, feasibility, and potential efficacy of Sacituzumab Govitecan in combination with intrathecal pemetrexed chemotherapy for LM from HER2-negative breast cancer, with the objective of identifying a more effective treatment strategy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This study is a single-arm, prospective Phase I/II clinical trial, evaluating the safety, feasibility, and potential efficacy of combining Sacituzumab Govitecan with intrathecal pemetrexed chemotherapy for leptomeningeal metastases from HER2-negative breast cancer. The treatment regimen includes intravenous administration of Sacituzumab Govitecan (10 mg/kg) on Days 1 and 8 of each 21-day cycle, continuing until disease progression or unacceptable toxicity. Intrathecal pemetrexed chemotherapy is initiated on Day 2 via intracerebroventricular or lumbar puncture. The treatment is divided into three phases: induction therapy, 15 mg twice weekly for 2 weeks; consolidation therapy, once weekly for 4 weeks; maintenance therapy, once monthly for patients with an effective response until relapse or death. In the Phase I cohort, 3-6 patients were enrolled. If dose-limiting toxicity (DLT) occurred in ≥2 patients, the intrathecal dose of pemetrexed was reduced to 10 mg, and enrollment continued to ensure a total of 6 evaluable patients. If DLT recurred in ≥2 patients among the subsequently enrolled patients, the trial would be terminated. If DLT occurred in ≤1 patient, the trial would proceed to Phase II.

Study Type

Interventional

Enrollment (Estimated)

34

Phase

  • Phase 2
  • Phase 1

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 Contact Backup

Study Locations

  • China
    • Guangdong
      • Huizhou, Guangdong, China, 516000
        • Recruiting
        • The Affiliated Huizhou Hospital, Guangzhou Medical University
        • Contact:
        • Contact:
        • Principal Investigator:
          • Zhenyu Pan, PhD,MD

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:

  1. A clear histopathologic diagnosis of breast cancer with HER2-negative subtype (including IHC 0, IHC 1+ or IHC 2+ and ISH negative);
  2. Cerebrospinal fluid cytology confirms the presence of leptomeningeal metastases; or imaging findings combined with clinical symptoms and signs are consistent with the diagnosis of leptomeningeal metastases;
  3. Age ≥ 18 years old.

Exclusion Criteria:

  1. Inadequate organ function: 1) Blood tests: ANC ≤ 1.5 x 10^9/L, PLT ≤ 90 x 10^9/L, Hb ≤ 90 g/L; 2) Blood biochemistry tests: TBIL ≥ 1.5 times the upper limit of normal; 3) ALT and AST ≥ 2.5 times the upper limit of normal;
  2. Presence of serious and/or uncontrolled comorbidities that may affect participation: 1) Allergy to study drugs or adjuvant materials; 2) History of immunodeficiency (e.g., HIV-positive or other acquired or congenital immunodeficiency disease); 3) Severe concomitant diseases;
  3. Pregnant and breastfeeding female patients; women of childbearing age who are unwilling or unable to use effective contraception;
  4. Any other condition that, in the opinion of the investigator, makes the patient ineligible for participation in the study.

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: Group
In the Phase I cohort, a minimum of 3 patients and a maximum of 6 patients were enrolled. If DLT occurred in ≥2 patients, the dose of intrathecal pemetrexed was reduced to 10 mg, and enrollment continued with 6 consecutive patients. If DLT recurred in ≥2 patients, the trial was terminated. if DLT occurred in ≤1 patient, the study advanced to Phase II.
Drug: Sacituzumab Govitecan
Patients receive Sacituzumab Govitecan 10mg/kg by intravenous infusion on days 1 and 8. Treatment cycles are every 21 days.
Other Names:
  • Trodelvy
Drug: Pemetrexed
Intrathecal pemetrexed chemotherapy, administered via intracerebroventricular or lumbar puncture, consists of three phases: induction therapy (15 mg twice weekly for 2 weeks), consolidation therapy (once weekly for 4 consecutive weeks), and maintenance therapy (once monthly).
Other Names:
  • ALIMTA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximal tolerated dose
Time Frame: From the beginning of the treatment until two months after the treatment.
DLT was defined as Grade 3 neurological toxicities (e.g., chemical meningitis) or any Grade 4 toxicity. If DLT occurred in more than two patients at a given dose level, that dose level was deemed intolerable, and the maximal tolerated dose (MTD) was exceeded. In such cases, an additional three patients were treated at the next lower dose level. The MTD was defined as the dose level at which 0/3 or 1/6 patients experienced DLT, given that at least two patients experiencing DLT at the higher dose.
From the beginning of the treatment until two months after the treatment.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of treatment-related adverse events
Time Frame: From the beginning of the treatment until two months after the treatment.
The incidence of treatment-related adverse events (AEs) was assessed to determine tolerability and safety. AEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE, version 4.03), with Grades 3-5 defined as moderate to severe events.
From the beginning of the treatment until two months after the treatment.
Clinical response rate
Time Frame: From the beginning of the treatment until two months after the treatment or patient death.
The Response Assessment in Neuro-Oncology (RANO) criteria for leptomeningeal metastases were used to assess clinical response in this study.
From the beginning of the treatment until two months after the treatment or patient death.

Collaborators and Investigators

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

Sponsor

Guangzhou Medical University

Investigators

  • Principal Investigator: Zhenyu Pan, Huizhou Hospital of Guangzhou Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Estimated)

January 1, 2026

Primary Completion (Estimated)

January 15, 2027

Study Completion (Estimated)

June 15, 2027

Study Registration Dates

First Submitted

June 12, 2024

First Submitted That Met QC Criteria

June 12, 2024

First Posted (Actual)

June 17, 2024

Study Record Updates

Last Update Posted (Estimated)

September 29, 2025

Last Update Submitted That Met QC Criteria

September 24, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-KY-027-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All individual participant data that underlie results in a publication will be available to other researchers.

IPD Sharing Time Frame

Starting 6 months after publication.

IPD Sharing Access Criteria

Individual participant data will be public accessable via contacting with principal investigator by email within 6 months after the trial complete.

IPD Sharing Supporting Information Type

  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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