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

NCT06462092 | Recruiting Phase 1 DMC

• 1 other identifier: 2024-KY-027-01
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Leptomeningeal Metastases

Keywords

Breast cancer; Her2- (Human Epidermal Growth Factor Receptor 2 Negative); Leptomeningeal Metastases; Sacituzumab Govitecan; Pemetrexed; Intrathecal chemotherapy

Outcome Measures

Primary Outcomes (1)

• Maximal tolerated dose

  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 Outcomes (2)

• Incidence of treatment-related adverse events

  From the beginning of the treatment until two months after the treatment.

• Clinical response rate

  From the beginning of the treatment until two months after the treatment or patient death.

Study Arms (1)

Group

EXPERIMENTAL

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; Drug: Pemetrexed

Interventions

Sacituzumab Govitecan DRUG

Patients receive Sacituzumab Govitecan 10mg/kg by intravenous infusion on days 1 and 8. Treatment cycles are every 21 days.

Also known as: Trodelvy

Group

Pemetrexed DRUG

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).

Also known as: ALIMTA

Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A clear histopathologic diagnosis of breast cancer with HER2-negative subtype (including IHC 0, IHC 1+ or IHC 2+ and ISH negative);
• 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;
• Age ≥ 18 years old.

You may not qualify if:

• 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;
• 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;
• Pregnant and breastfeeding female patients; women of childbearing age who are unwilling or unable to use effective contraception;
• Any other condition that, in the opinion of the investigator, makes the patient ineligible for participation in the study.

Sponsors & Collaborators

• Guangzhou Medical University: lead

Study Sites (1)

The Affiliated Huizhou Hospital, Guangzhou Medical University

Huizhou, Guangdong, 516000, China

RECRUITING

Related Publications (4)

• Pan Z, Yang G, Cui J, Li W, Li Y, Gao P, Jiang T, Sun Y, Dong L, Song Y, Zhao G. A Pilot Phase 1 Study of Intrathecal Pemetrexed for Refractory Leptomeningeal Metastases From Non-small-cell Lung Cancer. Front Oncol. 2019 Aug 30;9:838. doi: 10.3389/fonc.2019.00838. eCollection 2019.

  PMID: 31544065 BACKGROUND

• Pan Z, Yang G, He H, Cui J, Li W, Yuan T, Chen K, Jiang T, Gao P, Sun Y, Cong X, Li Z, Wang Y, Pang X, Song Y, Zhao G. Intrathecal pemetrexed combined with involved-field radiotherapy as a first-line intra-CSF therapy for leptomeningeal metastases from solid tumors: a phase I/II study. Ther Adv Med Oncol. 2020 Jul 17;12:1758835920937953. doi: 10.1177/1758835920937953. eCollection 2020.

  PMID: 32733606 BACKGROUND

• Rugo HS, Bardia A, Marme F, Cortes J, Schmid P, Loirat D, Tredan O, Ciruelos E, Dalenc F, Gomez Pardo P, Jhaveri KL, Delaney R, Valdez T, Wang H, Motwani M, Yoon OK, Verret W, Tolaney SM. Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2023 Oct 21;402(10411):1423-1433. doi: 10.1016/S0140-6736(23)01245-X. Epub 2023 Aug 23.

  PMID: 37633306 BACKGROUND

• Bardia A, Hurvitz SA, Tolaney SM, Loirat D, Punie K, Oliveira M, Brufsky A, Sardesai SD, Kalinsky K, Zelnak AB, Weaver R, Traina T, Dalenc F, Aftimos P, Lynce F, Diab S, Cortes J, O'Shaughnessy J, Dieras V, Ferrario C, Schmid P, Carey LA, Gianni L, Piccart MJ, Loibl S, Goldenberg DM, Hong Q, Olivo MS, Itri LM, Rugo HS; ASCENT Clinical Trial Investigators. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2021 Apr 22;384(16):1529-1541. doi: 10.1056/NEJMoa2028485.

  PMID: 33882206 BACKGROUND

MeSH Terms

Conditions

Meningeal Carcinomatosis; Breast Neoplasms

Interventions

sacituzumab govitecan; Pemetrexed

Condition Hierarchy (Ancestors)

Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Zhenyu Pan

  Huizhou Hospital of Guangzhou Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhenyu Pan

CONTACT

+8618718178286; dr-zypan@163.com

Guozi Yang

CONTACT

+8615804302755; guoziyang_1982@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 12, 2024
• First Posted: June 17, 2024
• Study Start: January 1, 2026
• Primary Completion (Estimated): January 15, 2027
• Study Completion (Estimated): June 15, 2027
• Last Updated: September 29, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP
• Time Frame: Starting 6 months after publication.
• Access Criteria: Individual participant data will be public accessable via contacting with principal investigator by email within 6 months after the trial complete.

Locations

CN (1)