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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years - 75 Years
Gender	All

More Inclusion & Exclusion Criteria

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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06462092
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1/Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Guangzhou Medical University
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Zhenyu Pan
Principal Investigator Affiliation	Huizhou Hospital of Guangzhou Medical University
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	China
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Leptomeningeal Metastases

Additional Details

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.

Arms & Interventions

Arms

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.

Interventions

Drug: - Sacituzumab Govitecan

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

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).

Contact a Trial Team

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International Sites

Huizhou 1806776, Guangdong 1809935, China

Status

Recruiting

Address

The Affiliated Huizhou Hospital, Guangzhou Medical University

Huizhou 1806776, Guangdong 1809935, 516000

Site Contact

Zhenyu Pan, PhD,MD

[email protected]

+8618718178286

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