Clinical Trial Finder

Inclusion Criteria:

1. A clear histopathologic diagnosis of breast cancer with subtype Her2- (including IHC 0, IHC 1+ or IHC 2+ and ISH negative). 2. Cerebrospinal fluid cytology diagnosis confirms the presence of leptomeningeal metastases; or imaging combined with patient 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, including HIV-positive or other acquired or congenital immunodeficiency diseases; 3) severe concomitant diseases; 3. Pregnant and breastfeeding female patients; women of childbearing age who are unwilling to Female patients of childbearing age who are using effective contraception; 4. Any other condition that, in the opinion of the investigator, makes the patient ineligible for participation in the study.

This study is a single-arm prospective phase I/II clinical trial to observe the safety, feasibility, and potential efficacy of Sacituzumab Govitecan combined with pemetrexed intrathecal chemotherapy in the treatment of patients with Her2-negative breast cancer leptomeningeal metastases. Patients were treated with Sacituzumab Govitecan 10mg/kg, infused intravenously on days 1 and 8. Treatment cycles were every 21 days and continued until disease progression or unacceptable toxicity. Pemetrexed intrathecal chemotherapy was initiated on Day 2 after Sacituzumab Govitecan administration. Pemetrexed intrathecal chemotherapy is administered by intracerebroventricular or lumbar puncture. Pemetrexed intrathecal chemotherapy is divided into induction, consolidation and maintenance phases. Induction therapy was first performed with a single dose of 15 mg twice a week for 2 weeks for a total of 4 doses. This was followed by consolidation therapy, 1 time per week for 4 consecutive weeks for a total of 4 times. Patients whose treatment was evaluated as effective were given maintenance therapy once a month until relapse or death. A minimum of 3 patients and a maximum of 6 patients were recruited into the phase I cohort. When dose-limiting toxicity occurred in ≥2 patients, the treatment regimen was considered to be excessively side-effective, and a reduction in the intrathecal chemotherapy dose of pemetrexed to a single 10-mg dose was given, with continued enrollment of 6 consecutive patients. If DLT occurred again in ≥2 patients, the trial would be stopped. Otherwise, the study entered a phase II trial when DLT occurred in ≤1 patient.

Arms

Experimental: Group

A minimum of 3 patients and a maximum of 6 patients were recruited per cohort in phase 1 study.. When dose-limiting toxicity occurred in ≥2 patients, the treatment regimen was considered to have too many side effects, and a reduction in the intrathecal chemotherapy dose of pemetrexed to a single dose of 10 mg was given, with continued enrollment of 6 consecutive patients. If DLT occurred again in ≥2 patients, the trial would be stopped. Otherwise, the study entered a phase 2 trial when DLT occurred in ≤1 patient.

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

Pemetrexed intrathecal chemotherapy is administered by intracerebroventricular or lumbar puncture. Pemetrexed intrathecal chemotherapy is divided into induction, consolidation and maintenance phases. Induction therapy was first performed with a single dose of 15 mg twice a week for 2 weeks for a total of 4 doses. This was followed by consolidation therapy, 1 time per week for 4 consecutive weeks for a total of 4 times.