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

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

Study Purpose

Leptomeningeal metastases is a specific pattern of central involvement in which tumor cells invade and proliferate in the subarachnoid space, and is a lethal complication of malignant tumors. Leptomeningeal metastases from Her2-negative breast cancer is still tricky to treat at present, with an overall median survival of only 3-6 months, even after aggressive treatment. This study is an open, uncontrolled phase I/II clinical study 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 in search of a more effective treatment.

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 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.

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	Not yet recruiting
Countries
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 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 & Interventions

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.