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

Leptomeningeal Metastases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06462092
• Other study ID #: 2024-KY-027-01
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: June 15, 2024
• Est. completion date: June 15, 2027

Study information

• Verified date: June 2024
• Source: Guangzhou Medical University
• Contact: Zhenyu Pan
• Phone: +8618718178286
• Email: dr-zypan[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 34
• Est. completion date: June 15, 2027
• Est. primary completion date: January 15, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Leptomeningeal Metastases
• Meningeal Carcinomatosis
• Neoplasm Metastasis

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Guangzhou Medical University

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximal tolerated dose	A dose-limiting toxicity (DLT) was defined as grade 3 neurological toxicities (e.g. chemical meningitis) or other grade 4 toxicity. If more than two patients experienced a DLT, that level was considered too toxic. The maximal tolerated dose (MTD) was exceeded and an additional three patients should be treated at the next lower dose level. The MTD was defined as the dose where 0/3 or 1/6 patients experienced a DLT with at least two patients encountering DLT at the higher dose.	From the beginning of the treatment until two months after the treatment.
Secondary	Incidence of treatment-related adverse events	The incidence of treatment-related adverse events were measured for determining tolerability and safety. Adverse events (AEs) are evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE, version 4.03). Events of grade 3-5 are defined as moderate and severe adverse events.	From the beginning of the treatment until two months after the treatment.
Secondary	Clinical response rate	The Response Assessment in Neuro-Oncology (RANO) criteria proposal for response criteria of leptomeningeal metastases was used to assess the clinical response in this study.	From the beginning of the treatment until two months after the treatment or when patient died.