Clinical trial NCT06462092: Sacituzumab Govitecan and Intrathecal Chemotherapy for Treating Leptomeningeal Metastases From Her2-negative Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Leptomeningeal Metastases
Keywords: Breast cancer
Her2- (Human Epidermal Growth Factor Receptor 2 Negative)
Leptomeningeal Metastases
Sacituzumab Govitecan
Pemetrexed
Intrathecal chemotherapy
Lead sponsor: Guangzhou Medical University
Sponsor class: OTHER
First posted: 2024-06-17
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility 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.

Primary outcomes:
measure: Maximal tolerated dose
timeFrame: From the beginning of the treatment until two months after the treatment.
Secondary outcomes:
measure: Incidence of treatment-related adverse events
timeFrame: From the beginning of the treatment until two months after the treatment.
measure: Clinical response rate
timeFrame: From the beginning of the treatment until two months after the treatment or when patient died.
Other outcomes:
Locations:
Study officials:
affiliation: Huizhou Hospital of Guangzhou Medical University
name: Zhenyu Pan
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
citation: 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.