Efficacy and Safety of Intrathecal Administration of Thiotepa in Combination With Methotrexate in Breast Cancer With Leptomeningeal Metastasis

NCT06543992 | Recruiting Phase 2

• 1 other identifier: NJMU-BC04
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

Evaluate the efficacy and safety of Intrathecal Administration of Thiotepa in Combination with Methotrexate via the Ommaya Reservoir in Breast Cancer with Leptomeningeal Metastasis

Conditions

Leptomeningeal Metastasis of Breast Cancer

Keywords

methotrexate; thiotepa; intrathecal chemotherapy

Outcome Measures

Primary Outcomes (1)

• Intracranial Overall Response Rate

  Intracranial overall response rate (iORR) is defined as the proportion of patients whose best overall response is either complete response (CR) or partial response (PR), as per local review and according to RANO-LM.

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Secondary Outcomes (7)

• Intracranial Progression Free Survival

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Intracranial Duration of Response

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Overall Response Rate

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Progression Free Survival

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Overall Survival

  From date of randomization until the date of death from any cause, assessed up to 100 months

Study Arms (1)

Intrathecal chemotherapy group

EXPERIMENTAL

Intraventricular administration was carried out using an Ommaya reservoir. The treatment protocol consisted of an induction phase: thiotepa (10 mg) and MTX (15 mg) were administered twice weekly for a total of four consecutive doses, followed by a maintenance phase in which the same agents and dosages were administered every three weeks. Treatment was continued until the occurrence of an event meeting predefined discontinuation criteria.

Drug: Intrathecal Administration of Thiotepa in Combination with Methotrexate via the Ommaya Reservoir

Interventions

Intrathecal Administration of Thiotepa in Combination with Methotrexate via the Ommaya Reservoir DRUG

Patients received 15 mg MTX intrathecally combined with 10 mg thiotepa twice a week for 2 weeks (4 injections), followed by a maintenance phase in which the same agents and dosages were administered every three weeks until an event meeting the termination criteria occurs.

Intrathecal chemotherapy group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is an adult female ≥18 and ≤75 years old at the time of informed consent.
• ECGO rating 0-3.
• Histologically or cytologically confirmed breast cancer.
• A new diagnosis of LM, established either by the presence of malignant cells in the CSF or by the combination of characteristic clinical manifestations and magnetic resonance imaging (MRI) findings
• Patients can be implanted or have been implanted with Ommaya reservoirs;
• Patient must have at least one measurable lesion (according to RECIST 1.1 criteria);
• Postmenopausal or pre/perimenopausal female patients are eligible for enrolment; pre or perimenopausal female patients must be willing to receive LHRHa during the study period.
• All patients were required to meet the following laboratory biochemical values prior to enrolment:
• Haematology: Hb ≥90 g/L, WBC ≥3.5×109/L, ANC ≥1.5×109/L, PLT ≥100×109/L;
• Liver function: for those without liver metastases, AST, ALT, ALP ≤2.5 times the upper limit of normal values, and ≤1.25 x the upper limit of normal values for total bilirubin; for those with liver metastases, AST, ALT, ALP ≤ 5 times the upper limit of normal value, and total bilirubin ≤ 1.5 x upper limit of normal value.

You may not qualify if:

• Patients with other malignant tumors, excluding basal cell carcinoma and carcinoma in situ
• Patients with severe or uncontrolled systemic disease, including uncontrolled hypertension or active bleeding tendency
• The investigator considers the patient unsuitable for entry into this study.
• Patients with toxicity from prior therapy that has not returned to normal or NCI-CTCAE grade 5.0
• Patients who have a drug allergy or metabolic disorder to the drugs in this regimen
• Pregnant or lactating women (women of childbearing age must have had a negative pregnancy test within 14 days prior to the first dose; if positive, pregnancy must be ruled out by ultrasound).
• Patients who are concurrently enrolled in other clinical studies

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead
• The Affiliated Brain Hospital of Nanjing Medical University: collaborator

Study Sites (1)

Jiangsu Provincial People's Hospital

Nanjing, Jiangsu, 210000, China

RECRUITING

Central Study Contacts

Wei Li, Ph.D

CONTACT

025-68307102; real.lw@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2024
• First Posted: August 9, 2024
• Study Start: August 8, 2024
• Primary Completion (Estimated): December 13, 2026
• Study Completion (Estimated): December 13, 2026
• Last Updated: July 21, 2026

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE

Locations

CN (1)