Using Thiotepa and Methotrexate for Breast Cancer with Leptomeningeal Metastasis

Efficacy and Safety of Intrathecal Administration of Thiotepa in Combination With Methotrexate Via the Ommaya Reservoir in Breast Cancer With Leptomeningeal Metastasis: a Phase II Multicenter Clinical Trial

This study is testing if a combination of thiotepa and methotrexate can help people with breast cancer that has spread to the protective layers around the brain feel better and live longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 22 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Female
• Sponsor: The First Affiliated Hospital with Nanjing Medical University (Academic / other)
• Drugs / interventions: Methotrexate
• Locations: 1 site (Nanjing, Jiangsu)
• Trial ID: NCT06543992 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of administering thiotepa in combination with methotrexate through an Ommaya Reservoir for patients with breast cancer that has spread to the leptomeninges. It is a Phase 2, single-arm, multicenter study involving 22 patients who meet specific eligibility criteria. The primary endpoint is the overall response rate based on radiographic assessments, while secondary endpoints include progression-free survival and overall survival. The study aims to provide insights into the effectiveness of this treatment combination in managing leptomeningeal metastasis.

Who should consider this trial

Good fit: Ideal candidates are adult females aged 18 to 75 with confirmed breast cancer and leptomeningeal metastasis who can tolerate the treatment.

Not a fit: Patients with significant comorbidities or those who do not meet the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for patients with leptomeningeal metastasis from breast cancer.

How similar studies have performed: While this approach is being tested in this specific context, similar intrathecal chemotherapy methods have shown promise in other studies.

Eligibility criteria

Inclusion Criteria:

1. Patient is an adult female ≥18 and ≤75 years old at the time of informed consent.
2. ECGO rating 0-3.
3. Histologically or cytologically confirmed breast cancer.
4. Cerebrospinal fluid cytology combined with central nervous system function and brain imaging demonstrated the diagnosis of breast cancer with meningeal metastases;
5. Patients can be implanted or have been implanted with Ommaya reservoirs;
6. Patient must have at least one measurable lesion (according to RECIST 1.1 criteria);
7. 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.
8. 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.

Exclusion Criteria:

1. Patients with other malignant tumors, excluding basal cell carcinoma and carcinoma in situ
2. Patients with severe or uncontrolled systemic disease, including uncontrolled hypertension or active bleeding tendency
3. The investigator considers the patient unsuitable for entry into this study.
4. Patients with toxicity from prior therapy that has not returned to normal or NCI-CTCAE grade 5.0
5. Patients who have a drug allergy or metabolic disorder to the drugs in this regimen
6. 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).
7. Patients who are concurrently enrolled in other clinical studies

Where this trial is running

Nanjing, Jiangsu

• Jiangsu Provincial People's Hospital — Nanjing, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Wei Li, Ph.D

Conditions Leptomeningeal Metastasis of Breast Cancer; methotrexate; thiotepa; intrathecal chemotherapy