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

Official title

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

Overview

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

Detailed description

This was a II, single-arm, prospective, multicenter study designed to estimate the efficacy and safety of intrathecal administration of thiotepa in combination with methotrexate via the Ommaya Reservoir in breast cancer with leptomeningeal metastasis.

The primary end point was iORR \[complete response (CR) + partial response (PR)\] according to RANO-LM. Scoring based on radiographic assessment in leptomeningeal metastases . A composite score (total score) is calculated and compared with the baseline total score. A 25% worsening in the current score relative to baseline defines radiographic progressive disease. A 50% improvement in the current score defines a radiographic partial response. Resolution of all baseline radiographic abnormalities defines a complete response. All other situations define stable disease. The secondary end points were changes in iPFS, iDoR, ORR, PFS, OS, DoR and exploratory analysis of the relationship between molecular markers and therapeutic efficacy.

This study is planned to include 22 patients with leptomeningeal metastasis from breast cancer who meet the entry criteria.

Interventions

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

Primary outcome measures

• Intracranial Overall Response Rate [Time frame: 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 outcome measures (7)

• Intracranial Progression Free Survival [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: From date of randomization until the date of death from any cause, assessed up to 100 months]
• Duration of Response [Time frame: From date of randomization until the date of death from any cause, assessed up to 100 months]
• frequency/severity of adverse events, lab abnormalities [Time frame: 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]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Jiangsu Provincial People's Hospital — Nanjing

Identifiers

NCT: NCT06543992 · NJMU-BC04

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗