NCT07511725

Prophylactic Regimen With Intrathecal Thiotepa in SVZ-positive or Meningeal-risk Glioblastoma

A Pilot Study of Prophylactic Intrathecal Thiotepa Plus the Stupp Regimen for Glioblastoma With Subventricular Zone Contact or Intraoperative Ventricular Entry（PRISM-Trial）

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 38 (estimated)
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to test whether adding preventive intrathecal chemotherapy (thiotepa) to the standard Stupp regimen can lower the risk of leptomeningeal metastasis (LM) and extend survival in patients with newly diagnosed glioblastoma (GBM) whose tumors touch the sub-ventricular zone (SVZ+) or whose surgery accidentally opened the ventricle (VE). The main questions it aims to answer are: Can six weekly intrathecal injections of thiotepa (10 mg) given during chemoradiotherapy increase the chance of remaining free of LM at one year? Does the approach also prolong overall survival and progression-free survival compared with historical controls? Is the combination safe and well-tolerated in this high-risk population? Participants will: Receive maximal safe tumor resection followed by standard radiotherapy (60 Gy/30 fractions) plus daily temozolomide (75 mg/m²). Begin thiotepa injections (via lumbar puncture or Ommaya reservoir) within 1 week of starting radiotherapy, repeated every 7 days for 6 doses. Continue standard adjuvant temozolomide (150-200 mg/m² days 1-5/28) for 6 cycles. Understand that all procedures, toxicities and survival will be tracked for 2 years, with MRI and clinical visits every 4-8 weeks. Provide CSF and blood samples for exploratory biomarkers that may predict response or resistance.

Detailed description

This is a single-arm, prospective, phase II exploratory study designed to estimate the efficacy and safety of preventive intrathecal thiotepa combined with the Stupp protocol in adults with newly diagnosed, WHO grade 4 IDH-wildtype glioblastoma who are at very high risk of leptomeningeal seeding. Risk is defined as: 1. pre-operative MRI showing tumor in direct contact with the sub-ventricular zone (SVZ+), or 2. intra-operative cerebrospinal-fluid leak (ventricular entry, VE) documented in the surgical note and/or early post-operative imaging. SVZ+ and/or VE doubles the incidence of LM (≈25 % vs. 5-10 %) and shortens median overall survival to 12 months. Once LM occurs, median survival collapses to \< 4 months and no standard therapy exists. Thiotepa is a lipophilic alkylating agent that achieves high CSF concentrations, penetrates the pia-glial barrier, and has documented activity against meningeal glioma deposits with lower neuro-toxicity than methotrexate. Delivering thiotepa while the circulating tumor cell burden is still minimal ("adjuvant to adjuvant therapy") is therefore mechanistically attractive.

Conditions

• Glioblastoma (GBM)

Interventions

Type	Name	Description
PROCEDURE	Maximal surgical resection	Maximal-safe resection of the contrast-enhancing tumour; if VE occurs, rapid closure and post-op MRI within 72 h to document extent of resection and any blood/ tumour spillage into the ventricles.
RADIATION	Concomitant Chemoradiotherapy (Stupp backbone)	Intensity-modulated radiotherapy (IMRT) 60 Gy in 30 fractions (2 Gy/fx, 5 fx/week). Oral temozolomide 75 mg/m² daily, starting on the first day of RT and continuing until the last fraction (≈ 42-49 days). Adjuvant Temozolomide begins 4 weeks after completion of RT: 150 mg/m² PO days 1-5 of a 28-day cycle; escalate to 200 mg/m² cycle 2 if ANC ≥ 1.5 and platelets ≥ 100 × 10⁹/L. Six cycles total.
DRUG	Preventive Intrathecal Thiotepa	10 mg thiotepa once weekly for 6 consecutive weeks, beginning within 7 days of the first RT fraction. Lumbar puncture or injection via intra-operatively placed Ommaya reservoir.

Timeline

• Start date: 2026-01-04
• Primary completion: 2028-01-04
• Completion: 2029-01-04
• First posted: 2026-04-06
• Last updated: 2026-04-06

Locations

1 site across 1 country: China