Preventive intrathecal thiotepa with standard chemoradiation for high‑risk glioblastoma
Official title: A Pilot Study of Prophylactic Intrathecal Thiotepa Plus the Stupp Regimen for Glioblastoma With Subventricular Zone Contact or Intraoperative Ventricular Entry(PRISM-Trial)
Run by Second Affiliated Hospital, Zhejiang University, School of Medicine · NCT07511725 · Data updated 2026-11-12
This trial tests whether adding six weekly intrathecal injections of thiotepa to standard chemoradiation can lower leptomeningeal spread and improve outcomes for adults with newly diagnosed GBM that contacts the subventricular zone or had ventricular entry during surgery.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Enrollment | 38 (estimated) |
| Sponsor | Second Affiliated Hospital, Zhejiang University, School of Medicine Academic / other |
| Drugs / interventions | chemotherapy, methotrexate |
| Locations | 1 site (Hangzhou, Zhejiang) |
| Status | Recruiting |
| Started | January 4, 2026 |
| Main results expected | January 4, 2028 |
| Study ends | January 4, 2029 |
| Registry record updated | April 6, 2026 |
| Trial ID | NCT07511725 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Ideal candidates are adults 18–75 years with newly diagnosed WHO grade 4 IDH‑wildtype glioblastoma who have tumor contact with the subventricular zone or documented intraoperative ventricular entry, have ECOG 0–2, and meet standard hematologic, hepatic, and renal criteria.
✕Probably not a fit
Patients with recurrent GBM, tumors not contacting the SVZ and without ventricular entry, those with poor performance status, severely abnormal labs, or contraindications to intrathecal therapy are unlikely to benefit from this protocol.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
This is a single‑arm, prospective phase II trial giving six weekly 10 mg intrathecal doses of thiotepa during the standard Stupp chemoradiotherapy for adults with newly diagnosed WHO grade 4, IDH‑wildtype glioblastoma who are at high risk for leptomeningeal metastasis because their tumor touches the subventricular zone or there was intraoperative ventricular entry. Thiotepa is delivered by lumbar puncture or Ommaya reservoir starting within one week of radiotherapy initiation while patients receive 60 Gy/30 fractions with daily temozolomide. The main outcome is freedom from leptomeningeal metastasis at one year, with secondary endpoints of overall survival, progression‑free survival, and safety/tolerability compared with historical controls. The approach is intended as a prophylactic intervention given when circulating tumor cell burden is expected to be low.
Why it matters
Potential benefit: If successful, the regimen could reduce the risk of leptomeningeal metastasis and extend progression‑free and overall survival in this high‑risk GBM subgroup.
How similar studies have gone: Intrathecal thiotepa has prior use for leptomeningeal disease in other cancers and case series report activity against meningeal glioma deposits, but using it prophylactically in newly diagnosed high‑risk GBM is largely novel and not yet validated in randomized trials.
Who can join: the full rules
Show full inclusion / exclusion criteria
Inclusion Criteria: * Age 18-75 years, either sex. * Histologically confirmed newly-diagnosed WHO grade IV glioblastoma with at least one measurable lesion on MRI. * Must fulfil ONE of the following high-risk imaging/surgical conditions: 1. Pre-operative MRI showing tumour in direct contact with the lateral ventricular sub-ventricular zone (SVZ+); OR 2. Operative record and post-operative imaging documenting an intra-operative cerebro-spinal-fluid leak (ventricular entry, VE). * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 and estimated life expectancy ≥ 3 months. * Neurological symptoms stable for ≥ 7 days before enrollment. * Adequate bone-marrow reserve: neutrophils ≥ 1.5 × 10⁹/L, haemoglobin ≥ 90 g/L, platelets ≥ 75 × 10⁹/L. * Coagulation acceptable: PT/INR and aPTT ≤ 1.5 × upper limit of normal (ULN). Hepatic: total bilirubin ≤ 1.5 × ULN, ALT \& AST ≤ 1.5 × ULN, albumin ≥ 30 g/L. Renal: serum creatinine ≤ 2 × ULN and calculated or 24-h creatinine clearance ≥ 50 mL/min. * Reliable contraception from first dose until 3 months after the last dose for both sexes. Exclusion Criteria: * Pregnant or lactating women. * Active infection requiring intravenous antibiotics within 7 days before study entry, or therapeutic anticoagulation with warfarin. * History of any other malignancy within the previous 5 years (except adequately treated basal-cell carcinoma of skin or cervical carcinoma in-situ). * Known HIV infection, AIDS, immunodeficiency syndromes, or active autoimmune disease needing systemic therapy. * Severe medical, neurological or psychiatric conditions that would preclude compliance with protocol procedures. * Disrupted ventricular drainage catheter or anatomical contraindication preventing safe lumbar puncture or Ommaya reservoir placement. * Uncontrolled chronic illnesses: diabetes, congestive heart failure (NYHA III/IV), hepatic cirrhosis, chronic kidney disease stage ≥ 3b, etc. * Any condition judged by the investigator to increase the risks of intrathecal chemotherapy or to confound toxicity assessment.
Where it's running
-
2nd Affiliated Hospital, School of Medicine
Hangzhou, Zhejiang, China Recruiting
Study contacts
- Study coordinator: Ting Zhang, phD.
- Email: zezht@zju.edu.cn
- Phone: +86-571-87783521
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How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.