Glioblastoma (GBM)Phase 2PRISMNCT07511725
Prophylactic Regimen With Intrathecal Thiotepa in SVZ-positive or Meningeal-risk Glioblastoma
A Phase 2 study testing Maximal surgical resection, Concomitant Chemoradiotherapy (Stupp backbone) and Preventive Intrathecal Thiotepa in people with Glioblastoma (GBM), run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Glioblastoma (GBM)
- What is being tested?
- Maximal surgical resection, Concomitant Chemoradiotherapy (Stupp backbone) and Preventive Intrathecal Thiotepa
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteChina
- Study dates
- 4 Jan 2026to 4 Jan 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- Pre-operative MRI showing tumour in direct contact with the lateral ventricular sub-ventricular zone (SVZ+); OR
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
2nd Affiliated Hospital, School of Medicine
Hangzhou, Zhejiang, 310000
Ting Zhang, phD, 057187783521, zezht@zju.edu.cn
zezht@zju.edu.cn
About this study
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）
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?
Read more
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.
Read the 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:
- pre-operative MRI showing tumor in direct contact with the sub-ventricular zone (SVZ+), or
- 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)
- Being tested
- Maximal surgical resection, Concomitant Chemoradiotherapy (Stupp backbone), Preventive Intrathecal Thiotepa
- Keywords
- Prophylactic Intrathecal chemotherapy, thiotepa, ventricular invasion, ventricular entry
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Maximal surgical resectionProcedure or surgery
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.
Concomitant Chemoradiotherapy (Stupp backbone)Radiation
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.
Preventive Intrathecal ThiotepaDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Stupp plus intrathecal injection of thiotepa | Experimental | preventive thiotepa injections 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. Receives: Procedure: Maximal surgical resection; Radiation: Concomitant Chemoradiotherapy (Stupp backbone); Drug: Preventive Intrathecal Thiotepa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Leptomeningeal-metastasis-free survival (LMFS)
Kaplan-Meier estimate of the distribution of time without LM; primary efficacy endpoint.
Measured: From first intrathecal thiotepa injection until documented leptomeningeal metastasis (radiologic or cytologic) or death from any cause, assessed up to 24 months.
Secondary outcomes (3)
Overall survival
Time from treatment initiation until death
Measured: 3 months,6 months and 1 year after treatment
Progression-free survival
Time from treatment initiation until disease progression( RECIST1.1 )
Measured: 3 months,6 months and 1 year after treatment
Safety assessment
Incidence and severity of treatment-related adverse events using CTCAE 5.0.
Measured: From informed consent until 30 days after last protocol therapy (≈ 9 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2026
- Study start4 Jan 2026
- Primary completion4 Jan 2028 (estimated)
- Study completion4 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma (GBM)Studies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital, Zhejiang University, School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07511725
- Sponsor's protocol ID
- Y2025-1643
- Acronym
- PRISM
- Status last verified
- Dec 2025
- First submitted
- 30 Mar 2026
- Last updated
- 6 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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）
- ClinicalTrials.gov ID
- NCT07511725
- Acronym / sponsor ID
- PRISM / Y2025-1643
- Conditions
- Glioblastoma (GBM)
- Keywords
- Prophylactic Intrathecal chemotherapy, thiotepa, ventricular invasion, ventricular entry
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 38 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Study start
- 4 Jan 2026 (actual)
- Primary completion
- 4 Jan 2028 (estimated)
- Study completion
- 4 Jan 2029 (estimated)
- First posted
- 6 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- pre-operative MRI showing tumor in direct contact with the sub-ventricular zone (SVZ+), or
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Stupp plus intrathecal injection of thiotepa | Experimental | Procedure: Maximal surgical resection, Radiation: Concomitant Chemoradiotherapy (Stupp backbone), Drug: Preventive Intrathecal Thiotepapreventive thiotepa injections 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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:
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2 and estimated life expectancy ≥ 3 months.
- Neurological symptoms stable for ≥ 7 days before enrollment.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Maximal surgical resectionMaximal-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. | Procedure or surgery | Stupp plus intrathecal injection of thiotepa |
| 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. | Radiation | Stupp plus intrathecal injection of thiotepa |
| Preventive Intrathecal Thiotepa10 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. | Drug | Stupp plus intrathecal injection of thiotepa |
Primary outcome
Leptomeningeal-metastasis-free survival (LMFS)
Time frame: From first intrathecal thiotepa injection until documented leptomeningeal metastasis (radiologic or cytologic) or death from any cause, assessed up to 24 months.
Kaplan-Meier estimate of the distribution of time without LM; primary efficacy endpoint.
3 secondary outcomes
Overall survival
Time frame: 3 months,6 months and 1 year after treatment
Progression-free survival
Time frame: 3 months,6 months and 1 year after treatment
Safety assessment
Time frame: From informed consent until 30 days after last protocol therapy (≈ 9 months)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Maximal surgical resection, Concomitant Chemoradiotherapy (Stupp backbone) and Preventive Intrathecal Thiotepa in people with Glioblastoma (GBM), run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ting Zhang, phD. (+86-571-87783521, zezht@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Leptomeningeal-metastasis-free survival (LMFS) (time frame: From first intrathecal thiotepa injection until documented leptomeningeal metastasis (radiologic or cytologic) or death from any cause, assessed up to 24 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2026.