Efficacy of Zoster Vaccination in Glioblastoma Patients (STARGATE)

Herpes Zoster Vaccine and Autologous CMV-specific T Cells as an Immunomodulatory Adjunct to Standard Neurosurgical Resection Radiochemotherapy in Glioblastoma

In modern practice a trimodality treatment has emerged as standard of care for histologically confirmed glioblastoma.

We hypothesize that the additional vaccination against herpes zoster, after surgical resection followed by irradiation therapy and chemotherapy of patients with glioblastoma will lead to a superior local control, overall and progression free survival. In an additional experimental setting based on patient preference the immunological effectiveness of the adoptive transfer of autologous polyclonal cytomegalovirus (CMV) specific T cells will be examined.

Study Overview

• Status: Not yet recruiting
• Conditions: Glioblastoma (GBM)
• Intervention / Treatment: Other: Standard of care treatment without additional vaccination; Biological: Additional vaccination against shingles (herpes zoster)

Detailed Description

This multicenter study investigates novel immunomodulatory strategies in patients with histologically confirmed glioblastoma undergoing microsurgical resection at initial diagnosis.

In the randomized intervention arm, patients receive an EMA-approved, inactivated herpes zoster vaccine postoperatively, followed by standard radiotherapy or radiochemotherapy according to ESTRO/EANO guidelines. In a patient-preference experimental arm, the same regimen is combined with autologous CMV-specific T-cell adoptive transfer.

The control group undergoes neurosurgical resection and standard-of-care radiotherapy, with or without temozolomide, without additional herpes zoster vaccination or CMV-specific T-cell therapy.

Primary endpoint is overall survival (OS), while secondary endpoints include progression-free survival (PFS) and local tumor control, immunological response, safety, and tolerability. Exploratory endpoints incorporate patient-reported outcome measures (PROMs), assessing quality of life, cognitive function, and treatment-related symptoms. Interventions are delivered from surgical resection through completion of radiochemotherapy. We hypothesize that herpes zoster vaccination will improve survival and local tumor control, while adoptive CMV-specific T-cell therapy will provide additional immunotherapeutic benefit in this refractory glioblastoma population.

• Study Type: Interventional
• Enrollment (Estimated): 230
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Prof. Dr.med. Guberina; Phone Number: +492017232054; Email: strahlentherapie@uk-essen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Subjects must meet all of the following inclusion criteria to be eligible for enrolment into the trial:

• At least 18 years of age
• Written informed consent of the subject
• Life expectancy at least 3 months
• Participants of child-bearing age must use effective contraception
• Indication for definitive radiotherapy of glioblastoma or adjuvant radiation therapy of glioblastoma resection cavity according to interdisciplinary tumor board consensus and after radiation oncologists evaluation
• Histopathologically proven glioblastoma
• Incorporation of pre-neurochirurgical /-treatment PET/CT or/ and PET/MRI findings into the radiation therapy plan if patient undergoes PET/CT or/ and PET/MRI

Exclusion Criteria:

Subjects will not be included in the study if any of the following criteria apply. General Exclusion Criteria:

• Subjects not able to give consent
• Subject without legal capacity who is unable to understand the nature, scope, significance, and con- sequences of this clinical trial
• Simultaneously participation in another clinical trial or participation in any clinical trial involving ad- ministration of an investigational medicinal product within 30 days prior to clinical trial beginning
• Subjects with a physical or psychiatric condition which at the investigator's discretion may put the subject at risk may confound the trial results or may interfere with the subject's participation in this clinical trial
• Known or persistent abuse of medication, drugs or alcohol
• Contraindications for radiotherapy (including active inflammatory disease)
• Known hypersensitivity against vaccine contra herpes zoster, or its constituents
• Gliomatosis cerebri at time of enrollment on any imaging or proved by histopathology
• Synchronous secondary malignancy

Exclusion criteria regarding special restrictions for females as the treatment procedures require the highest degree of safety for the child:

• Current or planned pregnancy or nursing women
• Females of child-bearing potential, who are not using and not willing to use medically reliable methods of contraception for the entire study duration (such as oral, injectable, or implantable contracep- tives, or intrauterine contraceptive devices) unless they are surgically sterilized / hysterectomized or there are any other criteria considered sufficiently reliable by the investigator in individual cases

Indication-specific exclusion criteria in order to guarantee the highest degree of safety of all treatment procedures from a medical point of view:

• Primary infra-tentorial located glioblastoma (justification: specific subgroup of patients with different prognosis)

• Significant comorbidities at baseline, which would prevent possible chemotherapy, including:

  i. Platelet count < 100/nl ii. Absolute neutrophil count (ANC) < 1.5/nl iii. AST or ALT > 3 times the upper limit of normal iv. Total bilirubin above the normal range v. Serum creatinine > 1.7 mg/dl

• Patients with clinically significant liver-, renal- or blood disorder
• Patients with known additional significant neurological disease (e.g. primary seizure disorder*, de-mentia, progressive degenerative neurological disease, meningitis or encephalitis, hydrocephalus with increased intracranial pressure)
• Patients with brain tumor-related epilepsy, seizure-free under antiepileptic therapy are eligible
• Active implanted medical device (e.g. deep brain stimulators, spinal cord stimulators, vagus nerve stimulators, pacemakers, defibrillators and programmable shunts) or documented clinically signifi- cant arrhythmias
• History of HIV infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A Control Group, standard of care trimodality treatment (neurosurgical resection + R(C)Tx); Standard of care trimodality treatment (neurosurgical resection + R(C)Tx) without additional vaccination	Other: Standard of care treatment without additional vaccination; Standard of care treatment without additional vaccination
Experimental: Arm B, interventional arm, trimodality treatment and vaccination against herpes zoster; Trimodality treatment and vaccination against herpes zoster	Biological: Additional vaccination against shingles (herpes zoster); Based on patient-preference patients receive autologous CMV-specific T-cells additionally to vaccination contra herpes zoster after completion of radio(chemo-)therapy. Patients included in the experimental arm shall be HLA typed. Up to 6 intravenous infusions of in vitro-expanded T cells at a dose of 2 × 107 cells/m2 body surface area every 2 to 4 weeks shall be administered after clinical assessment. Patients shall continue standard-of-care treatment with temozolomide if indicated. Where possible, administration of autologous T-cells shall be scheduled to fall between chemotherapy treatment weeks to avoid concurrent infusions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall Survival	Overall survival defined as time from neurosurgical resection to death of any cause. Study time per subject from enrollment through the end of treatment after a maximum of 12 months (provided that additional CTx consolidation therapy is administered)
Overall survival	From enrollment through the end of treatment after a maximum of 12 months (provided that additional CTx consolidation therapy is administered)

Collaborators and Investigators

• Sponsor: University Hospital, Essen
• Collaborators: Karolinska Institutet; Leiden University Medical Center; Universitätsklinikum Hamburg-Eppendorf

Study record dates

Study Major Dates

• Study Start (Estimated): January 2, 2027
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: April 16, 2026
• First Submitted That Met QC Criteria: April 16, 2026
• First Posted (Actual): April 23, 2026

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 16, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: 25-12859-BO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No