Vortioxetine for Newly Diagnosed Glioblastoma

NCT ID: NCT07284628

Last Updated: 2025-12-16

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-15
• Study Completion Date: 2029-06-30

Brief Summary

There is a very urgent need to improve on the currently limited treatment options for patients with glioblastoma. Despite extensive knowledge on the molecular pathogenesis of glioblastoma obtained through genomic, transcriptional and proteomic profiling, targeted therapy efforts have not yielded major advances, likely because of interindividual and intraindividual tumor heterogeneity and redundant oncogenic pathway activation.

Accordingly, there is a strong rationale to approach the challenge of glioblastoma from a different angle, e.g., by ex vivo drug sensitivity profiling which is agnostic to the molecular profile of a tumor. This approach that we have termed "pharmacoscopy", has previously been explored in liquid cancers and probably led to improved patient outcomes. Using pharmacoscopy, the antidepressant drug, vortioxetine, has been identified as a lead candidate for further exploration in patients with glioblastoma. Vortioxetine also demonstrated synergistic anti-glioma activity in combination with temozolomide or lomustine.

The ReVoGlio trial aims at demonstrating that vortioxetine, a drug selected based on ex vivo drug profiling (pharmacoscopy), is of benefit for patients with newly diagnosed glioblastoma.

Conditions

Glioblastoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vortioxetine in addition to the standard of care

Group Type: EXPERIMENTAL

Vortioxetine

Intervention Type: DRUG

Vortioxetine will be added to standard of care temozolomide chemoradiotherapy for patients with newly diagnosed glioblastoma

Interventions

Vortioxetine

Vortioxetine will be added to standard of care temozolomide chemoradiotherapy for patients with newly diagnosed glioblastoma

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male or female, age ≥18 years

2. Patients with histologically confirmed newly diagnosed glioblastoma per CNS WHO 2021 classification

3. O6-methylguanine DNA methyltransferase (MGMT) promotor methylation status known or tissue available for testing

4. Karnofsky performance status (KPS) ≥ 70%

5. Intent to treat with standard radiochemotherapy per EANO guidelines (radiotherapy will 60 Gy in 1.8-2 Gy fractions. Concomitant chemotherapy with temozolomide (75 mg/m2 daily throughout radiotherapy, including at weekends) followed by six cycles of maintenance temozolomide (150-200 mg/m2, 5 out of 28 days). Short course radiotherapy at 40 Gy is not allowed.

6. Female patients must be either documented not to be Women of Childbearing Potential (WOCBP) or must have a negative pregnancy test within 14 days of starting treatment. Additionally WOCBP must agree to use, from the screening to 6 months following the last study drug administration, highly effective contraception methods, as defined by the "Recommendations for contraception and pregnancy testing in clinical trials" issued by the Head of Medicine Agencies' Clinical Trial Facilitation Group (www.hma.eu/ctfg.html) and which include, for instance, progesterone-only or combined (estrogen- and progesterone-containing) hormonal contraception associated with inhibition of ovulation, intrauterine devices, intrauterine hormone-releasing systems, bilateral tubal occlusion or vasectomized partner. WOCBP are defined as females who have experienced menarche, are not postmenopausal (12 months with no menses without an alternative medical cause) and are not permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral oophorectomy, or bilateral salpingectomy).

7. Male subjects able to father children must agree to use two acceptable methods of contraception throughout the study and during 6 months following the last study drug administration (e.g., condom with spermicidal gel). Double-barrier contraception is required.

8. Personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.

9. Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.

Exclusion Criteria

1. Prior treatment for newly diagnosed glioblastoma except surgery. 2. Intent to be treated with tumor-treating fields. 3. Inability to undergo contrast-enhanced MRI. 4. Inadequate bone marrow, renal and hepatic function:

• Absolute neutrophil count (ANC) < 1.5 x 10.9/L; platelets < 100 x 10.9/L
• Hemoglobin (Hb) < 9.0 g/dl. Blood marrow values must be measured independently of transfusion.
• Chronically impaired renal function as indicated by creatinine clearance < 50 mL/min or serum creatinine > 1.5 upper limit of normal (ULN).
• Inadequate liver function (ALT, AST, ALP ≥ 2.5 x ULN) 9. Any severe concomitant condition which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol, in the opinion of the investigator.

10. Any contra-indication to vortioxetine. 11. Medically documented history of active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (e.g., risk of doing harm to self or others), or patients with active severe personality disorders.

12. Pregnancy or breast feeding. 13. Presence of active and uncontrolled infections or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study.

14. Concurrent malignancies unless the patient has been disease-free without intervention for at least one year.

15. Requirement of concurrent use of other anti-cancer treatments or agents other than study medication.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Zürich

OTHER

Sponsor Role: collaborator

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: collaborator

Cantonal Hospital of St. Gallen

OTHER

Sponsor Role: collaborator

Kantonsspital Aarau

OTHER

Sponsor Role: collaborator

Cantonal Hospital of Lucerne, Switzerland

UNKNOWN

Sponsor Role: collaborator

University of Zurich

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Michael Weller, Prof. Dr. med.

Role: CONTACT

ReVoGlio@usz.ch

+41 44 255 55 00

References

Lee S, Weiss T, Buhler M, Mena J, Lottenbach Z, Wegmann R, Sun M, Bihl M, Augustynek B, Baumann SP, Goetze S, van Drogen A, Pedrioli PGA, Penton D, Festl Y, Buck A, Kirschenbaum D, Zeitlberger AM, Neidert MC, Vasella F, Rushing EJ, Wollscheid B, Hediger MA, Weller M, Snijder B. High-throughput identification of repurposable neuroactive drugs with potent anti-glioblastoma activity. Nat Med. 2024 Nov;30(11):3196-3208. doi: 10.1038/s41591-024-03224-y. Epub 2024 Sep 20.

Reference Type: BACKGROUND

PMID: 39304781 (View on PubMed)

Other Identifiers

ReVoGlio

Identifier Type: -

Identifier Source: org_study_id