Vortioxetine for Newly Diagnosed Glioblastoma

ConditionGlioblastoma

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorUniversity of Zurich

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Male or female, age ≥18 years

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

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

Karnofsky performance status (KPS) ≥ 70%

Disqualifiers

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.

Trial design

Design model

Single group

Treatments tested in this trial

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

Treatment groups

78 Participants

are divided into 1 treatment group

Group A: Vortioxetine in addition to the standard of careExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

Progression-free survival (PFS)

PFS is defined as the time from registration until the first event of interest: progressive disease or death from any cause. Patients not having an event at the time of analysis and patients starting a new anticancer therapy in the absence of an event will be censored at the date of their last tumor assessment showing non-progression before starting a new treatment. The PFS will be determined locally per RANO 2.0 criteria

Time frame

through study completion for each patient, an average of 6 months

Secondary outcomes

Adverse events

All AE will be assessed according to CTCAE v5.0

Time frame

From date of randomization until 30 days after vortioxetine interruption

Overall survival (OS)

OS will be calculated from registration until death from any cause. Patients not experiencing an event will be censored at the last date they were known to be alive. OS will be assessed in relation to external control data.

Time frame

until death, an average of 17 months

Neurological function 1

measured by NANO scale

Time frame

through study completion for each patient, an average of 6 months

Neurological function 2

measured by the RANO seizure scale

Time frame

through study completion for each patient, an average of 6 months

Other outcomes

Prognostic role of extent of resection and residual tumor

Assessment of a statistical association between extent of surgical resection / residual tumor (measured in mm3) and outcome (survival)

Time frame

until death, an average of 17 months

Prognostic role of the G8 frailty index

Assessment of a statistical association between the G8 total score and outcome (survival)

Time frame

through study completion for each patient, an average of 6 months

Drug exposure

Plasmatic concentration of vortioxetine

Time frame

through study completion for each patient, an average of 6 months

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Zurich

Lead sponsor

University Hospital, Zürich

Collaborator

University Hospital, Basel, Switzerland

Collaborator

Cantonal Hospital of St. Gallen

Collaborator

Kantonsspital Aarau

Collaborator

Cantonal Hospital of Lucerne, Switzerland

Collaborator

Source ClinicalTrials.gov

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