Pharmacoscopy for Patients With Refractory Primary Brain Tumors (EViDENCE-BT)

Advanced technology of ex vivo drug profiling referred to as pharmacoscopy may allow to identify novel drugs for the treatment of glioblastoma and other refractory brain tumors at an individual patient level. This personalized therapeutic approach was developed and validated in pre-clinical glioma models. With the current research proposal, we seek to establish feasibility for a clinical interventional trial for patients with refractory primary brain tumors that is based on pharmacoscopy-guided selection of treatment.

The study is supported by an unrestricted grant from Anti Cancer Fund.

Study Overview

• Status: Not yet recruiting
• Conditions: Glioma; Glioblastoma; Ependymoma; Medulloblastoma; Meningioma; Brain (Nervous System) Cancers; Rare Primary Brain Tumors; Rare CNS Primary Tumors
• Intervention / Treatment: Device: Pharmacoscopy 1.0

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Michael Weller, Prof. Dr. med.; Phone Number: +41442555500; Email: EViDENCE-BT@usz.ch

Study Locations

• Switzerland
  • Basel-Landschaft
    • Basel, Basel-Landschaft, Switzerland, 4021
      • University Hospital Basel
      • Contact: Gregor Hutter, Prof. Dr. med.; Phone Number: +41612657124; Email: Gregor.Hutter@usb.ch
  • Canton of St. Gallen
    • Sankt Gallen, Canton of St. Gallen, Switzerland, 9007
      • Cantonal Hospital St Gallen
      • Contact: Marian Neidert, PD Dr. med.; Phone Number: +41714941199; Email: marian.neidert@kssg.ch
  • Canton of Zurich
    • Zurich, Canton of Zurich, Switzerland, 8091
      • University Hospital Zurich
      • Contact: Emilie Le Rhun, PD Dr med; Phone Number: +41442553899; Email: EViDENCE-BT@usz.ch

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 18 years or older on day of signing informed consent, female or male.
2. Refractory glioblastoma, isocitrate dehydrogenase (IDH)-mutant astrocytoma or oligodendroglioma, histone-mutant glioma, ependymoma, medulloblastoma, meningioma or other rare primary brain tumor with a histological confirmation according to the WHO classification 2021. Primary tumors can be located at the cerebral or spinal level. Primary brain tumors with metastases outside of the brain may also be considered.
3. Karnofsky performance status of 60 or more
4. Life expectancy >12 weeks.
5. Limited systemic therapeutic options as per treating physician judgement. The number of previous lines of therapies is not limited.
6. Surgery clinically indicated. A histological confirmation of the diagnosis of a recurrent brain tumor will be required before any treatment can be initiated.
7. Adequate bone marrow, renal and hepatic function
8. Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and return for the required assessments.
9. Written informed consent for study participation must be signed and dated by the patient and the investigator prior to any study-related intervention.

Exclusion Criteria:

1. Inability to undergo brain or spine MRI.
2. Concurrent treatment with other systemic tumor-directed pharmacotherapies.
3. Intent to be treated with radiotherapy.
4. Any investigational antitumor therapy other than those under investigation in this study.
5. Judgment by the investigator that the patient should not participate in the study because the patient is unlikely to comply with study procedures, restrictions and requirements.
6. Intention to become pregnant during the course of the study or pregnancy. Women of childbearing potential, including women who had their last menstruation in the last 2 years, must have a negative urinary or serum pregnancy test.
7. Women who are breast feeding and who do not agree to discontinue nursing prior to the first study treatment and for the period defined in the protocol.
8. Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: All patients will have their tumor analyzed by pharmacoscopy.; Therapeutic decisions will be taken considering the results of the pharmacoscopy analysis, and also standard histopathological and molecular analysis, including next generation sequencing, molecular profiling analysis as available, characteristics of the patient and previous treatments received.	Device: Pharmacoscopy 1.0; The intervention is the submission of freshly obtained surgical material to ex vivo drug profiling which we term pharmacoscopy (PCY). The performance study is interventional as the test results shall influence patient management decisions and/or may be used to guide treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To demonstrate the overall feasibility of pharmacoscopy-guided treatment for patients with refractory primary brain tumors	The feasibility is defined as: 80% success rate of generating a pharmacoscopy result within 10 days of surgery (32/40 patients), 50% success rate of placing patients on selected drug based on pharmacoscopy (16/32 patients).	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To explore the efficacy of pharmacoscopy-guided treatment - 1	(1) Response rate	12 months
To explore the efficacy of pharmacoscopy guided treatment - 2	duration of response	12 months
To explore the efficacy of pharmascopy guided treatment - 3	progression-free survival	12 months
To explore the efficacy of pharmascopy guided treatment - 4	overall survival	24 months
To confirm the safety and tolerability of treatment selected based on pharmacoscopy - 1	Neurological function (NANO scale, Nayak et al. 2017)	12 months
To confirm the safety and tolerability of treatment selected based on pharmacoscopy -2	Karnofsky performance status (score 0-100)	12 months
To confirm the safety and tolerability of treatment selected based on pharmacoscopy - 3	Steroid use (dose in mg equivalent dexamethasone)	12 months
Quality of life -1	EORTC QLQ C30 auto-questionnaire	12 months
Quality of life - 2	EORTC BN20 autoquestionnaire	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Translational research	prospective assessement of the value of liquid biopsy in parallel of imaging assessment	12 months

Collaborators and Investigators

• Sponsor: University of Zurich
• Collaborators: University Hospital, Basel, Switzerland; University Hospital, Zürich; Cantonal Hospital of St. Gallen

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): September 15, 2028
• Study Completion (Estimated): September 15, 2028

Study Registration Dates

• First Submitted: December 17, 2024
• First Submitted That Met QC Criteria: January 27, 2025
• First Posted (Actual): February 3, 2025

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: personalized medicine; drug repurposing; drug testing; pharmacoscopy; refractory tumor
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Neuroectodermal Tumors, Primitive; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neoplasms; Neurologic Manifestations; Glioblastoma; Glioma; Meningioma; Ependymoma; Medulloblastoma
• Other Study ID Numbers: EViDENCE-BT

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