Ex Vivo Drug Response Evaluation for Next Generation Care of Brain Metastases

Trial Title: Ex Vivo Drug Response Evaluation for Next Generation Care of Brain Metastases

NCT ID: NCT06620380

Condition: Brain Metastases
Brain Metastases, Adult

Conditions: Official terms:
Neoplasm Metastasis
Neoplasms, Second Primary
Brain Neoplasms

Study type: Interventional

Study phase: Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Intervention model description: Phase II interventional randomized non-comparative clinical study

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Device
Intervention name: Pharmacoscopy 1.0
Description: Pharmacoscopy is currently an academically developed platform. The study is designed to investigate the clinical performance of this academic platform. In the interventional arm, the best candidate agent defined by pharmascopy will be considered to guide the therapeutic decision for each patient.
Arm group label: Arm 1: experimental arm, Pharmacoscopy-guided treatment

Intervention type: Other
Intervention name: Control
Description: The next systemic treatment after surgery will be discussed, with the investigator and at the tumor board, considering also standard histopathological and molecular analysis, including next generation sequencing, molecular profiling analysis and previous treatments received
Arm group label: Arm 2: control arm

Summary: Pharmacoscopy refers to an ex vivo real-time drug sensitivity profiling platform that has been shown to be of value in the treatment of leukemia (Snijder et al. 2017) (Kornauth et al. 2022) and may help to identify novel treatment opportunities for brain tumors as well (Lee et al. 2022). The rationale for pharmacoscopy-based drug sensitivity testing on real-time patient biopsies or surgery material is multiple: measuring drug response and sensitivity directly in real-time patient material, overcomes the problem of limited molecular biomarkers for established targeted therapeutic options and can identify effective drugs even for non-targeted therapies such as chemotherapy. It can also identify hitherto unknown specific vulnerabilities of cancer cells. Furthermore, testing directly on patient material overcomes the limitations of patient-derived cell cultures, organoids, and patient xenografts, as their prolonged culture times risk cellular adaptations and clonal selection that alter drug sensitivity. Pharmacoscopy maintains the tumor cell composition, including bystander cells or tumor microenvironment, and limits cell culture to max 48 hours. Furthermore, pharmacoscopy measures drug responses on a single-cell and on a high-content level, uniquely allowing to measure the drug sensitivity of tumor cells, and allowing to compare it to the drug cytotoxicity on healthy cells from the same patient. This relative readout has previously been shown to be essential for the correct prediction of a clinical response in haematological malignancies (Snijder et al. 2017) (Kornauth et al. 2022). The aim of this study is to generate preliminary data regarding superiority of the personalized pharmacoscopy-guided approach compared to a standard non-pharmacoscopy-guided approach, in patients with brain metastases with an indication for surgery, and limited therapeutic systemic options according to the treating physician.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Patients must be 18 years or older on the day of signing the informed consent, female or male. - Patients must have a Karnofsky performance status of 60 or more - Patients must have limited systemic therapeutic options as per treating physician judgement. The number of previous lines of therapies is not limited. - Patients with a tumor with a targetable oncogenic driver mutation should have already been treated with a targeted agent and options must have been exhausted. - Patients must have a clinical indication for surgery for probable brain metastasis - Patients will be considered eligible for the study only if the diagnosis of brain metastasis has been histologically confirmed on the sample obtained during the surgery performed after signing the informed consent form for the trial. - Any type of primary cancer is allowed: breast cancer, lung cancer, melanoma, other cancers. Patients may have several primary cancers. - Patients must have adequate bone marrow, renal and hepatic function documented at screening before surgery - 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 - Patients must have the 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. - 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: - Patients with rapidly progressive systemic disease - Patients with inability to undergo brain MRI evaluation. - Patients with progressive parenchymal brain metastases with an indication for requiring whole brain radiotherapy after surgery. Focal brain radiotherapy after surgery is allowed. - Judgement by the investigator that the patient is unlikely to comply with study procedures, restrictions and requirements. - Intention to become pregnant during the course of the study. - Female who are pregnant. - Female who are breastfeeding and who do not agree to discontinue nursing prior to the first treatment initiated during the study. - Sexually active males and females of childbearing potential who are not willing to use an effective contraceptive method during the study. Male participants who do not agree not to donate sperm.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: University Hospital Basel

Address:
City: Basel
Country: Switzerland

Contact:
Last name: Gregor Hutter

Phone: +41 61 265 38 97
Email: Gregor.Hutter@usb.ch

Facility:
Name: Cantonal Hospital St Gallen

Address:
City: St Gallen
Country: Switzerland

Contact:
Last name: Marian Neidert

Phone: +41 71 494 11 11
Email: marian.neidert@kssg.ch

Facility:
Name: University Hospital Zurich

Address:
City: Zurich
Country: Switzerland

Contact:
Last name: Emilie Le Rhun

Phone: +41 44 255 38 99
Email: emilie.lerhun@usz.ch

Start date: January 2025

Completion date: June 2027

Lead sponsor:
Agency: University of Zurich
Agency class: Other

Source: University of Zurich

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06620380