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Ex Vivo Drug response Evaluation for Next generation Care of Brain Metastases

Status
Recruiting
Cancer types
Brain metastases
Trial phase
2

Funding

€ 496 000
ACF funding

Why this trial

Cancer that has spread to the brain is very difficult to treat. Despite improvements in screening and therefore earlier detection, the outcome for cancer patients with brain metastasis remains poor, with a median survival limited to only 6 months. 1

Traditionally, brain metastases are treated with surgery and local radiotherapy. However, it’s becoming increasingly clear that cancer that has spread to the brain can also respond to systemic drug treatments which target the entire body, like chemotherapy. 2

Unfortunately, systemic drug treatment has its limitations, caused by the many variations in a tumour and the tissues around it. 3,4,5 Another issue is that many drugs are unable to effectively reach the brain metastases.

Within a single patient, cancer cells show DNA-variations that drive their growth, spread, and resistance to (drug) therapies. These variations might explain why a treatment works differently depending on the location of the metastasis.

Not much is known about how drugs behave in brain metastases or how effective they are there. On top of that, many cancer patients have already gone through several treatments before brain metastases are found, which can make the cancer cells more resistant to new treatments and limit the number of options available.

Right now, predictions about which drugs might work are based on analysing small parts of the original tumour. However, with brain metastases, it's important to analyse the metastatic cells as well, since these metastases can have different characteristics that affect how they respond to treatments. 

New approaches for the treatment of brain metastases are thus urgently needed.

Why this intervention

One of the new approaches is pharmacoscopy, a cutting-edge technology that tests hundreds of drugs on small tumour samples taken from individual cancer patients. It can actually see what each drug does to each cell.

This novel technology was developed by the Snijder Lab at the Federal Institute of Technology in Zurich (ETH). Samples of the tumour are removed during surgery, and >100 drugs or drug-combinations are then tested on it. This helps to predict which drugs might work best for each individual patient 6,7.

Trial design

This is a 3:1 randomised trial on the pharmacoscopy-guided approach. 102 patients will be assigned to either the Pharmacoscopy arm (80 patients) or the control arm (22 patients).

Arm 1 - Pharmacoscopy:

For patients randomised to the pharmacoscopy-guided arm, tumour samples will be collected during the planned surgery for brain metastasis.

These samples will be sent to the lab for pharmacoscopy analysis.

The same drug panel will be tested for all patients and throughout the trial. The results of the pharmacoscopy analysis will be discussed with the investigator and the tumour board, and treatment will be determined based on these findings.

Arm 2 - Standard treatment:

For patients randomised to the control arm, tumour samples will also be collected during the surgery for brain metastasis. Their treatment options will be discussed with the investigator and the tumour board.

The trial will run in Switzerland.

Partners

Researchers

Dr. med. Emilie Le Rhun

Department of Medical Oncology and Hematology

University Hospital and University of Zurich

Frauenklinikstrasse 10, 8091 Zurich

 

Prof. Dr. Berend Snijder

Institute of Molecular Systems Biology

Federal Institute of Technology (ETH) Zurich

Otto-Stern-Weg 3, 8093 Zurich

 

Sponsor

Prof. Dr. med. Michael Weller

Department of Neurology

University Hospital and University of Zurich

Frauenklinikstrasse 26, 8091 Zurich

 

References

  1. Steindl, Ariane, Tabea J. Brunner, Kira Heimbach, Katharina Schweighart, Georg M. Moser, Helena M. Niziolek, Elisabeth Moor, et al. 2022. “Changing Characteristics, Treatment Approaches and Survival of Patients with Brain Metastasis: Data from Six Thousand and Thirty-One Individuals over an Observation Period of 30 Years.” European Journal of Cancer (Oxford, England: 1990) 162 (February): 170–81. https://doi.org/10.1016/j.ejca.2021.12.005.
  2. Le Rhun, E., M. Guckenberger, M. Smits, R. Dummer, T. Bachelot, F. Sahm, N. Galldiks, et al. 2021. “EANO-ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up of Patients with Brain Metastasis from Solid Tumours.” Annals of Oncology: Official Journal of the European Society for Medical Oncology 32 (11): 1332–47.
  3. Priedigkeit, Nolan, Ryan J. Hartmaier, Yijing Chen, Damir Vareslija, Ahmed Basudan, Rebecca J. Watters, Roby Thomas, et al. 2017. “Intrinsic Subtype Switching and Acquired ERBB2/HER2 Amplifications and Mutations in Breast Cancer Brain Metastases.” JAMA Oncology 3 (5): 666–71. https://doi.org/10.1001/jamaoncol.2016.5630.
  4. Li, Meichen, Xue Hou, Ke Sai, Lihong Wu, Jing Chen, Baishen Zhang, Na Wang, et al. 2022. “Immune Suppressive Microenvironment in Brain Metastatic Non-Small Cell Lung Cancer: Comprehensive Immune Microenvironment Profiling of Brain Metastases versus Paired Primary Lung Tumors (GASTO 1060).” Oncoimmunology 11 (1): 2059874. https://doi.org/10.1080/2162402X.2022.2059874.
  5. Friebel, Ekaterina, Konstantina Kapolou, Susanne Unger, Nicolás Gonzalo Núñez, Sebastian Utz, Elisabeth Jane Rushing, Luca Regli, et al. 2020. “Single-Cell Mapping of Human Brain Cancer Reveals Tumor-Specific Instruction of Tissue-Invading Leukocytes.” Cell 181 (7): 1626-1642.e20. https://doi.org/10.1016/j.cell.2020.04.055.
  6. Snijder, Berend, Gregory I. Vladimer, Nikolaus Krall, Katsuhiro Miura, Ann-Sofie Schmolke, Christoph Kornauth, Oscar Lopez de la Fuente, et al. 2017. “Image-Based Ex-Vivo Drug Screening for Patients with Aggressive Haematological Malignancies: Interim Results from a Single-Arm, Open-Label, Pilot Study.” The Lancet. Haematology 4 (12): e595–606. https://doi.org/10.1016/S2352-3026(17)30208-9.
  7. Kornauth, Christoph, Tea Pemovska, Gregory I. Vladimer, Günther Bayer, Michael Bergmann, Sandra Eder, Ruth Eichner, et al. 2022. “Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematologic Cancers and Identifies Exceptional Responders.” Cancer Discovery 12 (2): 372–87. https://doi.org/10.1158/2159-8290.CD-21-0538.

Our role

Financial support

Why we support this trial

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Funding

€ 496 000
ACF funding

Questions about participation? emilie.lerhun@usz.ch Questions about this trial? Anticancer Fund studies@anticancerfund.org

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References

  1. Steindl, Ariane, Tabea J. Brunner, Kira Heimbach, Katharina Schweighart, Georg M. Moser, Helena M. Niziolek, Elisabeth Moor, et al. 2022. “Changing Characteristics, Treatment Approaches and Survival of Patients with Brain Metastasis: Data from Six Thousand and Thirty-One Individuals over an Observation Period of 30 Years.” European Journal of Cancer (Oxford, England: 1990) 162 (February): 170–81. https://doi.org/10.1016/j.ejca.2021.12.005.
  2. Le Rhun, E., M. Guckenberger, M. Smits, R. Dummer, T. Bachelot, F. Sahm, N. Galldiks, et al. 2021. “EANO-ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up of Patients with Brain Metastasis from Solid Tumours.” Annals of Oncology: Official Journal of the European Society for Medical Oncology 32 (11): 1332–47.
  3. Priedigkeit, Nolan, Ryan J. Hartmaier, Yijing Chen, Damir Vareslija, Ahmed Basudan, Rebecca J. Watters, Roby Thomas, et al. 2017. “Intrinsic Subtype Switching and Acquired ERBB2/HER2 Amplifications and Mutations in Breast Cancer Brain Metastases.” JAMA Oncology 3 (5): 666–71. https://doi.org/10.1001/jamaoncol.2016.5630.
  4. Li, Meichen, Xue Hou, Ke Sai, Lihong Wu, Jing Chen, Baishen Zhang, Na Wang, et al. 2022. “Immune Suppressive Microenvironment in Brain Metastatic Non-Small Cell Lung Cancer: Comprehensive Immune Microenvironment Profiling of Brain Metastases versus Paired Primary Lung Tumors (GASTO 1060).” Oncoimmunology 11 (1): 2059874. https://doi.org/10.1080/2162402X.2022.2059874.
  5. Friebel, Ekaterina, Konstantina Kapolou, Susanne Unger, Nicolás Gonzalo Núñez, Sebastian Utz, Elisabeth Jane Rushing, Luca Regli, et al. 2020. “Single-Cell Mapping of Human Brain Cancer Reveals Tumor-Specific Instruction of Tissue-Invading Leukocytes.” Cell 181 (7): 1626-1642.e20. https://doi.org/10.1016/j.cell.2020.04.055.
  6. Snijder, Berend, Gregory I. Vladimer, Nikolaus Krall, Katsuhiro Miura, Ann-Sofie Schmolke, Christoph Kornauth, Oscar Lopez de la Fuente, et al. 2017. “Image-Based Ex-Vivo Drug Screening for Patients with Aggressive Haematological Malignancies: Interim Results from a Single-Arm, Open-Label, Pilot Study.” The Lancet. Haematology 4 (12): e595–606. https://doi.org/10.1016/S2352-3026(17)30208-9.
  7. Kornauth, Christoph, Tea Pemovska, Gregory I. Vladimer, Günther Bayer, Michael Bergmann, Sandra Eder, Ruth Eichner, et al. 2022. “Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematologic Cancers and Identifies Exceptional Responders.” Cancer Discovery 12 (2): 372–87. https://doi.org/10.1158/2159-8290.CD-21-0538.
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