Observational Study of Responses to Treatments in Advanced Central Nervous System (CNS) Tumors

Background:

Primary central nervous system (CNS) tumors grow in the brain and spinal cord. These tumors are rare, but they are difficult to treat and often fatal. SmartMatch is a new technology that tries to help find the best medicines for the particular tumor by testing how small pieces of surgically removed tumor tissue react to different drugs. The study team wants to see if SmartMatch can complete the analysis and generate a report within 21 days from the time of the surgery.

Objective:

To better understand CNS tumors so doctors can find better ways to treat them in the future.

Eligibility:

People aged 15 years and older with recurrent CNS tumors. Patient must already be scheduled for a surgery for the tumor at the NIH.

Design:

The study team will collect a small amount of tumor samples during the planned surgery. They may also use tumor samples from previous procedures. No new or additional procedures will be done for the purpose of this study.

The tumor samples will be sent to a lab for SmartMatch analysis. Once completed, the results will be shared with the patient and his/her local doctor. Together they can decide whether to incorporate the results into the treatment plan. It is important to know that the results may or may not be helpful.

There will only be one blood test for research. Blood and tissue samples collected may be used for additional analysis. Tumor tissue may be used to grow additional samples for further study. Participants will receive a pathology diagnosis and mutation profile generated by pathologists who specialize in CNS tumors.

The study team will seek updates on participant's health approximately every 6 months for 3 years. Tumor samples may also be collected from any additional surgery done at NIH during this time....

Study Overview

• Status: Recruiting
• Conditions: Brain Cancer; Gliomas; Recurrent CNS Tumors; IDH-wildtype Gliomas; IDH-mutant Gliomas; Rare CNS Tumor
• Intervention / Treatment: Other: Tumor sample collection

Detailed Description

Background:

• Primary central nervous system (CNS) tumors are uncommon and are mostly classified as rare diseases. Despite their low incidence, CNS cancers are associated with significant morbidity and mortality across all age groups.
• Treatment options for CNS tumors are limited, especially upon disease progression, largely due to the incomplete understanding of disease biology and the challenges in conducting clinical studies, given the rarity of these diseases.
• The traditional pathway for oncology drug development, involving several phases of clinical trials, can take many years to a decade and comes with a tremendously high financial cost. To overcome this challenge and speed up improving oncology patient care, drug repurposing has emerged as a useful approach.
• Real-time drug screening for rare brain tumors is advancing precision medicine by generating clinical trial concepts aimed at overcoming key challenges in brain tumor management. However, delayed turnaround times remain a significant limitation to their clinical utility.
• The Gujral lab at the Fred Hutchinson Cancer Center has developed SmartMatch, a cutting-edge artificial intelligence (AI)-driven system pharmacology-based platform to address the challenges in precision medicine. The platform allows the generation of drug response data using real-time tissue-based screening using freshly resected tumor or biopsy from a patient. The data collected is used to train a machine learning model, allowing precise prediction to a large panel of Food and Drug Administration (FDA)-approved drugs. This is a test that can be ordered by any physician in the US, and results are available upon request.

Objective:

-To determine the proportion of participants with advanced CNS tumors for whom SmartMatch drug screen analysis results are generated within 21 days from the time of tumor tissue acquisition

Eligibility:

• Participants >=15 years with advanced CNS tumors.
• Participants must have been scheduled for a brain tumor biopsy or resection planned to take place at NIH.

Design:

• Tumor and blood samples will be collected for multi-omic analysis.
• Fresh tumor samples will be used for drug screen analysis by SmartMatch.
• After initial sample collection, participants will be followed remotely every 6 (+/-3) months for 3 years.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jing Wu, M.D.; Phone Number: (240) 760-6036; Email: jing.wu3@nih.gov
• Study Contact Backup: Name: Christine T McGowan; Phone Number: (240) 858-7330; Email: christine.mcgowan@nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: National Cancer Institute Referral Office; Phone Number: 888-624-1937; Email: NCIMO_Referrals@mail.nih.gov

Participation Criteria

Eligibility Criteria

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

Description

• INCLUSION CRITERIA

• Participants must have advanced CNS tumors confirmed by a documented pathology report, including:

  • recurrent isocitrate dehydrogenase (IDH)-wild-type high-grade glioma
  • recurrent IDH-mutant gliomas
  • other recurrent CNS tumors
• Participants must have been scheduled for a brain tumor biopsy or resection. Note: Scheduled brain tumor biopsy or resection must be at least 6 months after any previous radiation therapy, if applicable. All procedures are planned to take place at NIH.
• Age >= 15 years.
• Ability of participant, parent/guardian, or Legally Authorized Representative (LAR) to understand and sign a written informed consent document.

EXCLUSION CRITERIA

None.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 1/SmartMatch testing; Turnaround time for SmartMatch platform implementation and molecular profiling of recurrent CNS tumors	Other: Tumor sample collection; Fresh tumor samples will be collected for the study only if available following a planned biopsy or resection performed at NIH.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the proportion of participants with advanced CNS tumors for whom SmartMatch drug screen analysis results are generated within 21 days from the time of tumor tissue acquisition	Point estimates and 95% exact confidence intervals will be calculated using the Clopper-Pearson method	21 days from the time of tumor tissue acquisition

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To perform molecular profiling of advanced CNS tumors at disease progression.	Descriptive statistics will be used to summarize the molecular profiling results	End of Study

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jing Wu, M.D., National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Aldape K, Brindle KM, Chesler L, Chopra R, Gajjar A, Gilbert MR, Gottardo N, Gutmann DH, Hargrave D, Holland EC, Jones DTW, Joyce JA, Kearns P, Kieran MW, Mellinghoff IK, Merchant M, Pfister SM, Pollard SM, Ramaswamy V, Rich JN, Robinson GW, Rowitch DH, Sampson JH, Taylor MD, Workman P, Gilbertson RJ. Challenges to curing primary brain tumours. Nat Rev Clin Oncol. 2019 Aug;16(8):509-520. doi: 10.1038/s41571-019-0177-5.
• Ostrom QT, Price M, Neff C, Cioffi G, Waite KA, Kruchko C, Barnholtz-Sloan JS. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2015-2019. Neuro Oncol. 2022 Oct 5;24(Suppl 5):v1-v95. doi: 10.1093/neuonc/noac202.
• Nishida-Aoki N, Bondesson AJ, Gujral TS. Measuring Real-time Drug Response in Organotypic Tumor Tissue Slices. J Vis Exp. 2020 May 2;(159). doi: 10.3791/61036.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2026
• Primary Completion (Estimated): December 30, 2030
• Study Completion (Estimated): December 30, 2030

Study Registration Dates

• First Submitted: January 28, 2026
• First Submitted That Met QC Criteria: January 28, 2026
• First Posted (Actual): January 29, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: March 25, 2026

More Information

Terms related to this study

• Keywords: Brain Tumor; Gliomas; Rare Tumor; CNS Tumor; Drug Screen; SmartMatch
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Glioma; Brain Neoplasms; Central Nervous System Neoplasms
• Other Study ID Numbers: 10002539; 002539-C

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated with a ZIA, with a clinical protocol that undergoes scientific review and/or will involve genomic data sharing.
• IPD Sharing Time Frame: Data will be made available as soon as possible or at the time of associated publication. Data not published in a manuscript will be shared via public source once the data set completes QC.
• IPD Sharing Access Criteria: Clinical data will be made available upon request and with the permission of the study PI. Genomic data are made available via dbGAP through requests to the data custodians.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No