A Surgical Window of Opportunity Clinical Trial of Troriluzole in Recurrent IDH Wild-Type Glioblastoma

NCT06552260 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 24-339
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 3

Brief Summary

This research study is studying troriluzole as a possible treatment for recurrent glioblastoma. The name of the study drug involved in this research study is:

• Troriluzole (a tripeptide prodrug of riluzole)

Conditions

Glioblastoma; Recurrent Glioblastoma; Brain Tumor

Keywords

Glioblastoma; Recurrent Glioblastoma; Brain Tumor; Isocitrate dehydrogenase wild-type Glioblastoma

Outcome Measures

Primary Outcomes (1)

• The effect of troriluzole on high-gamma band power (a measure of neuronal activity) via electrocorticography during surgical resection

  Data will be summarized using descriptive statistics to compare between participants who received presurgical troriluzole and who did not

  At time of surgery

Secondary Outcomes (6)

• Concentrations of Extracellular Glutamate in Resected Tissue by MALDI-MSI

  From tumor tissue resected at surgery

• Grade 3-5 Treatment Related Adverse Event

  From tumor tissue resected at surgery

• Proliferation Rate (Ki-67) in Resected Tissue

  From tumor tissue resected at surgery

• Protein Levels of NLGN3 in Resected Tissue

  From tumor tissue resected at surgery

• Protein Levels of Phosphorylated AMPA Receptor Subunits (e.g. GluA2) in Resected Tissue

  From tumor tissue resected at surgery

Study Arms (2)

Group A: Presurgical Troriluzole

EXPERIMENTAL

18 participants will be randomly assigned to this group and with complete: * Baseline visit with assessments and MRI. * Cycle 0: * Day -6 through Day 0: Predetermined dose of Troriluzole 2x daily. * Day 0: pre-op MRI * Day 0: standard of care surgical resection of tumor * Day 0: post-op MRI * Cycle 1 through Cycle 3: --Days 1 through 28 of 28 day cycle: Predetermined dose of Troriluzole 2x daily. * Cycle 3 through End of Treatment: --Days 1 through 28 of 28 day cycle: Predetermined dose of Troriluzole 2x daily. * MRIs every 8 weeks while on treatment. * End of study visit with MRI * Follow up every 3 months for 1 year, and then every 6 months for the next 3 years.

Drug: Troriluzole

Group B: Surgery + Troriluzole

EXPERIMENTAL

9 participants will be randomly assigned to this group and with complete: * Baseline visit with assessments and MRI * Day 0: pre-op MRI * Day 0: standard of care surgical resection of tumor * Day 0: post-op MRI * Cycle 1 through Cycle 3: --Days 1 through 28 of 28 day cycle: Predetermined dose of Troriluzole 2x daily. * Cycle 3 through End of Treatment: --Days 1 through 28 of 28 day cycle: Predetermined dose of Troriluzole 2x daily. * MRIs every 8 weeks while on treatment. * End of study visit with MRI * Follow up every 3 months for 1 year, and then every 6 months for the next 3 years.

Drug: Troriluzole

Interventions

Troriluzole DRUG

Tripeptide prodrug of Riluzole, 100 mg capsule, taken orally per protocol.

Also known as: Trigriluzole, BHV-4157, FC-4157, 2-Amino-N-({methyl-[(6-trifluoromethoxy-benzothiazol-2-ylcarbamoyl)-methyl]-carbamoyl}-methyl)-acetamide monohydrate monohydrochloride, C15H16F3N5O4S.HCl.H2O

Group A: Presurgical Troriluzole; Group B: Surgery + Troriluzole

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Histopathologically confirmed IDH-wildtype glioblastoma, WHO Grade 4, and variants including gliosarcoma as per WHO 2021 criteria (38).
• Prior treatment with radiotherapy with or without chemotherapy.
• Recurrent or progressive disease with no more than 2 prior relapses.
• Confirmed measurable disease per RANO 2.0 for GBM.
• Tumor is documented as IDH1/2 wildtype by direct DNA sequencing, provided that it is performed in a CLIA/CAP-certified laboratory.
• Availability of archival formalin fixed paraffin-embedded (FFPE) tumor tissue block or 20 unstained FFPE slides (5 μm thick) from any prior surgery for mutation testing and additional sequencing.
• Karnofsky Performance Status of ≥ 60.
• Candidate for surgical resection.
• Tumor tissue extending to cortical gray matter based on MRI.
• Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.
• Women of child-bearing potential (WOCBP), defined as any individual assigned female at birth physiologically capable of becoming pregnant, must use highly effective contraception during study treatment and for 1 month after study discontinuation. Highly effective contraception is defined as either:
• True Abstinence: When this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception.
• Sterilization: Surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.

You may not qualify if:

• Laboratory values at the Screening Visit:
• ANC count \< 1,500/mm3; growth-factor support within 7 days for filgrastim or other short acting biosimilars or 21 days for pegfilgrastim or other long acting biosimilars to increase the ANC is not allowed.
• Platelets \<100,000/mm3;
• Hemoglobin \< 9 g/dL;
• Total bilirubin \> 2 × the upper limit of normal (ULN) (unless subject has documented history of Gilbert's Syndrome in which case subject may be enrolled if total bilirubin is less than 5 mg/dL, assuming all other criteria are fulfilled);
• Aspartate aminotransferase (AST \[SGOT\]) \> 1.5 x ULN;
• Alanine aminotransferase (ALT \[SGPT\]) \> 1.5 x ULN;
• Serum creatinine \> 1.5 mg/dL or a calculated creatinine clearance \< 60 mL/min; and
• Positive serum β-hCG test in any individual assigned female at birth and is of childbearing potential (defined as ≤ 50 years of age, or \> 50 years of age with a history of amenorrhea for ≤12 months prior to study entry).
• Has presence of diffuse leptomeningeal disease or extracranial disease.
• Prior treatment with troriluzole or riluzole
• From study treatment initiation, treatment with temozolomide less than 23 days, treatment with CCNU or BCNU less than 42 days, treatment with anti-VEGF therapy such as bevacizumab less than 6 months, or treatment with any cancer-directed systemic therapy less than 4 weeks or 5 half-lives, whichever is shorter. No wash-out period is required from tumor treating fields (TTF).
• Use of any investigational agents within 28 days of baseline or 5 half-lives from study initiation, whichever is shorter.
• Radiotherapy within 12 weeks prior to registration unless new enhancement is outside the radiation field (beyond the high-dose region of 80% isodense line) or evidence of viable tumor on histopathologic sampling.
• Presence of a clinically significant allergy, hypersensitivity, or toxicity of prior therapy, with the exception of alopecia or lymphopenia, that has not resolved to ≤ Grade 1 or pre-treatment baseline, as determined by National Cancer Institute CTCAE v 5.0.

Sponsors & Collaborators

• Ugonma Chukwueke: lead
• National Institutes of Health (NIH): collaborator
• Biohaven Pharmaceuticals, Inc.: collaborator

Study Sites (3)

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02215, United States

RECRUITING

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Ugonma Chukwueke, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ugonma Chukwueke, MD

CONTACT

617-632-2166; Ugonma_Chukwueke@DFCI.HARVARD.EDU

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: August 9, 2024
• First Posted: August 13, 2024
• Study Start: February 19, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027
• Last Updated: September 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (3)