Trial Title:
A Surgical Window of Opportunity Clinical Trial of Troriluzole in Recurrent IDH Wild-Type Glioblastoma
NCT ID:
NCT06552260
Condition:
Glioblastoma
Recurrent Glioblastoma
Brain Tumor
Conditions: Official terms:
Glioblastoma
Brain Neoplasms
Recurrence
Conditions: Keywords:
Glioblastoma
Recurrent Glioblastoma
Brain Tumor
Isocitrate dehydrogenase wild-type Glioblastoma
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Troriluzole
Description:
Tripeptide prodrug of Riluzole, 100 mg capsule, taken orally per protocol.
Arm group label:
Group A: Presurgical Troriluzole
Arm group label:
Group B: Surgery + Troriluzole
Other name:
Trigriluzole
Other name:
BHV-4157
Other name:
FC-4157
Other name:
2-Amino-N-({methyl-[(6-trifluoromethoxy-benzothiazol-2-ylcarbamoyl)-methyl]-carbamoyl}-methyl)-acetamide monohydrate monohydrochloride
Other name:
C15H16F3N5O4S.HCl.H2O
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)
Detailed description:
This is an open-label, randomized window-of-opportunity study of Troriluzole in
participants with surgically accessible, recurrent isocitrate dehydrogenase wild-type
(IDH WT) glioblastoma (GBM). Surgical window-of-opportunity clinical trials test how
active the investigational drug is on tumors. "Investigational" means that the drug is
being studied.
Participants will be randomized using a 2:1 ratio into one of two study treatment groups:
Group A versus Group B. Randomization means a participant is placed into a study group by
chance. Group A will receive Troriluzole prior to and after standard-of-care tumor
resection surgery, while Group B will not receive Troriluzole prior to standard-of-care
tumor resection surgery but will receive Troluzole after surgery.
The research study procedures include screening for eligibility, study treatment visits,
blood tests, tumor biopsies, Magnetic Resonance Imaging (MRI) scans, and
electrocardiograms (ECGs).
It is expected that about 27 participants will take part in this research study
Biohaven Pharmaceuticals is funding this research study by providing study drug.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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.
- Male Partner Sterilization (with the appropriate post-vasectomy documentation
of the absence of sperm in the ejaculate). For female subjects on the study,
the vasectomised male partner should be the sole partner for that participant.
- A barrier method defined as condom or Occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
along with a second contraceptive method as described below:
- Placement of an intrauterine device (IUD) or intrauterine system (IUS)
- Appropriate hormonal contraceptives (including any registered and marketed
contraceptive agent that contains an estrogen and/or a progestational
agent - including oral, subcutaneous, intrauterine
- Male subjects should agree to use a highly effective method of contraception
starting with the first dose of study therapy through 3 months after the last dose
of therapy. Male subjects must not donate semen for 3 months after the last dose of
study treatment.
- Ability to understand and the willingness to sign a written informed consent
document. (Providing consents in as many languages as possible is encouraged)
Exclusion Criteria:
- 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.
- Major surgery within 28 days prior to initiation of study drug.
- Active or clinically unstable bacterial, viral, or fungal infection requiring
systemic therapy.
- Any contraindication to MRI examination.
- Requires medications that are known to be strong inhibitors or inducers of CYP1A2
enzymes or anti-glutamergic agents (e.g., perampanel) or hepatotoxic drugs which may
increase the risk of hepatotoxicity (e.g., allopurinol, methyldopa, sulfasalazine).
A washout of 10 days or 5 half-lives, whichever is shorter, is required prior to
study treatment initiation. Oral contraceptives which contain ethinyl estradiol
(moderate CYP1A2 inhibitor) are allowed.
- Pregnant or lactating female.
- History of interstitial lung disease.
- Known history of hepatitis B, human immunodeficiency virus (HIV), or active
hepatitis C infection requiring treatment with antiviral therapy. NOTE: HIV testing
is not required in the absence of clinical suspicion.
- Any severe, acute, or chronic medical or psychiatric condition, or laboratory
abnormality that may increase the risk associated with study participation or study
drug administration, may interfere with the informed consent process and/or with
compliance with the requirements of the study, or may interfere with the
interpretation of study results and, in the Investigator's opinion, would make the
subject inappropriate for entry into this study.
- Difficulty swallowing or malabsorption syndrome; refractory nausea and vomiting,
chronic gastrointestinal (GI) disease or previous significant bowel resection with
clinically significant sequelae that would preclude adequate absorption of study
drug.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Brigham and Women's Hospital
Address:
City:
Boston
Zip:
02215
Country:
United States
Contact:
Last name:
Eudocia Lee, MD, MPH
Phone:
617-632-2166
Email:
eudocia_lee@dfci.harvard.edu
Investigator:
Last name:
Eudocia Lee, MD, MPH
Email:
Principal Investigator
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Contact:
Last name:
Eudocia Lee, MD, MPH
Phone:
617-632-2166
Email:
eudocia_lee@dfci.harvard.edu
Investigator:
Last name:
Eudocia Lee, MD, MPH
Email:
Principal Investigator
Facility:
Name:
Massachusetts General Hospital Cancer Center
Address:
City:
Boston
Zip:
02215
Country:
United States
Start date:
February 2025
Completion date:
August 1, 2027
Lead sponsor:
Agency:
Eudocia Quant Lee, MD
Agency class:
Other
Collaborator:
Agency:
National Institutes of Health (NIH)
Agency class:
NIH
Collaborator:
Agency:
Biohaven Pharmaceuticals, Inc.
Agency class:
Industry
Source:
Dana-Farber Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06552260
