Comparison of Cerebraca Wafer Plus Temozolomide Versus Temozolomide Alone in Recurrent Glioblastoma (Cerebraca-02/3)

A Randomized Trial to Assess the Efficacy and Safety of Cerebraca Wafer Plus Temozolomide Versus Temozolomide Alone in Recurrent Glioblastoma

This study is designed as a multi-center, randomized, open-label trial to evaluate the efficacy of Cerebraca Wafer in patients with recurrent glioblastoma. Cerebraca Wafer is intended for use in recurrent glioblastoma as an adjunct to surgery (followed by standard-of-care temozolomide), demonstrating potential to improve outcomes in this serious and life-threatening condition

Study Overview

• Status: Not yet recruiting
• Conditions: Recurrent Glioblastoma, IDH-Wildtype
• Intervention / Treatment: Drug: Cerebraca wafer; Drug: Temozolomide (for relapsed malignant glioma)

• Study Type: Interventional
• Enrollment (Estimated): 175
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Jui Hao Lee, PhD; Phone Number: +886 2 2756-3796; Email: juihaolee@efbiotech.com
• Study Contact Backup: Name: Jen Wei Liu, PhD; Phone Number: +886 2 2756-3796; Email: davidliu@efbiotech.com

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Legorreta Cancer Center Warren Alpert Medical School of Brown University
      • Contact: Clark C. Chen, MD PhD FAANS; Email: clark_chen@brown.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria, subjects must meet all following criteria for study enrollment:

1. Subject must be aged ≥ 18, regardless of gender

2. Subject must have histologically confirmed glioblastoma with:

   1. Completed first-line therapy including surgery plus temozolomide and radiation (concurrent temozolomide/radiation)
   2. Current presentation being first or second recurrence only
3. Subject must have measurable disease preoperatively with at least one contrast-enhancing MRI-identified lesion measuring ≥ 1 cm in two perpendicular dimensions per RANO 2.0 criteria
4. Subject must be deemed eligible for gross total resection of contrast-enhancing MRI-identified lesion by neurosurgeon's pre-operative assessment, according to RANO II
5. Subject must have Karnofsky Performance Status (KPS) ≥ 70

6. Subject must have recovered from prior therapy toxicities with adequate organ function:

   1. Hemoglobin ≥ 8 g/dL
   2. Platelets ≥ 100,000/mm3
   3. White blood cell count (WBC) ≥ 3,000 cells/mm3
   4. Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
   5. Absolute lymphocyte count (ALC) ≥ 1,000 cells/mm3
   6. Coagulation tests (prothrombin time [PT], activated partial thromboplastin time [APTT], International Normalized Ratio [INR]) ≤ 1.5 × ULN
   7. Total bilirubin (TBIL) < 3 × ULN
   8. Alkaline phosphatase (ALP) ≤ 3 × ULN and/or Gamma glutamyltransferase (GGT) ≤ 1.5 × ULN
   9. Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and/or Alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≤ 3 x ULN
   10. eGFR ≥ 30 mL/min (MDRD formula)
   11. QTc interval: msec ≤ 450 (males) or 470 (females) (Fridericia's formula: QTc=QT/RR(1/3); RR=RR interval)

Exclusion Criteria, subjects with any of the following will be excluded:

1. Histological confirmation of oligodendroglioma or mixed glioma
2. Presence of IDH or H3K27M mutation, or 1p19q co-deletion

3. MRI-identified lesion meeting any criteria:

   1. Multi-focal (defined as 2 non-contiguous contrast enhancement areas > 1 cm in 2 planes on fluid-attenuated inversion recovery, FLAIR or T2-weighted sequences)
   2. Presence of diffuse subependymal or leptomeningeal dissemination
   3. Contrast-enhancing lesion > 6 cm in any dimension
4. Tumor location unsuitable for surgical resection and Cerebraca Wafer implantation in the brain areas where surgical intervention would cause significant neurological deficits
5. Prior bevacizumab treatment with uncontrollable tumor progression
6. History of other malignancy within past 5 years

7. Immunocompromised status or autoimmune conditions requiring systemic immunosuppressive therapy, with the following exceptions:

   1. Patients with autoimmune conditions may be eligible after individual assessment of the condition, its severity, and potential interaction with the Cerebraca Wafer.
   2. Patients with HIV infection are eligible if they:

   i. Have CD4+ T-cell counts ≥350 cells/μL ii. Are on stable anti-retroviral therapy iii. Have HIV viral load below the limit of quantification c. Patients with HBV infection are eligible if they: i. Are on appropriate suppressive anti-viral therapy prior to study enrollment ii. Have no evidence of hepatic decompensation d. Patients with history of HCV infection are eligible if they: i. Have completed curative anti-viral treatment with HCV viral load below the limit of quantification

8. Active, uncontrolled infection or medical condition that could compromise safety and efficacy assessment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group (Cerebraca Wafer); Patients will receive surgical tumor resection, implantation of 6 Cerebraca Wafer (75 mg each, total dose of 450 mg (Z)-BP) at the time of surgery, followed by SOC TMZ therapy.	Drug: Cerebraca wafer; Cerebraca Wafer, (75 mg (Z)-n-butylidenephthalide, (Z)-BP, Implant); Drug: Temozolomide (for relapsed malignant glioma); TMZ as the standard-of-care (SOC) treatment for recurrent glioblastoma.
Active Comparator: Comparative Group (Standard-of-Care); Patients will receive surgical tumor resection, followed by SOC TMZ therapy.	Drug: Temozolomide (for relapsed malignant glioma); TMZ as the standard-of-care (SOC) treatment for recurrent glioblastoma.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median overall survival (OS)	Median overall survival (OS) in recurrent glioblastoma patients (event-based)	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability and Safety Profile	Number of participants with treatment-related adverse events and serious adverse events as assessed by CTCAE v5.0"	24 months
Survival rate	To evaluate survival rate post resection.	6, 9, 12, 18, and 24 months
Median progression-free survival (PFS)	To determine the median progression-free survival (PFS) in recurrent glioblastoma patients.	24 months
PFS rate	To evaluate PFS rate at 6, 9, and 12 months post resection	6, 9, and 12 months

Collaborators and Investigators

• Sponsor: Everfront Biotech Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: January 15, 2026
• First Submitted That Met QC Criteria: January 15, 2026
• First Posted (Actual): January 20, 2026

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: January 15, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Dacarbazine; Triazenes; Imidazoles; Temozolomide
• Other Study ID Numbers: EFBPOLZ-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

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