Comparison of Cerebraca Wafer Plus Temozolomide Versus Temozolomide Alone in Recurrent Glioblastoma

Official title

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

Overview

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

Interventions

• 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.

Primary outcome measures

• Median overall survival (OS) [Time frame: 24 months]

Secondary outcome measures (4)

• Tolerability and Safety Profile [Time frame: 24 months]
• Survival rate [Time frame: 6, 9, 12, 18, and 24 months]
• Median progression-free survival (PFS) [Time frame: 24 months]
• PFS rate [Time frame: 6, 9, and 12 months]

Eligibility criteria

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

• Subject must be aged ≥ 18, regardless of gender
• Subject must have histologically confirmed glioblastoma with:

• Completed first-line therapy including surgery plus temozolomide and radiation (concurrent temozolomide/radiation)
• Current presentation being first or second recurrence only
• 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
• 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
• Subject must have Karnofsky Performance Status (KPS) ≥ 70
• Subject must have recovered from prior therapy toxicities with adequate organ function:

• Hemoglobin ≥ 8 g/dL
• Platelets ≥ 100,000/mm3
• White blood cell count (WBC) ≥ 3,000 cells/mm3
• Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
• Absolute lymphocyte count (ALC) ≥ 1,000 cells/mm3
• Coagulation tests (prothrombin time \[PT\], activated partial thromboplastin time \[APTT\], International Normalized Ratio \[INR\]) ≤ 1.5 × ULN
• Total bilirubin (TBIL) < 3 × ULN
• Alkaline phosphatase (ALP) ≤ 3 × ULN and/or Gamma glutamyltransferase (GGT) ≤ 1.5 × ULN
• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and/or Alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≤ 3 x ULN
• eGFR ≥ 30 mL/min (MDRD formula)
• 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:

• Histological confirmation of oligodendroglioma or mixed glioma
• Presence of IDH or H3K27M mutation, or 1p19q co-deletion
• MRI-identified lesion meeting any criteria:

• 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)
• Presence of diffuse subependymal or leptomeningeal dissemination
• Contrast-enhancing lesion > 6 cm in any dimension
• Tumor location unsuitable for surgical resection and Cerebraca Wafer implantation in the brain areas where surgical intervention would cause significant neurological deficits
• Prior bevacizumab treatment with uncontrollable tumor progression
• History of other malignancy within past 5 years
• Immunocompromised status or autoimmune conditions requiring systemic immunosuppressive therapy, with the following exceptions:

• Patients with autoimmune conditions may be eligible after individual assessment of the condition, its severity, and potential interaction with the Cerebraca Wafer.
• 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

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Legorreta Cancer Center Warren Alpert Medical School of Brown University — Providence

Identifiers

NCT: NCT07349693 · EFBPOLZ-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗