A Phase I/IIa Study of Cerebraca Wafer Plus Adjuvant Temozolomide (TMZ) in Patients With Recurrent High Grade Glioma

NCT03234595 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: EFBPOLZ20141120
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 3

Brief Summary

Cerebraca Wafer (75 mg \[(Z)-n-butylidenephthalide\]) is designed for surgical combination to treat glioblastoma (GBM) diseases. High-grade glioma includes GBM (Grade IV, isocitrate dehydrogenase 1 \[IDH1\] wild-type) and anaplastic astrocytoma (Grade IV and Grade III, IDH1 mutation). Among these, GBM is the most common and aggressive brain tumor. Patient suffering from GBM usually develops symptoms such as headaches, seizures, memory loss, and changes in behavior in its early phase. At later stages, patients may encounter loss of movement and sensation, language dysfunction, and cognitive impairments depending on location and size of the tumor. The average survival of recurrent GBM patients is 6 to 9 months regardless of the use of current available therapies. The clinical trial aimed to evaluate the safety and efficacy profiles of Cerebraca Wafer plus adjuvant TMZ in patients with recurrent GBM. Additionally, the study sought to determine the maximum tolerated dose (MTD) of Cerebraca Wafers. This study specifically examined the safety of the intended dose of 6 wafers.

Conditions

Recurrent GBM

Keywords

Cerebraca Wafer; Recurrent high-grade glioma; Astrocytoma; Glioblastoma; IDH wild type; MGMT unmethylation (chemoresistance)

Outcome Measures

Primary Outcomes (2)

• To determine the maximum tolerated dose (MTD) of Cerebraca Wafer by dose limiting toxicity (DLT) in patients with recurrent high-grade glioma.

  MTD and DLT

  2 year

• To evaluate the efficacy profiles of Cerebraca Wafer in patients with recurrent high-grade glioma.

  Overall survival (OS)

  2 year

Study Arms (1)

single arm

EXPERIMENTAL

There is 1 treatment arm with 4 dose cohorts in Phase I and 1 treatment arm in Phase IIa.

Drug: Cerebraca wafer

Interventions

Cerebraca wafer DRUG

Eligible patients will receive Cerebraca wafer implantation with adjuvant temozolomide (TMZ) for the safety and efficacy in this study. At Phase I, the MTD will be determined by DLT. At Phase IIa, up to 12 evaluable patients will be enrolled for the efficacy and safety of Cerebraca wafer implantation. At Phase IIa, the cavity surface after tumor removal will be maximally covered by Cerebraca wafer without exceeding the MTD defined at Phase I. Patients in Phase I receive treatment as designed for Phase IIa, the data will be incorporated into Phase IIa to reduce the patient number. The overall patient number in this study is therefore between 2 to 36 evaluable patients.

single arm

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female or male, age ≥ 20 years old
• Patient has diagnosed recurrent high grade glioma, including anaplastic astrocytoma and glioblastoma multiforme
• Patients have enough cavity after glioma resection for planned number of wafer implantation (by Investigator's judgment)
• Patients have unilateral single focus of tumor in cerebrum
• Patients have the 1st time recurrence of glioma
• Patients undergone standard therapy for their prior glioma episode; for patients with anaplastic astrocytoma, the prior standard therapy should include surgical resection, radiation and adjuvant temozolomide (or PCV \[procarzine, lomustine and vincristine\]; for patients with glioblastoma multiforme the prior standard therapy should include surgical resection, radiation and adjuvant temozolomide
• Patients with Karnofsky Performance Score (KPS) ≥ 50
• Patients are recovered from toxicities from prior systemic therapies and have adequate hematopoietic function at screening and before using study medication
• Absolute neutrophil count (ANC) ≥ 1,000 cells /mm3
• Platelets ≥ 100,000 /mm3
• Total white blood cell (WBC) ≥ 2,500 cells /mm3
• Total bilirubin ≤ 2.5 mg/dL
• AST ≤ 4 x ULN
• ALT ≤ 4 x ULN
• ALP ≤ 5 x ULN

You may not qualify if:

• Phase I and IIa
• Patient who has participated in other investigational studies within 4 weeks prior to receive Cerebraca wafer
• Patient with known or suspected hypersensitivity to Cerebraca wafer, TMZ or the excipient
• Patient has tumor that cannot be surgically removed without significantly affecting vital function
• Patient's glioma locates in the area that is not suitable for Cerebraca wafer implantation
• Patient has external-beam radiation therapy within 4 weeks before study entry
• Patient has other severe and/or life-threatening disease(s) with life expectancy less than 12 months
• Patient has immuno-compromised condition, or is with known autoimmune conditions or is human immunodeficiency virus (HIV) seropositive.
• Patient with medical, social or psychological factors interfering with compliance of the study
• Patient has on-going moderate to severe organ impairment other than study indication that may confound the efficacy evaluation, safety evaluation or usage of TMZ
• At Phase I, patient is planning to use strong cytochrome P450 modulator.
• Female patients are lactating, pregnant, or planned to be pregnant

Sponsors & Collaborators

• Everfront Biotech Co., Ltd.: lead
• DOIT, Ministry of Economic Affairs, Taiwan: collaborator

Study Sites (3)

Hualien Tzu Chi Hospital

Hualien City, Taiwan

Location

Taichung Veterans General Hospital

Taichung, Taiwan

Location

Tri-Service General Hospital

Taipei, Taiwan

Location

MeSH Terms

Conditions

Glioblastoma; Glioma; Astrocytoma

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2017
• First Posted: July 31, 2017
• Study Start: November 1, 2017
• Primary Completion: April 30, 2023
• Study Completion: September 3, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

TW (3)