A Phase I/IIa Study of Cerebraca Wafer Plus Adjuvant Temozolomide (TMZ) in Patients With Recurrent High Grade Glioma
A Phase I/IIa Study to Determine the Maximum Tolerated Dose (MTD) and to Evaluate the Safety and Efficacy Profile of Cerebraca Wafer Plus Adjuvant Temozolomide (TMZ) in Patients With Recurrent High Grade Glioma.
High grade gliomas, glioblastoma multiforme (grade IV) and anaplastic anaplastic astrocytoma (Grade III), are the most comment malignant brain tumor. The cause of gliomas remains unknown. Despite of several researches on environmental hazards and genetic alterations, no direct causes were found.
Patient suffering from glioma 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 glioblastoma patients is 15 months regardless of the use of multimodal therapy.
(Z)-BP/polymer wafer, designated as Cerebraca wafer, is a biodegradable wafer for interstitial implantation comprises (Z)-n-butylidenephthalide ((Z)-BP; the active moiety) and Carboxyphenoxypropane-Sebacic Acid Copolymer (CPPSA; the excipient).
Cerebraca wafer, the first human-use drug product, is a biodegradable implant comprises (Z)-n-butylidenephthalide ((Z)-BP) and CPPSA. According to pre-clinical study, (Z)-BP could reduce glioma migration and invasion, it also could reduce the tumor stem cell marker gens.
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
|Official Title:||Everfront Biotech Co., Ltd.|
- Determination of the DLT/MTD of Cerebraca Wafer with TMZ (Temozolomide) in patients with recurrent high grade glioma. [ Time Frame: 1 year ]
It is a phase I/IIa study of Cerebraca Wafer, intracerebral implantation after resection of tumor, plus adjuvant Temozolomide (TMZ) in patients with recurrent high grade glioma (Grade III and Grade IV; anaplastic astrocytoma and glioblastoma multiforme).
Phase I: at least 2 patients and up to 24 patients. Phase IIa: 12 patients. The main study will end at 24 weeks after all patients receive Cerebraca Wafer implantation. If confirmation tumor response assessment is needed, additional 4 weeks study duration for Main Study Period is allowed. The clinical data at Main Study Period will be summarized in a Main Study Clinical Study Report (CSR).
All patients will be followed in the Extended Period for the efficacy and safety profiles until any one of study cut-off criteria is met, and a CSR will summarize the clinical data covering the overall study period.
NCI-CTCAE 4.03 will be used for grading of the toxicity of Cerebraca wafer.
- Evaluation of the efficacy/safety profile of Cerebraca Wafer with TMZ (Temozolomide) in patients with recurrent high grade glioma. [ Time Frame: 2 year ]
NCI-CTCAE 4.03 will be used for grading of the toxicity (AE) of Cerebraca wafer.
Tumor response evaluation will be based on Updated Response Assessment Criteria for High-Grade Gliomas: Response Assessment in Neuro-Oncology Working Group (RANO).
|Anticipated Study Start Date:||September 1, 2017|
|Estimated Study Completion Date:||August 31, 2018|
|Estimated Primary Completion Date:||December 31, 2017 (Final data collection date for primary outcome measure)|
Experimental: single arm
There is 1 treatment arm with 4 dose cohorts in Phase I and 1 treatment arm in Phase IIa.
Drug: Cerebraca wafer
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.
There are a main study period and extended period in this study. Main study period Screening Day -30~-1
- informed consent signed/given
- Screening evaluation Day 0~7
(1) Tumor resection and Cerebraca wafer implantation (2)Blood sampling for PK (3) Blood sampling for PD (4) Evaluation Day10~24
- Blood sampling for PK
- Blood sampling for PD
- Evaluation Extended period/Follow-up:Every 56 days (8 weeks) The main study will end at 24 weeks after all patients (including Phase I and IIa) receive Cerebraca implantation. If confirmation tumor response assessment is needed, additional 4 weeks study duration for Main Study Period is allowed.
All patients will be followed in the Extended Period for the efficacy and safety profiles until any one of study cut-off criteria is met.
Study cut-off criteria: (Applies to phase I and IIa) (1)90% patient died or loss of follow-up (2)2 years after the last patient receives Cerebraca wafer implantation
Please refer to this study by its ClinicalTrials.gov identifier: NCT03234595
|Contact: Jui-Hao Lee||(+8863)email@example.com|