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

Inclusion Criteria:

1. Female or male, age ≥ 20 years old

2. Patient has diagnosed recurrent high grade glioma, including anaplastic astrocytomaand glioblastoma multiforme

3. Patients have enough cavity after glioma resection for planned number of waferimplantation (by Investigator's judgment)

4. Patients have unilateral single focus of tumor in cerebrum

5. Patients have the 1st time recurrence of glioma

6. Patients undergone standard therapy for their prior glioma episode; for patientswith anaplastic astrocytoma, the prior standard therapy should include surgicalresection, radiation and adjuvant temozolomide (or PCV [procarzine, lomustine andvincristine]; for patients with glioblastoma multiforme the prior standard therapyshould include surgical resection, radiation and adjuvant temozolomide

7. Patients with Karnofsky Performance Score (KPS) ≥ 50

8. Patients are recovered from toxicities from prior systemic therapies and haveadequate 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

• Creatinine ≤ 2.0 mg/dL

• GFR ≥ 30 ml/min/1.73m2

9. Patient with no or mild organ impairment

10. Patients who are eligible and able to participate in the study and accept to enterthe study by signing written informed consent forms

11. Patients agrees not to use food supplementary or dietary that contains Angelicasinensis after Screening Visit to Day 21

12. All male patients and female patients with child-bearing potential (between pubertyand 2 years after menopause) should use appropriate contraception method(s) for atleast 4 weeks after Cerebraca wafer treatment and TMZ treatment (whichever islonger) shown below.

• Total abstinence (when this is in line with the preferred and usual lifestyleof the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal,post-ovulation methods) and withdrawal are not acceptable methods ofcontraception).

• Female sterilization (have had surgical bilateral oophorectomy with or withouthysterectomy) or tubal ligation at least six weeks before taking studytreatment. In case of oophorectomy alone, only when the reproductive status ofthe woman has been confirmed by follow up hormone level assessment.

• Male sterilization (at least 6 months prior to screening). For female subjectson the study, the vasectomized male partner should be the sole partner for thatsubject

• Combination of any two of the following (a+b or a+c, or b+c):

1. Use of oral, injected or implanted hormonal methods of contraception orother forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermalhormone contraception.
2. Placement of an intrauterine device (IUD) or intrauterine system (IUS).
3. Barrier methods of contraception: Condom or Occlusive cap (diaphragm orcervical/vault caps) with spermicidal foam/gel/film/cream/vaginalsuppository.

Phase IIa The inclusion criteria for Phase IIa is the same as in Phase I

Exclusion Criteria:

Phase I and IIa

1. Patient who has participated in other investigational studies within 4 weeks priorto receive Cerebraca wafer

2. Patient with known or suspected hypersensitivity to Cerebraca wafer, TMZ or theexcipient

3. Patient has tumor that cannot be surgically removed without significantly affectingvital function

4. Patient's glioma locates in the area that is not suitable for Cerebraca waferimplantation

5. Patient has external-beam radiation therapy within 4 weeks before study entry

6. Patient has other severe and/or life-threatening disease(s) with life expectancyless than 12 months

7. Patient has immuno-compromised condition, or is with known autoimmune conditions oris human immunodeficiency virus (HIV) seropositive.

8. Patient with medical, social or psychological factors interfering with compliance ofthe study

9. Patient has on-going moderate to severe organ impairment other than study indicationthat may confound the efficacy evaluation, safety evaluation or usage of TMZ

10. At Phase I, patient is planning to use strong cytochrome P450 modulator.

11. Female patients are lactating, pregnant, or planned to be pregnant