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

Prior treatment

• Patient who has participated in other investigational studies within 4 weeks prior to receive Cerebraca wafer
• 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

Other illness

• Patient with known or suspected hypersensitivity to Cerebraca wafer, TMZ or the excipient
• 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 has on-going moderate to severe organ impairment other than study indication that may confound the efficacy evaluation, safety evaluation or usage of TMZ

Other

• Phase I and IIa
• Patient has tumor that cannot be surgically removed without significantly affecting vital function
• Patient with medical, social or psychological factors interfering with compliance of the study
• At Phase I, patient is planning to use strong cytochrome P450 modulator.
• Female patients are lactating, pregnant, or planned to be pregnant

• 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
  • Creatinine ≤ 2.0 mg/dL
  • GFR ≥ 30 ml/min/1.73m2
• Patient with no or mild organ impairment
• Patients who are eligible and able to participate in the study and accept to enter the study by signing written informed consent forms
• Patients agrees not to use food supplementary or dietary that contains Angelica sinensis after Screening Visit to Day 21
• All male patients and female patients with child-bearing potential (between puberty and 2 years after menopause) should use appropriate contraception method(s) for at least 4 weeks after Cerebraca wafer treatment and TMZ treatment (whichever is longer) shown below.
  • Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception).
  • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
  • Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject
  • Combination of any two of the following (a+b or a+c, or b+c):
  • Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate \<1%), for example hormone vaginal ring or transdermal hormone contraception.
  • Placement of an intrauterine device (IUD) or intrauterine system (IUS).
  • Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.
  • Phase IIa The inclusion criteria for Phase IIa is the same as in Phase I