Safety and Efficacy Study of Intracranially Implanted Carmustine to Treat Recurrent Malignant Glioma

• Overall Survival Rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Progress Free Survival Rate at 6 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Tumor response rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• KPS Score [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• QOL Score [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Safety of intracranially implanted carmustine after maximal tumor resection [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  Occurrence rate of adverse event and serious adverse event revealed by laboratory test outcomes including blood routine and chemistry as well as physical examination, vital signs including blood presure, temperature, respiratory rate , heart rate.

The purpose of the study is to determine the safety and efficacy of intracranially implanted Carmustine in the treatment of patients with recurrent malignant glioma.

Malignant gliomas recur mostly 2 cm within originated area. Local therapies therefore become particular important. Gliadel wafer developed in the States and marketed in the developed countries is an example of such treatments. The product in this study, Carmustine Sustained Release Implant (CASANT), is similar to that of Gliadel wafer as for the API(Active Pharmaceutical Ingredient), but different as for drug delivering system. As required, the preliminary clinical studies were conducted in China. Based on the results of phase I/II , 8-10 wafers containing given dose of BCNU will be administered intracranially in this phase III to the tumor resected cavity to investigate the safety and efficacy in the treatment of recurrent malignant glioma in 212 patients.

• Anaplastic Astrocytoma
• Anaplastic Oligodendroglioma
• Anaplastic Oligoastrocytoma
• Glioblastoma

• Drug: Carmustine(BCNU)
  Carmustine Sustained Release Implant
  Other Name: BCNU
• Procedure: Surgery
  Routine tumor resection surgery

• Experimental: Carmustine Sustained Release Implant
  Intervention: Drug: Carmustine(BCNU)
• Sham Comparator: Surgical control group
  Intervention: Procedure: Surgery

Inclusion Criteria:

• Patients must be 18 to 70 years old, signed ICF;
• At least 4 weeks after previous chemotherapy (6 weeks since nitrosoureas);
• KPS ≥ 60;
• Unilateral, Supratentorial, solitary lesion and not crossing the midline(exclude patients with little tumors near the resectable tumor even if investigators think they are single lesions)
• No obvious important organ dysfunction: Blood routine: White blood cell (WBC) ≥ 4.0×109/L, Absolute neutrophil count (ANC)≥ 1.5×109/L, Platelets≥ 100×109/L, Hemoglobin≥ 90 g/L; Hepatic function:Serum total bilirubin ≤1.5 times upper limit of laboratory normal; Aspartate aminotransferase (AST) and/or Alanine aminotransferase (ALT)＜2.5 times upper limit of laboratory normal; Renal function:Serum creatinine ≤1.5 times upper limit of laboratory normal;
• Not Pregnant or lactating for women of childbearing potential.

Exclusion Criteria:

• Tumor located at ventricular system, Open ventricle tumor cavity postoperatively;
• Concomitant with other life-threatening diseases and with life expectancy ＜3 months;
• Allergic to nitrosourea drugs;
• With history of intracranial radiotherapy or implant chemotherapy;
• With serious cardiac, pulmonary, hepatic and renal dysfunction, poor glycemic control;
• Investigators thought unsuitable for enrollment.