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

Study Overview
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Brief Summary
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The purpose of the study is to determine the safety and efficacy of intracranially implanted Carmustine in the treatment of patients with primary malignant glioma.

Detailed Description
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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 primary malignant glioma in 236 patients.

Official Title
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Phase 3 Study of Carmustine Sustained Release Implant (CASANT) to Treat Newly Diagnosed Malignant Glioma

Conditions
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Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Anaplastic Oligoastrocytoma, Glioblastoma

Intervention / Treatment
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* Drug: Carmustine
* Procedure: tumor resection surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmation of high grade glioma(WHO III or above)by frozen or squash preparation; 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 No obvious important organ dysfunction: 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: Underwent cytoreductive surgery(excluded stereotactic biopsy); With chemotherapy or brain radiotherapy history; Tumor located at ventricular system, Open ventricle tumor cavity postoperatively; Concomitant with other life-threatening diseases and with life expectancy <12 months; Allergic to nitrosourea drugs; With history of intracranial radiotherapy or implant chemotherapy; With serious cardiac, pulmonary, hepatic and renal dysfunction, poor glycemic control; Experienced > 3 times of Large epilepsy within one month preoperatively. Investigators thought unsuitable for enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Carmustine Sustained Release Implant<br>For subjects in this group, they will accept intracranially implanted carmustine intraoperatively. | Drug: Carmustine<br>* As Experimental group, subjects will accept specified wafers of carmustine in the cavity while gliomas maximally be resected.<br>* Other names: Other name: BCNU;|
| Sham Comparator: Tumor Resection Surgery<br>For subjects in this control group, they accept no implants while gliomas maximally be resected. | Procedure: tumor resection surgery<br>* For this group, subjects will accept routine tumor resection surgery and place no implant wafers.<br>* Other names: blank control group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | 15 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progress Free Survival |  | 15 months | 
| Overall Survival Rate at 12 months |  | 15 months | 
| Karnofsky Performance Status(KPS) |  | 15 months | 
| Quality of Life(QOL) |  | 15 months | 
| Safety of intracranially implanted carmustine after maximal tumor resection | 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 pressure, temperature, respiratory rate , heart rate. | 15 months |