Study of NPC-07 for Fluorescence-guided Resection of Malignant Gliomas

• Quality of fluorescent tissue [ Time Frame: 1 day ] [ Designated as safety issue: No ]
  Quality of fluorescent tissue by the judgement of the investigator
• Positive predictive value of tissue fluorescence in each biopsy tissue sample [ Time Frame: 1 day ] [ Designated as safety issue: No ]
  Positive predictive value of tissue fluorescence at the biopsy level defined as the number of tumor positive biopsies among all biopsies taken from areas of strong and weak fluorescence.
• Percentage of patients without residual tumor [ Time Frame: 3 days ] [ Designated as safety issue: No ]
  Percentage of patients without residual tumor in the MRI within 72 hours after surgery
• Positive predictive value of non-fluorescent tissue at the biopsy level [ Time Frame: 1 day ] [ Designated as safety issue: No ]
  Positive predictive value of tissue fluorescence at the biopsy level defined as the number of tumor positive biopsies among the non-fluorescent tissue adjacent to fluorescent tissue areas and the tumor distant cortex with respect to tumor (if available).
• Sensitivity as percentage of actual positives and specificity as percentage of actual negatives of fluorescence detection at the biopsy level (if available). [ Time Frame: 1 day ] [ Designated as safety issue: No ]
  Sensitivity as percentage of actual positives(True positive fraction/True positive fraction + False negative fraction)and specificity as percentage of actual negatives of fluorescence detection (True negative fraction/False positive fraction + True negative fraction) at the biopsy level (if available).
• Safety [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  AEs during study period (Day 0 to Day 28), laboratory parameter, vital signs, EKG, pO2
• Pharmacokinetic parameters of NPC-07 and active metabolite (Cmax, AUCt, tmax, t1/2） [ Time Frame: 2 days ] [ Designated as safety issue: No ]
  Pharmacokinetic parameters of 5-ALA and PPVX (Cmax, AUCt, tmax, t1/2）

The aim of the present Phase III study is to assess the positive predictive value of NPC-07 (5-aminolevulinic acid hydrochloride) induced tissue fluorescence, safety and pharmacokinetics following a single dose of NPC-07 orally, at a dose of 20mg/kg/body weight, 3 hours prior to induction of anaesthesia for surgery of patients with newly or recurrent malignant glioma (WHO grades III/IV).

Positive predictive value will be confirmed by percentage of patients showing positive tumor cell identification in all biopsies taken from areas of strong and weak fluorescence. This study will be divided into two stages. After reviewing of the result of safety and pharmacokinetics of NPC-07 in small number of subjects by independent safety monitoring committee, more subjects will receive NPC-07 in Step II.

Inclusion Criteria:

• Aged between 18 and 70 years.
• Radiological suspicion of newly- or recurrent malignant glioma (WHO grades III/IV).
• Indication for surgical tumor resection.
• Karnofsky Performance Score of 60 or higher.
• Provides signed informed consent prior to any study procedures.
• Comply with visit schedule and other rules for patients in study protocol.

Exclusion Criteria:

• Porphyria, hypersensitivity to porphyrins.
• Renal insufficiency: Creatinine 2.0 mg/dL or higher
• Hepatic insufficiency: ALT 100 IU/L or higher, AST 100 IU/L or higher, γ-GTP 100 IU/L or higher or total bilirubin 3 mg/dL or higher
• Chemotherapy or other treatment for other malignant tumors
• Females who are pregnant or potentially childbearing or are breastfeeding
• Participation in other clinical trial in the previous 1 month
• Ineligible patient based on the judgement of the investigator.