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

• NPC-07 for oral administration (Drug), also known as 5-ALA, 5-aminolevulic acid hydrochloride: NPC-07, containing 1.5g of 5-aminolevulinic acid hydrochloride per vial, is dissolved in 50 mL of water and will be administered orally 3 hours (range 2-4 hours) prior to induction of anesthesia at a dose of 20mg/kg body weight.

Primary outcomes

• Positive predictive value of tissue fluorescence [1 day]: Positive predictive value of tissue fluorescence defined as the percentage of patients showing positive tumor cell identification in all 6 biopsies taken from areas of strong and weak fluorescence.

Secondary outcomes

• Quality of fluorescent tissue [1 day]: Quality of fluorescent tissue by the judgement of the investigator
• Positive predictive value of tissue fluorescence in each biopsy tissue sample [1 day]: 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 [3 days]: 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 [1 day]: 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). [1 day]: 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 [28 days]: 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） [2 days]: Pharmacokinetic parameters of 5-ALA and PPVX (Cmax, AUCt, tmax, t1/2）

Sex: All, ages: 18 Years to 70 Years

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.

• Soichiro Shibui, MD, PhD, Study director, Neurosurgery & Neuro-Oncology Division, National Cancer Center Hospital