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

Study Overview
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Brief Summary
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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.

Official Title
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Clinical Study to Assess the Positive Predictive Value of NPC-07 Induced Tissue Fluorescence in Patients With Malignant Glioma (WHO Grades III/IV)

Conditions
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Malignant Glioma

Intervention / Treatment
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* Drug: NPC-07 for oral administration


Participation Criteria
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Eligibility Criteria
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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.

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: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NPC-07<br>Single administration of NPC-07 at a dose of 20mg/kg body weight | Drug: NPC-07 for oral administration<br>* 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.<br>* Other names: 5-ALA, 5-aminolevulic acid hydrochloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive predictive value of tissue fluorescence | 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. | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of fluorescent tissue | Quality of fluorescent tissue by the judgement of the investigator | 1 day | 
| Positive predictive value of tissue fluorescence in each biopsy tissue sample | 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. | 1 day | 
| Percentage of patients without residual tumor | Percentage of patients without residual tumor in the MRI within 72 hours after surgery | 3 days | 
| Positive predictive value of non-fluorescent tissue at the biopsy level | 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). | 1 day | 
| Sensitivity as percentage of actual positives and specificity as percentage of actual negatives of fluorescence detection at the biopsy level (if available). | 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). | 1 day | 
| Safety | AEs during study period (Day 0 to Day 28), laboratory parameter, vital signs, EKG, pO2 | 28 days | 
| Pharmacokinetic parameters of NPC-07 and active metabolite (Cmax, AUCt, tmax, t1/2） | Pharmacokinetic parameters of 5-ALA and PPVX (Cmax, AUCt, tmax, t1/2） | 2 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NPC-07, 5-ALA, photodynamic diagnosis, pharmacokinetics