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

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

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.

Study Overview

• Status: Completed
• Conditions: Malignant Glioma
• Intervention / Treatment: Drug: NPC-07 for oral administration

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Saitama
    • Hidaka, Saitama, Japan, 350-1298
      • International Medical Center, Saitama Medical University
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
    • Mitaka, Tokyo, Japan, 181-8611
      • Kyorin University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Nobelpharma
• Investigators: Study Director: Soichiro Shibui, MD, PhD, Neurosurgery & Neuro-Oncology Division, National Cancer Center Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: July 16, 2010
• First Submitted That Met QC Criteria: July 20, 2010
• First Posted (Estimate): July 22, 2010

Study Record Updates

• Last Update Posted (Estimate): April 27, 2012
• Last Update Submitted That Met QC Criteria: April 26, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: NPC-07, 5-ALA, photodynamic diagnosis, pharmacokinetics
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma
• Other Study ID Numbers: NPC-07-1