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

Malignant Glioma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01167322
• Other study ID #: NPC-07-1
• Status: Completed
• Phase: Phase 3
• First received: July 16, 2010
• Last updated: April 26, 2012
• Start date: August 2010
• Est. completion date: December 2011

Study information

• Verified date: April 2012
• Source: Nobelpharma
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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, ?-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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Glioma
• Malignant Glioma

Intervention

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.

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	International Medical Center, Saitama Medical University	Hidaka	Saitama
Japan	Kyorin University Hospital	Mitaka	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Nobelpharma

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Quality of fluorescent tissue	Quality of fluorescent tissue by the judgement of the investigator	1 day	No
Secondary	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	No
Secondary	Percentage of patients without residual tumor	Percentage of patients without residual tumor in the MRI within 72 hours after surgery	3 days	No
Secondary	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	No
Secondary	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	No
Secondary	Safety	AEs during study period (Day 0 to Day 28), laboratory parameter, vital signs, EKG, pO2	28 days	Yes
Secondary	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	No