Study of NPC-07 for Fluorescence-guided Resection of Malignant Gliomas - Full Text View

Purpose

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.

Condition	Intervention	Phase
Malignant Glioma	Drug: NPC-07 for oral administration	Phase 3

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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Aminolevulinic acid Aminolevulinic acid hydrochloride

U.S. FDA Resources

Further study details as provided by Nobelpharma:

Primary Outcome Measures:

Positive predictive value of tissue fluorescence [ Time Frame: 1 day ] [ Designated as safety issue: No ]
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 Outcome Measures:

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）

Enrollment:	45
Study Start Date:	August 2010
Study Completion Date:	December 2011
Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Name: 5-ALA, 5-aminolevulic acid hydrochloride

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01167322

Locations

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

Sponsors and Collaborators

Nobelpharma

Investigators

Study Director:

Soichiro Shibui, MD, PhD

Neurosurgery & Neuro-Oncology Division, National Cancer Center Hospital

More Information

No publications provided

Responsible Party:	Nobelpharma
ClinicalTrials.gov Identifier:	NCT01167322 History of Changes
Other Study ID Numbers:	NPC-07-1
Study First Received:	July 16, 2010
Last Updated:	April 26, 2012
Health Authority:	Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Nobelpharma:

NPC-07, 5-ALA, photodynamic diagnosis, pharmacokinetics

Additional relevant MeSH terms:

Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on May 19, 2013