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Open-label study to assess efficacy and safety of a single dose (i.v.) of NMK36 in subjects with high / low- grade glioma.

Open-label study to assess efficacy and safety of a single dose (i.v.) of NMK36 in subjects with high / low- grade glioma.

42

Out of the total number of patients: there were 77.5% (31 out of 40 patients) of males and 22.5% of females (9 out of 40 patients); their age was [mean(standard deviation) and the same hereafter] 55(15.8) years and their body weight was 63.8(10.36) kg.

Forty-two patients were enrolled in this study; 40 of these were included in the safety analysis set, with the exclusion of 2 patients to whom NMK36 was not administered. Five of these 40 patients were excluded from the final analysis set, giving a FAS of 35 patients. Of the 35 patients in the FAS, there was a further exclusion of 2 patients giving a PPS of 33 patients.

Twelve adverse events developed in 7 (17.5%) patients, and 5 adverse reactions developed in 5 (12.5%) of patients out of the 40 patients in the safety analysis group. There were no adverse events which developed in 2 or more patients. With regard to severity, although there was 1 severe adverse event (blood pressure increased), the relationship to NMK36 was judged to be "unrelated", and the event resolved with drug treatment. No serious adverse events were observed and no patients were withdrawn because of the development of adverse events. No clinically significant changes were observed in laboratory test values, vital signs and 12-lead electrocardiograms.

The positive predictive value of 26 regions which could not be delineated by contrast-enhanced T1-weighted imaging but were delineated by NMK36 Scan was 100.0% for the FAS (26 out of 26 regions; 95% confidence intervals, 86.8% to 100.0%, and the lower threshold of 70% was significantly exceeded (p <0.001). There were similar results for the PPS. It is considered that a single-dose intravenous administration of NMK36 may be permitted for clinical use, for patients with clinically suspected high-grade gliomas and low-grade gliomas.

After NMK36 administration, during PET imaging was started from 10 to 20 minutes, the positive predictive value of the regions which could not be delineated by contrast-enhanced T1-weighted imaging but were delineated by NMK36 Scan was 100.0% for both the "high radiation dosage group" and the "low radiation dosage group": NMK36 Scans of the results of assessments of the appraisal regions was 94.1%, and the kappa coefficient was high at 0.824. Of the 23 appraisal regions which failed to be delineated by contrast-enhanced T1-weighted imaging from 40 to 50 minutes after NMK36 administration, but delineated by NMK36 Scan, all had a positive predictive value of the regions assessed histopathologically as tumor of 100.0% (23 out of 23 regions); this was the same result as for the result obtained from10 to 20 minutes after NMK36 administration. Each of the indices SUVmax, T/N (contralateral) ratio, T/N (cerebellar) ratio and %SUVmax of tissue collection sites had high mean values for "tumor" compared with those for "non-tumor".

The results of efficacy assessments showed that NMK36 visualized tumors present in regions of no contrast with MRI, in high-grade glioma patients and low-grade glioma patients. Since the PPV of NMK36 was 100% for both low-grade glioma patients and high-grade glioma patients, this suggests that it is useful for setting the extent of resection of gliomas. It is also considered that the results of safety assessments will enable single-dose intravenous administration of NMK36 to be permitted for clinical use.

Dec. 28, 2016

https://pubmed.ncbi.nlm.nih.gov/28840134/

No

Nihon Medi-Physics Co., Ltd.

3-4-10, Shinsuna, Koto-ku, Tokyo 136-0075, Japan

Nihon Medi-Physics Co., Ltd.

3-4-10, Shinsuna, Koto-ku, Tokyo 136-0075, Japan

+81-3-5634-7363

completed

Oct. 10, 2013

Interventional

non-randomized, open-label, uncontrolled

diagnostic purpose

2

Patients who were clinicaly-suspected with high / low- grade glioma by the clinical sign / course and MRI exam are to have the surgical removal of the tumor.

-Patients who received treatment for glioma.
-Patients who received chemotherapy for malignant tumor within the last 5 years.
-Patients who are pregnant, lactating or possibly pregnant.
-Patients who have hepatic or renal dysfunction.
-Patients with Karnofsky performance status below 40%.

Both

Patients who were clinically- suspected with high / low- grade glioma

investigational material(s)
Generic name etc : fluciclovine(18F)
INN of investigational material : fluciclovine(18F)
Therapeutic category code : 43- Radioactive medicines
Dosage and Administration for Investigational material : The whole contents of 1 vial of NMK36 (2 mL; 185 MBq/2 mL when calibrated) was administered intravenously into, for example, the arm, then flushed with physiological saline. The radiation dosages administered were regulated by the time of administration and were grouped as follows:
(1) High Radiation Dosage Group: Administration in the interval from 1 hour before calibration [270 MBq (-10%~10%)] and calibration [185 MBq (-10%~10%)].
(2) Low Radiation Dosage Group: Administration in the interval from 1 hour after calibration [127 MBq (-10%~10%)] and 2 hours after calibration [87 MBq (-10%~10%)].

control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : -

safety
efficacy
Efficacy: positive-predictive value of PET imaging in the regions which are not visualized by contrast T1-weighted MRI
Safety: subjective/objective symptoms, electrocardiogram exam, vital signs, clinical tests

efficacy
Efficacy: range of administered radioactivity, range of starting time for PET imaging, search for semiquantitative index

Sept. 02, 2013