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Randomized open multicenter study to assess efficacy (for patient outcome) and safety of a single dose (i.v.) of NMK36 in patients with clinically- suspected glioma

Randomized open multicenter study to assess efficacy (for patient outcome) and safety of a single dose (i.v.) of NMK36 in patients with clinically- suspected glioma

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SAS: In terms of sex, 72.0% were men (18/25 patients), 28.0% were women (7/25 patients) and the mean age [mean (standard deviation)] was 54.3(17.4) years. Co-morbidity was present in 64.0% (16/25 patients) of patients, the KPS score was 90% in 36.0% (9/25 patients), which was the most common, and the majority of patients had scores of 90% or 100%.

Among the 26 enrolled patients in the NMK36 administration group, 25 patients were in the Safety Analysis Set; one patient did not receive NMK36 and was excluded. Among the 25 patients in the Safety Analysis Set, one patient was excluded due to "Tumor resection not performed", and 24 patients were defined as the FAS (patient outcome evaluation). All 24 patients in the FAS (patient outcome evaluation) were defined as the PPS (patient outcome evaluation) and FAS (hospital) populations. All 23 enrolled patients in the control group were defined as the FAS (patient outcome evaluation), and among them, one patient was excluded, and 22 patients were defined as the PPS (patient outcome evaluation). In addition, among the 23 patients in the FAS (patient outcome evaluation), 2 patients were excluded, and 21 patients were defined as the FAS (hospital).

Regarding the adverse events, a mild and non-serious puncture site swelling (PT) was observed once in one patient (4.0%) out of the 25 patients in the Safety Analysis Set in this clinical trial. This event occurred as an incidental event due to NMK36 administration, and recovered with no intervention. No clinically significant changes were detected in laboratory test values, vital signs, or 12-lead ECG.

In terms of efficacy, the %9mo-PFS (direct method) in the suspected high-grade glioma group [FAS (patient outcome evaluation)] was 33.3% in the NMK36 administration group (4/12 patients) and 46.7% in the control group (7/15 patients). In terms of the safety evaluation, the administration of a single intravenous dose of NMK36 (2 mL, 185 MBq at the date and time of verification) to patients with clinically suspected high-grade glioma or low-grade glioma was considered to be acceptable for clinical use.

The %6mo-PFS (direct method) in the suspected high-grade glioma group [FAS (patient outcome evaluation)] was higher in the NMK36 administration group (69.2%, 9/13 patients) than in the control group (60.0%, 9/15 patients). The %9mo-PFS (direct method) in the suspected low-grade glioma group [FAS (patient outcome evaluation)] was higher in the NMK36 administration group than in the control group. The results of a comparison of PFS between the groups using the Kaplan-Meier method showed no statistically significant difference between any of the subset populations. NMK36 images contributed to the enlargement or reduction of the extent of tumor resection in 37.5% (9/24 patients) during tumor resection planning. Enlargement occurred in 46.7% (7/15 patients) and reduction occurred in 6.7% (1/15 patients) in the suspected high-grade glioma group, while enlargement occurred in 0.0% (0/9 patients) and reduction occurred in 11.1% (1/9 patients) in the suspected low-grade glioma group.

The results of the efficacy evaluation showed that the %9mo-PFS in the NMK36 administration group in the suspected high-grade glioma group, which was the primary endpoint, was lower than in the control group and that the predefined criteria for success were not achieved. The primary cause may be due to bias in the poor prognostic factors. In terms of the safety evaluation, the administration of a single intravenous dose of NMK36 was considered to be acceptable for clinical use.

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

Sept. 28, 2015

Interventional

randomized, parall-group comparison, open-label

diagnostic purpose

3

Patients with diagnosed as suspected low/high-grade glioma by the clinical sign/course and MRI exam and scheduled for the surgical resection of the tumor.

-Patients who had received or under treatment of glioma or had received needle biopsy for diagnosis.
-Patients who had 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 50.
-Patients who received or are to receive 11C-MET-PET during trial.

Both

Patients with clinically- suspected 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 : (NMK36 administration group only) The entire contents of a single vial of NMK36 (2 mL, 185 MBq at the time of verification) was administered via a forearm vein, then the line was flushed with physiological saline. Administration time was adjusted so that radiation doses would be between 78.3 MBq and 297.0 MBq.

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

safety
efficacy
Efficacy: comparison of Progression Free Survival rate during 9months in patients with clinically- suspected high-grade glioma between groups
Safety: subjective/objective symptoms, electrocardiogram exam, vital signs, clinical tests

efficacy
Efficacy: comparison of Progression Free Survival rate during 6months, comparison of Progression Free Survival rate during 9months other than suspected high-grade glioma, comparison of Progression-Free Survival periods, the rate that NMK36-PET contributes to decide or changes the area of tumor-resection, positive-predictive value of PET imaging in the regions which are not visualized clearly by contrast T1-weighted MRI, sensitivity and specificity of NMK36-PET for collected samples, semiquantitative index to detect tumor-extent, inter-reader concordance rate for the reading of NMK36 images, comparison of pathological findings between the regions which NMK36-PET visuallized or not, rate of patients with diagnosed as histopathologically high-grade glioma in patients with suspected low-grade glioma

Aug. 19, 2015