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Phase 2 clinical trial of boron neutron capture therapy for recurrent high-grade
meningioma using SPM-011 and BNCT30 (BNCT for high-grade meningioma)

Investigator-lead clinical trial of accelerator-based BNCT for high-grade
meninigioma (Accelerator-based BNCT for high-grade meningioma)

18

Seventeen subjects were adopted as PPS. All of them were Asian. Eleven subjects were assigned for experimental arm. Six of them were male and the other 5 were female. Median age was 66.0-year-old (range:56~74). Eight subjects belonged to WHO grade 2 and the other three belonged to WHO grade 3. Regarding KPS, 2 subjects were classified to 100%, 6 were classified to 90%, 3 were classified to 80%. Six subjects were assigned for control arm. One of 6 was male and the other 5 were female. Median age was 65.5-year-old (range:61~71). Four subjects belonged to WHO grade 2 and the other 2 belonged to WHO grade 3. Regarding KPS, 3 subjects were classified to 80%, the other 3 were classified to 90, 70 and 60%, respectively. Median KPS was 90% in treatment arm and 80% in control arm.

No other clinical trial affects to this clinical trial design.

Severe adverse event (SAEs) were not found in control arm. In test treatment arm, SAE occurred in 5 cases (41.7%), 10 events, however no SAE to death was found. In detail, sepsis in 2 cases (16.7%), 2 events and others were agitation, seizure, radiation necrosis, phlegmon, pulmonary embolism, cerebral cyst, wound dehiscence and cerebral hemorrhage. Hospitalization or elongation of hospitalization were the reason of judging SAEs. Phlegmon, pulmonary embolism, and cerebral hemorrhage were the severe adverse events that were not reported in BNCT field at the onset of the event. BNCT (the test drug, neutron generator and combination of them) were not judged as causal relationship to these SAEs.

In this clinical trial, primary endpoint was progression free survival 1 (PFS1) judged by central reviewers, considering pseudoprogression. PFS1 six months, 12 months, 24 months and 36 months of the treatment arm were 100.0%, 60.0%, 25.0% and 12.5%, respectively. On the other hand, PFS1 six months and 12 months of the control arm are 44.4% and 0.0%. There was statistical significance between both arms (P=0.0157). Median PFS1 using Kaplan-Meyer method of treatment arm was 14.4 months (95% CI:7.9,26.4) and that of control arm was 1.4 months (95% CI:1.0,9.0) Hazard ratio using Cox proportional hazard model was 0.19 (95% CI:0.05,0.83)and statistical significant. One of the secondary endpoints PFS3 which was judged by investigators considering pseudoprogression also showed the similar results. While, one of the secondary endpoints was PFS2, judged by central reviewers using the PFS based on first progress disease date. PFS2 6 months, 12 months, 18 months of the treatment arm were 80.8%, 30.3% and 0.0%. PFS2 6 and 12 months of the control arm were 44.4% and 0.0%, respectively. There was no statistical significance between both arms (P=0.1331). Median PFS3 of the test treatment arm and control arm were 7.9 (95% CI:3.4,13.3) and 1.4 (95%CI:1.0,9.0) months, respectively. Hazard ratio was 0.4 (95% CI:0.11,1.42) and was not statistically significant. Three out of 11 subjects in treatment arms were judged as PD based on PFS2 in 32 weeks. While these 3 cases judged as PD based on PFS1 in 96 more than 156 weeks. This seemed to cause big dissociation between PFS1 and PFS2. In PPS, OS 12, 24 and 36 months in treatment arm were 100.0, 90.9 and 63.6%. While OS12 and 24 months in control arm were 100.0 and 0.0%. Median OS were 46.9 (95%CI: 27.1,46.9) months in treatment arm and 18.8 (95%CI: not determined), respectively. Hazard ratio was 0.10 (95%CI:0.01,1.53) and not statistically significant. OS-36 months in the treatment arm was 50.0% for WHO grade 2 and 100% for grade 3 and 63.6% for grade 2 and 3. Median OS was 40.5 (95%CI:17.8,46.9) in grade 2, not determined (95%CI:37.9,NE) in grade 3 and 46.9 (95%CI:27.1,46.9) months, respectively. In the report by Raizer, et al. (J Neurooncol. 117:93-101, 2014), OS 36 months was 43% for grade 2, 38% for grade 3 and 41% for grade 2 and 3. Median OS for grade2, 3, 2 and 3 were 26, 23 and 26 months, respectively. Judging from Raizers data, BNCT test treatment arm showed good OS in every WHO grades.

Accelerator-based BNCT showed good control in recurrent high-grade meningiomas. BNCT arm of PFS1 (primary endpoint) was excellent and statistically significant, compared to control, best-supportive care arm. Median PFS1 in the treatment arm was 14.4 months and hazard ratio was 0.19. Median OS of the treatment arm was 46.9 months. BNCT showed best OS data than the previous best chemotherapy trial (mOS:26 months). Accelerator-based BNCT seemed to be effective for recurrent high-grade meningiomas.

Jan. 21, 2026

Jan. 21, 2026

https://doi.org/10.1093/neuonc/noaf279

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2051190044

Miyatake Shin-ichi

Kansai BNCT Medical Center, Educational Foundation of Osaka Medical and Pharmaceutical University , Osaka Medical and Pharmaceutical University Hospital

2-7 Daigaku-machi, Takatsuki, Osaka

shinichi.miyatake@ompu.ac.jp

Miyatake Shin-ichi

Kansai BNCT Medical Center, Educational Foundation of Osaka Medical and Pharmaceutical University

2-7 Daigakumachi, Takatsuki, Osaka

+81-72-683-1221

shinichi.miyatake@ompu.ac.jp

Complete

Sept. 04, 2019

Interventional

randomized controlled trial

open(masking not used)

no treatment control/standard of care control

parallel assignment

treatment purpose

1.KPS at recurrence is 60 percent or more.
2.Target lesion is intracranially localized by contr ast-enhanced images.
3.Recurrence or progression is confirmed by hea d CT or MRI.
4.Lesions seemed to be unresectable.
5.All target lesions should be treatable using max imum available collimator.
6.Histologically confirmed as high-grade meningioma (WHO grade 2 or 3) at initial diagnosis or at recurrence
7.Previous radiotherapy of target lesion should be equivalent to less than 65Gy by daily 2Gy fractionated X-ray treatment.
8.Previous radiotherapy should be started at leas t 90 days prior to screening.
9.One or more measurable lesions should be confined into neutron irradiation field. If all target or non-target lesions are included in one neutron irradiation field, the case can be included.
10.Patients with bone marrow, liver, kidney function at screening defined as below. Within 14 days just prior to screening, any supportive treatment possibly affect those functions should not be allowed such as G-CSF, blood transfusion and so on.
Kidney function:
Serum creatinine 1.2 mg/dL or less in male and 1.0 mg/dL or less in female
Liver function:
AST less than 5-times institutional upper normal limit
ALT less than 5-times institutional upper normal limit
Bone marrow function:
Hemoglobin 8.0 g/dL or more
Platelet count 80,000 /microlitter or more
Leukocyte count 2,500 /microlitter or more
Neutrophil count 1,500 /microlitter or more
11. Patients without clinically significant abnormalities in ECG
12. Patients without clinically significant abnormalities in Chest X-ray

1.Main target lesions are in infratentorial regions.
2.Patients with other prior or concurrent malignancy within the preceding 5 years, except cured-state carcinoma in situ or skin cancer, are not eligible.
3.Patients who have extra-cranial metastasis
4.Patients who have contrast enhanced lesions out-side of maximum available collimator
5.Patients who have meningeal dissemination
6.Active infection needs to be treated systemically
7.Severe intercurrent medical conditions as follows;
Uncontrolled diabetes mellitus,
Uncontrolled hypertension,
Chronic pulmonary disease such as COPD, interstitial pneumonia, pulmonary fibrosi s, severe pulmonary emphysema,
Renal disease such as chronic renal failure, acute renal failure, nephrotic syndrome,
Heart disease corresponds to grade III or IV in NYHA cardiac function classification,
Other serious complications.
8.Patients with phenylketonuria
9.Patients with hereditary fructose intolerance
10.Patients who have severe allergic reaction to some drugs or contrast-agent including skin eruption, anaphylaxis and serum disease
11.Myocardial infarction, unstable angina, uncontrollable arrhythmia to develop within 6 months prior to scheduled BNCT
12.Patients who were treated with anti-cancer agents within 4 weeks prior to scheduled BNCT
13.Patients who received the surgery for brain tumor extirpation within 30 days prior to scheduled BNCT
14.Patients who were treated with unapproved drug within 4 weeks prior to scheduled BNCT or patients who have currently enrolled or have the willingness to be enrolled to other clinical trial
15.Patients impossible to be used with contrast agent for MRI due to cardiac pacemaker, metal implant, cochlear implant or allergic reaction
16.Female patients desiring pregnancy during observation period of this clinical trial or female patients during pregnancy or breastfeeding. Male or female patients who have the possibility of the pregnancy should keep adequate contraception using birth control pills, condoms, vasectomy, tubal ligation, contraceptive diaphragms, intrauterine devices, spermicidal agents and so on.
17.Patients who are judged as difficult to participate in this trial due to mental disease or psychiatric symptoms, or patients taking major tranquilizer
18.Patients with uncontrolled epilepsy defined as below;
Concurrent frequent hospitalization due to epileptic state and/or clinical symptoms, or treatment need for persistent seizure or symptoms
Necessary for nursing care due to trouble in daily life
19.Patients who were administrated with G-CSF or blood transfusion within 14 days just prior to screening
20.Previous treatment history of BNCT

Both

recurrent high-grade meningioma (WHO grade 2 or 3)

18 candidates matched with inclusion criteria an d not conflicted with exclusion criteria, are divide d into 2 groups by stratified and blocking randomization.
12 cases in trial group are treated with BNCT using SPM-011 and BNCT 30. SPM-011 is administrated 400mg/kg as L-BPA in 2 hours and 100mg/kg as L-BPA in the following one hour. Neutron is irradiated using BNCT 30 to achieve 7.5 Gy-Eq as skin absorbed dose.
6 cases in control group are treated with best supportive care, mainly with cortico-steroids.

high-grade meningioma

Boron Neutron Capture Therapy, BNCT

D008579

D016754

Progression free survival depending on Macdonald assessment judged by central review committee

1) Overall survival
2) Best local control rates during 3 years after treatments depending on Macdonald assessment judged by central review committee and principal and sub investigators of this trial.
3) Progression free survival depending on Macdonald assessment judged by principal and sub investigators of this trial.
4) Response rates during 3 years after treatments judged by central review committee and principal and sub investigators of this trial.
5) Change of KPS

+81-72-683-1221

June. 26, 2019

none