Investigator-lead clinical trial of accelerator-based BNCT for high-grade meninigioma

JRCT ID: jRCT2051190044

Registered date:04/09/2019

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: recurrent high-grade meningioma (WHO grade 2 or 3)
• Date of first enrollment: 04/09/2019
• Target sample size: 18
• Study type: Interventional

Intervention(s)

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.

Outcome(s)

• Primary Outcome: Progression free survival depending on Macdonald assessment judged by central review committee

Secondary Outcome

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

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: < 75age old
• Gender: Both

Include criteria

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

Exclude criteria

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

Related Information

• Primary Sponsor: Miyatake Shin-ichi
• Secondary Sponsor: Ono Koji