UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Phase II clinical trial on clinical efficacy and safety of combination therapy of boron neutron capture therapy and bevacizumab for recurrent glioma with poor prognosis
Title of the study (Brief title)	Ava-boron for poor prognosis MG
Region	Japan

Condition
Condition	Recurrent malignant glioma
Classification by specialty	Radiology Neurosurgery
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	1. Clinical effect of combination therapy of boron neutron capture therapy (BNCT) and bevacizumab (BV) using nuclear reactor for patients with recurrent glioma with poor prognosis was compared with overall survival (OS) as indicator. 2. Study the clinical effectiveness and safety of combination therapy of BNCT and BV with progression free survival (PFS) according to RANO (the Response Assessment in Neuro Oncology) and the occurrence of adverse events as indicators.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Explanatory
Developmental phase	Phase II

Assessment
Primary outcomes	Overall survival OS: It is defined as the period from the treatment start date to the death date due to any cause. In surviving cases, we will terminate halfway with the date of final survival confirmation. In the case of non-follow-up cases, we aborted by the last day that survival was confirmed before becoming impossible to pursue.
Key secondary outcomes	PFS by RANO standard: It is defined as the period from the treatment start date to the day when the progression of disease (PD) based on the RANO standard, or until the death date due to any cause. In cases that did not deteriorate, we abort halfway with the final progression-free evacuation date (the date of making a decision other than deterioration). In the case of non-follow-up cases, we abort halfway with the final progression-free confirmation date before becoming impossible to pursue. Expression of adverse events: Evaluate adverse events and serious adverse events that occurred during treatment or within 30 days after the end of treatment. Observed adverse events are evaluated based on Common Toxicity Criteria for Adverse Events v4.0 (CTCAE v4.0).

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Maneuver
Interventions/Control_1	Protocol treatments consist of BNCT, additional and chemotherapy with bevacizumab. Prescription dose by BNCT is regulated as not to be more than 13 Gy-Eq for normal brain. Additional bevacizumab is given biweekly with 10 mg/kg as long as progressive disease judged by RANO criteria. Here: RPA class 3 is non-GBM as initial histology and poor KPS less than 70%. RPA class 7 is GBM as initial histology, age more than 50 and steroids required to maintain ADL. Subgroup of RPA class 7 is GBM as initial histology, age more than 50 and the effect was not seen using BV as an antitumor agent. The MST of these classes is reported as 4.4 months after the recurrence.
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	15 years-old <=
Age-upper limit	85 years-old >
Gender	Male and Female
Key inclusion criteria	1. Patients who are histopathologically diagnosed with glioma 2. Patients who have relapsed after standard treatment (including BV) 3. Patients with recurrent gliomas that have a poor prognosis that falls under any of the following - It is not GBM in the initial histopathological examination, KPS at recurrence is 60% to 70% (RPA class 3)] - It is GBM in the initial histopathological examination, the age at recurrence was over 50 years old and used steroid (RPA class 7) - It is GBM in the initial histopathological examination, the age at recurrence was over 50 years old, and the effect was not seen using BV as an antitumor agent (subgroup of RPA class 7) 4. Patients who have confirmed the following in MRI images taken within 28 days prior to BNCT therapy - Case where the tumor is confined to the one side hemisphere on the supratentorial area, the deepest part is within 60 mm from the scalp (Even if the deepest part is 60 mm or more, cases that are judged to be irradiable by air substitution to the tumor excision cavity are indicated as adaptation). - It is single-shot and does not allow seeding. 5. Patients who aged 15 years or older and under 85 years of age at the time of acquiring consent. 6. Patients with KPS of 60% or more 7. Patients who are expected to survive more than 3 months at the time of acquiring consent 8. Patients with bone marrow, liver, kidney function satisfying the following conditions within 28 days before enrollment - Leukocyte count 3,000 /microlitter or more, Neutrophil count 1,500 /microlitter or more, Hemoglobin 8.0 g/dL or more, Platelet count 100,000 /microlitter or more, AST 100 IU/L or less, ALT 100 IU/L or less, Total bilirubin 1.5 mg/dL or less, Serum creatinine 1.2 mg/dL or less, Urine protein 1+ or less, PT-INR 1.6 or less 9. Patient's consent to participate in this study was obtained in writing from the patient himself
Key exclusion criteria	1. Patients suspected of cerebral radiation necrosis at enrollment 2. Patients with infections requiring intravenous administration such as antibiotics, antivirals, antifungal drugs 3. Patients with fever (over 38C) 4. Patients with serious complications / previous medical history - Unstable angina pectoris, myocardial infarction complications, past within 6 months - Digestive ulcer with poor control - Poor control hypertension, diabetes - Advanced wounds that are not approved for healing, traumatic fractures - Digestive tract perforation, fistula, abdominal abscess complications, past within 6 months - Complication of CTCAE Grade 2 or higher pulmonary hemorrhage (hemoptysis [excretion of occult blood over 2.5 ml]), past history - Complication of vascular disorders (venous / arterial thrombus, embolism, aortic aneurysm) requiring treatment, past within 6 months - Complication of congestive heart failure of II degree or more in NYHA - Pulmonary fibrosis / interstitial pneumonia requiring treatment (CTCAE Grade 2 or higher) - Patients scheduled for surgery during the study or patients under 4 weeks from surgical therapy 5. Patients with phenylketonuria 6. Current bleeding (intracranial hemorrhage, gastrointestinal bleeding, urinary tract hemorrhage, retroperitoneal hemorrhage, hemoptysis, etc.) 7. Under anticoagulant medication, control is unstable or PT-INR is more than 2.5 8. Severe hypersensitivity to components of BPA and BV 9. Pregnant woman or lactating woman 10. Patients who do not agree to contraception participating in this study 11. Patients who participated in other clinical trials within one month prior to acquiring consent 12. Patients who are judged to be inappropriate for participation in this study by an investigator or a test sharing physician for other reasons
Target sample size	20

Research contact person
Name of lead principal investigator	Shin-Ichi Miyatake
Organization	Osaka Medical College
Division name	Department of Neurosurgery
Address	Daigakumachi, 2-7, Takatsuki, Osaka, Japan
TEL	072-683-1221
Email	neu070@osaka-med.ac.jp

Public contact
Name of contact person	Shin-Ichi Miyatake
Organization	Osaka Medical College
Division name	Department of Neurosurgery
Address	Daigakumachi, 2-7, Takatsuki, Osaka, Japan
TEL	072-683-1221
Homepage URL
Email	neu070@osaka-med.ac.jp

Sponsor
Institute	Osaka Medical College
Institute
Department

Funding Source
Organization	MEXT
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor	Translational Research Informatics Center, Foundation for Biomedical Research and Innovation
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	YES
Study ID_1	TRIBRAIN1705
Org. issuing International ID_1	Translational Research Informatics Center, Foundation for Biomedical Research and Innovation
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	大阪医科大学（大阪府）

Other administrative information
Date of disclosure of the study information	2017 Year 10 Month 10 Day

Progress
Recruitment status	Open public recruiting
Date of protocol fixation	2017 Year 09 Month 19 Day
Anticipated trial start date	2017 Year 10 Month 10 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2017 Year 09 Month 14 Day
Last modified on	2017 Year 09 Month 14 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000033313