UMIN-CTR Clinical Trial

Public title

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

Acronym

Ava-boron for poor prognosis MG

Scientific Title

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

Scientific Title:Acronym

Ava-boron for poor prognosis MG

Region

Japan

Condition

Recurrent malignant glioma

Classification by specialty

Radiology

Neurosurgery

Classification by malignancy

Malignancy

Genomic information

NO

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

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).

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

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

Name of lead principal investigator

1st name
Middle name
Last name	Shin-Ichi Miyatake

Organization

Osaka Medical College

Division name

Department of Neurosurgery

Zip code

Address

Daigakumachi, 2-7, Takatsuki, Osaka, Japan

TEL

072-683-1221

Email

neu070@osaka-med.ac.jp

Name of contact person

1st name
Middle name
Last name	Shin-Ichi Miyatake

Organization

Osaka Medical College

Division name

Department of Neurosurgery

Zip code

Address

Daigakumachi, 2-7, Takatsuki, Osaka, Japan

TEL

072-683-1221

Homepage URL

Email

neu070@osaka-med.ac.jp

Institute

Osaka Medical College

Institute

Department

Personal name

Organization

MEXT

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Japan

Co-sponsor

Translational Research Informatics Center, Foundation for Biomedical Research and Innovation

Name of secondary funder(s)

Organization

Address

Tel

Email

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

大阪医科大学（大阪府）

Date of disclosure of the study information

2017

Year

10

Month

10

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Open public recruiting

Date of protocol fixation

2017

Year

09

Month

19

Day

Date of IRB

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

Other related information

Registered date

2017

Year

09

Month

14

Day

Last modified on

2017

Year

09

Month

14

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000033313