UMIN-CTR Clinical Trial

Public title

Bevacizumab treatment of intra-venous administration and diagnostic nuclear medicine for symptomatic radiation necrosis in the brain

Acronym

Bevacizumab treatment for symptomatic radiation necrosis

Scientific Title

Bevacizumab treatment of intra-venous administration and diagnostic nuclear medicine for symptomatic radiation necrosis in the brain

Scientific Title:Acronym

Bevacizumab treatment for symptomatic radiation necrosis

Region

Japan

Condition

Symptomatic radiation necrosis after radiotherapy for primary and metastatic brain tumors, and tumors of the adjacent tissues to the brain

Classification by specialty

Hematology and clinical oncology	Radiology	Neurosurgery

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

This study will evaluate efficacy of bevacizumab treatment of intravenous administration against symptomatic radiation necrosis which is refractory to preexisting medical treatments including corticosteroids, anticoagulants, and vitamin E.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Phase II,III

Primary outcomes

Peri-lesional edema is decreased by more than 30% or equal on MRI after bevacizumab treatment and this reduction has been maintained for 4 weeks.

Key secondary outcomes

Safety of bevacizumab treatment;
The amount of corticosteroids used;
The improvement of patient's performance status after bevacizumab;
The recurrence rate of radiation necrosis within one year from bevacizumab treatment;
The improvement of enhanced area by contrast medium on MRI

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -but assessor(s) are blinded

Control

Historical

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Bevacizumab of 5mg/kg is administered intravenously every other week (day 1, day 15, day 29, day 43, day 57, and day 71), 6 cycles in total. MRI is examined after 3 cycles. Then the rest of 3 cycles are performed if peri-lesional edema is not aggravated.

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

Not applicable

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Radiation necrosis occurring 3 months after radiotherapy for primary and metastatic brain tumors, and tumors of the adjacent tissues to the brain;
Patients with symptomatic radiation necrosis;
A lesion was enhanced by contrast medium accompanying to peri-lesional edema on MRI;
Radiation necrosis is diagnosed with F-BPA-PET or C-MET-PET and tumor recurrence is denied;
With regard to F-BPA-PET, lesion/normal ratios of less than 2.0 and 2.5 were absolute and relative indications for bevacizumab treatment, respectively. With regard to C-MET-PET, L/N ratios of less than 1.25 and 1.8 were absolute and relative indications for bevacizumab treatment, respectively;
Karnofsky performance status more than 60% or equal;
Patients are refractory to medical treatments including corticosteroids, anticoagulants, and vitamin E;
Patients cannot undertake necrotomy because of lesions in the eloquent area or poor general status;
Adequate hematologic, hepatic, and renal function (absolute neutrophil count more than 1500mm3 or equal; platelet count more than 100000mm3 or equal; hemoglobin more than 9.5 g/dl or equal; GOT and GPT less than 2.5 folds; total bilirubin less than 2.0 mg/dl or equal; serum creatinine less than 1.2 mg/dl or equal; urine protein less than 1+ or equal; PT-INR more than 1.5 folds or equal or 1.5 to 2.5 when warfarinization);
Life expectancy greater than 3 months;
Able to provide written informed consent by patients or legally authorized representative;
In cases of radiation necrosis with metastatic brain tumors, no active lesion is systemically detected by PET or other radiographical examinations and values of tumor marker are within normal limit if they are examined.

Key exclusion criteria

Patients are able to undertake necrotomy;
Intracranial tumors are active and recurrent (L/N ratio on F-BPA-PET is greater than 2.5, or L/N ration on C-MET-PET is greater than 1.8;
Patients require intravenous administration of antibiotics, antiviral drugs, and antifugal drugs for infection;
Febrile patients more than 38 degree Celsius of body temperature or equal;
Patients having severe comorbidities such as heart diseases, pulmonary fibrosis, interstitial pneumonia, hemorrhagic diathesis, uncontrollable hypertension or diabetes;
*Comorbidity or history of unstable angina and myocardiac infarction within 6 months
*Uncontrollable peptic ulcer
*Uncontrollable hypertension
*Unhealed advanced wound or fracture
*Comorbidity or history of gastrointestinal perforation and fistula, and abdominal abscess within 6 months
*Comorbidity or history of emoptysis and pulmonary hemorrhage greater than Grade 1
*Comorbidity or history of vascular diseases (venous and arterial thrombosis and embolism, aortic aneurysms) required interventions within 6 months
*Congestive heart failure more than NYHA class I
*Patients with a schedule of an operation during this study or patients having had an operation within 4 weeks;
Patients with hemorrhage (intracranial hemorrhage, gastrointestinal hemorrhage, urinary hemorrhage, hemoptysis);
PT-INR is greater than 2.5 or unstable when warfarinization;
History of severe hypersensitivity or allergy to bevacizumab;
Pregnant patients, patients with a possibility of pregnancy, or patients breastfeeding;
Investigators judge patients who are inappropriate to include this study.

Target sample size

40

Name of lead principal investigator

1st name
Middle name
Last name	Shin-Ichi Miyatake

Organization

Osaka Medical College

Division name

Neurosurgery

Zip code

Address

2-7, Daigakumachi, Takatsuki, Osaka, 569-8686, Japan

TEL

+81-72-683-1221

Email

neu070@poh.osaka-med.ac.jp

Name of contact person

1st name
Middle name
Last name	Shin-Ichi Miyatake

Organization

Osaka Medical College

Division name

Neurosurgery

Zip code

Address

2-7, Daigakumachi, Takatsuki, Osaka, 569-8686, Japan

TEL

+81-72-683-1221

Homepage URL

http://www.osaka-med.ac.jp/deps/neu/

Email

neu070@poh.osaka-med.ac.jp

Institute

Department of Neurosurgery, Osaka Medical College

Institute

Department

Personal name

Organization

Department of Neurosurgery, Osaka Medical College

Organization

Division

Category of Funding Organization

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

京都大学　大学院医学研究科　脳病態生理学講座　脳神経外科（京都府）
社会医療法人厚生会　木沢記念病院　脳神経外科（岐阜県）
筑波大学 放射線腫瘍科　(茨城県）
千葉県がんセンター　脳神経外科　(千葉県）
北海道大学　脳神経外科　(北海道）
都立駒込病院　脳神経外科　(東京都）
熊本大学　脳神経外科　(熊本県）
杏林大学医学部附属病院　脳神経外科　(東京都）
広島大学病院 脳神経外科 (広島県）
久留米大学　脳神経外科　(福岡県）
大分大学医学部附属病院　脳神経外科　(大分県）
国立がん研究センター中央病院　脳脊髄腫瘍科　(東京都）
東京大学医学部附属病院　脳神経外科　(東京都）
岩手医科大学　脳神経外科　(岩手県）
東北大学医学部附属病院　脳神経外科　(宮城県）　

Date of disclosure of the study information

2011

Year

04

Month

07

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

No longer recruiting

Date of protocol fixation

2011

Year

04

Month

01

Day

Date of IRB

Anticipated trial start date

2011

Year

04

Month

01

Day

Last follow-up date

2014

Year

03

Month

01

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2011

Year

04

Month

06

Day

Last modified on

2013

Year

12

Month

25

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000006387