UMIN-CTR Clinical Trial

Public title

A multicenter randomized phase III study for recurrent glioblastoma comparing bevacizumab alone with dose-dense temozolomide followed by bevacizumab (JCOG1308C, RE-GEND-pIII)

Acronym

A multicenter randomized phase III study for recurrent glioblastoma comparing bevacizumab alone with dose-dense temozolomide followed by bevacizumab (JCOG1308C, RE-GEND-pIII)

Scientific Title

A multicenter randomized phase III study for recurrent glioblastoma comparing bevacizumab alone with dose-dense temozolomide followed by bevacizumab (JCOG1308C, RE-GEND-pIII)

Scientific Title:Acronym

A multicenter randomized phase III study for recurrent glioblastoma comparing bevacizumab alone with dose-dense temozolomide followed by bevacizumab (JCOG1308C, RE-GEND-pIII)

Region

Japan

Condition

Glioblastoma at the first relapse or progression

Classification by specialty

Neurosurgery

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

The aim of this Phase III study is to evaluate the superiority of dose-dense temozolomide (ddTMZ) followed by bevacizumab at ddTMZ failure for glioblastoma at first recurrence or progression, comparing to bevacizumab alone.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Developmental phase

Phase III

Primary outcomes

Overall survival

Key secondary outcomes

Progression-free survival (PFS), 6-month PFS (6m-PFS), complete response rate, response rate, adverse events, serious adverse events, PFS from bevacizumab (BEV) initiation, 6m-PFS from BEV initiation, overall survival from BEV initiation

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

NO

Dynamic allocation

YES

Institution consideration

Institution is considered as adjustment factor in dynamic allocation.

Blocking

NO

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Arm A: Bevacizumab alone(10 mg/kg, day 1 div, every 2 weeks)

Interventions/Control_2

Arm B: Dose-dense temozolomide (ddTMZ)-bevacizumab (BEV) sequential combination therapy.
Temozolomide (120 mg/m2, po, 7 days on/7 days off, every 2 weeks per cycle) up to 48 cycles. The dose will be escalated to 150 mg/m2 at 3rd cycle if the defined conditions are met throughout the first 2 cycles.
At recurrence or progression, bevacizumab alone(10 mg/kg, day 1 div, every 2 weeks)

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

20

years-old

<=

Age-upper limit

75

years-old

>=

Gender

Male and Female

Key inclusion criteria

1) Histologically proven diagnosis of glioblastoma (including giant cell glioblastoma and gliosarcoma).
2) For patients who did not undergo surgery for recurrent disease; pre-registration contrast MRI should confirm;
(i)progressive or recurrent glioblastoma; (ii)no evidence of acute or subacute cerebral hemorrhage at enrolment; (iii)presence of a measurable lesion.
3) For patients who underwent surgery for recurrent disease;
(i)progressive or recurrent glioblastoma must be confirmed on contrast MRI before reoperation; (ii)glioblastoma or anaplastic astrocytoma must be histologically identified in the tissue resected at reoperation; (iii)presence of measurable lesions is not mandatory on pre-registration contrast MRI (more than 4 days after reoperation); (iv)no MRI evidence of aggravating cerebral hemorrhage.
4) No evidence of tumors in the cerebellum, brain stem, optic nerve, olfactory nerve, and pituitary gland.
5) No evidence of meningeal dissemination or gliomatosis cerebri.
6) Prior treatment for newly-diagnosed glioblastoma (or anaplastic astrocytoma) with postoperative TMZ administered concomitantly with radiotherapy (>=54 Gy for <=69 years old; >=30 Gy for >=70 years old) and at least for two cycles (5/28d) as an adjuvant treatment have been given.
7) No history of prior treatment with stereotactic radiotherapy (ex. Gamma-knife/Cyberknife), proton beam irradiation, neutron capture therapy, and chemotherapies except standard dose TMZ and intraoperative placement of carmustine wafers for glioblastoma.
8) More than 90 days after completion of radiotherapy. For those who underwent reoperation, between 21 and 28 days postoperatively.
9) Age between 20 and 75 years at enrolment.
10) KPS >= 60 within 14 days before enrolment.
11) No prior treatment with chemotherapy, molecular targeted therapy, or radiotherapy to head and neck area for other malignancies.
12) Adequate organ function.
13) Written informed consent.

Key exclusion criteria

1) Synchronous or metachronous (within 5 years) malignancy, except for carcinoma in situ or mucosal tumors curatively treated with local therapy
2) Active infection requiring systemic therapy
3) Body temperature >= 38 degrees Celsius at registration
4) Women during pregnancy, possible pregnancy, within 28 days after delivery, or breast-feeding
5) Psychosis or with psychotic symptom
6) Continuous systemic use of immunosuppressant except for steroid
7) Uncontrolled diabetes mellitus or routine administration of insulin
8) Unstable angina within 3 weeks, with a history of myocardial infarction within 6 months, or New York Heart Association (NYHA) class II or greater congestive heart failure
9) Inadequately controlled hypertension (cannot be controlled to a systolic pressure of >= 150 mmHg and a diastolic pressure of >= 100 mmHg)
10) History of symptomatic cerebrovascular disorder (including subarachnoid hemorrhage, cerebral infarction and transient ischemic attack) within 6 months or history of vascular disorder requiring intervention (including venous/arterial thrombosis or embolism and aortic aneurysm) within 6 moths
11) History of grade >= 2 hemoptysis within 28 days
12) History of hemorrhagic tendency (e.g., coagulation disorder) or any grade >= 3 hemorrhage within 28 days
13) History of gastrointestinal perforation, fistula, abdominal abscess or uncontrolled peptic ulcer within 6 months
14) Interstitial pneumonia, pulmonary fibrosis, or severe lung emphysema
15) Severe non-healing wound or traumatic fracture at enrolment
16) Hypersensitivity to CHO-derived drugs or other recombinant antibodies
17) Gadolinium allergy
18) Positive HIV antibody
19) Positive HBs antigen

Target sample size

210

Name of lead principal investigator

1st name
Middle name
Last name	Motoo Nagane

Organization

Kyorin University Faculty of Medicine

Division name

Department of Neurosurgery

Zip code

Address

6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan

TEL

0422-47-5511(ext2883)

Email

mnagane@ks.kyorin-u.ac.jp

Name of contact person

1st name
Middle name
Last name	Keiichi Kobayashi

Organization

JCOG1308C Coordinating Office

Division name

Kyorin University Faculty of Medicine, Department of Neurosurgery

Zip code

Address

6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan

TEL

0422-47-5511(ext7649)

Homepage URL

http://www.jcog.jp/

Email

JCOG_sir@ml.jcog.jp

Institute

Japan Clinical Oncology Group (JCOG)

Institute

Department

Personal name

Organization

National Cancer Center

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

YES

Study ID_1

NCT02761070

Org. issuing International ID_1

ClinicalTrials.gov

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

北海道大学病院（北海道）
中村記念病院（北海道）
弘前大学医学部附属病院（青森県）
岩手医科大学（岩手県）
東北大学病院（宮城県）
山形大学医学部（山形県）
筑波大学医学医療系（茨城県）
獨協医科大学病院（栃木県）
埼玉医科大学国際医療センター（埼玉県）
千葉大学医学部（千葉県）
国立がん研究センター中央病院（東京都）
日本大学医学部附属板橋病院（東京都）
杏林大学医学部（東京都）
慶應義塾大学病院（東京都）
東京医科歯科大学（東京都）
東京大学医学部（東京都）
北里大学医学部（神奈川県）
新潟大学医歯学総合病院（新潟県）
静岡県立静岡がんセンター（静岡県）
名古屋大学医学部（愛知県）
藤田保健衛生大学（愛知県）
京都大学医学部附属病院（京都府）
大阪大学医学部（大阪府）
大阪国際がんセンター（大阪府）
関西医科大学附属病院（大阪府）
神戸大学医学部（兵庫県）
岡山大学病院（岡山県）
広島大学病院（広島県）
愛媛大学医学部附属病院（愛媛県）
九州大学病院（福岡県）
熊本大学医学部（熊本県）
鹿児島大学医学部・歯学部附属病院（鹿児島県）

Date of disclosure of the study information

2016

Year

07

Month

11

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

2015

Year

03

Month

19

Day

Date of IRB

Anticipated trial start date

2016

Year

07

Month

11

Day

Last follow-up date

2023

Year

07

Month

11

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Advanced Medical Care B

Registered date

2016

Year

07

Month

11

Day

Last modified on

2018

Year

02

Month

27

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000024791