UMIN-CTR Clinical Trial
| Unique ID issued by UMIN | UMIN000018261 |
|---|---|
| Receipt number | R000021126 |
| Scientific Title | Combination of bevacizumab plus nimustine in patients with post-temozolomide recurrent or progressive high-grade glioma |
| Date of disclosure of the study information | 2015/07/10 |
| Last modified on | 2024/03/13 12:26:32 |
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Basic information
Public title
Combination of bevacizumab plus nimustine in patients with post-temozolomide recurrent or progressive high-grade glioma
Acronym
Bevacizumab plus nimustine (BEVAC) for recurrent high grade glioma
Scientific Title
Combination of bevacizumab plus nimustine in patients with post-temozolomide recurrent or progressive high-grade glioma
Scientific Title:Acronym
Bevacizumab plus nimustine (BEVAC) for recurrent high grade glioma
Region
| Japan |
Condition
Condition
Recurrent glioblastoma or anaplastic glioma after induction therapy
Classification by specialty
| Neurosurgery |
Classification by malignancy
Malignancy
Genomic information
NO
Objectives
Narrative objectives1
Standard of care for patients with glioblastoma (GBM) (and also high grade glioma in community practice) is postsurgical chemoradiotherapy with temozolomide followed by temozolomide monotherapy. Yet these tumors eventually recur and the median survival time (MST) for GBM remains ~15 months. Standard therapy for recurrent GBM has not been established, but since approval of bevacizumab (BEV), BEV monotherapy has been widely used as the second line therapy. However, survival benefit of BEV monotherapy is limited with MST being 8-10 months. In order to improve outcome of BEV therapy, many combination regimens with BEV have been explored, but most of them have failed to show elongation of survival except for one study, BELOB trial, which combined lomustine (CCNU) with BEV against recurrent GBM. In that trial, combination of BEV with lomustine was superior to either BEV or lomustine alone in both OS-9m and PFS-6m. Currently, a phase III trial EORTC26101 is ongoing investigating efficacy of BEV plus lomustine combination over lomustine alone for patients with GBM at first relapse in Europe. In Japan, lomustine has not been approved or sold. Instead, nimustine (ACNU), another chloroethylnitrosourea agent like lomustine developed in Japan, was approved for glioma in 1980 and has been widely used since then. Based on these situations, we plan to investigate the efficacy and safety of combination of BEV plus nimustine for high-grade glioma in the recurrent settings after initial temozolomide therapy.
Basic objectives2
Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Exploratory
Trial characteristics_2
Others
Developmental phase
Phase II
Assessment
Primary outcomes
6 months progression-free survival
Key secondary outcomes
Overall survival, progression-free survival, complete response rate, overall response rate (ORR), adverse event rate, serious adverse event rate
Base
Study type
Interventional
Study design
Basic design
Single arm
Randomization
Non-randomized
Randomization unit
Blinding
Open -no one is blinded
Control
Historical
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment
Intervention
No. of arms
1
Purpose of intervention
Treatment
Type of intervention
| Medicine |
Interventions/Control_1
Bevacizumab + nimustine (ACNU)
Bevacizumab: 10 mg/kg div, day 1, 15, 29
ACNU: 60 mg/m2 iv, day 1
in 42-day cycle, for 6 cycles.
From 7th cycle, continue bevacizumab 10 mg/kg alone every 2 weeks.
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
| 20 | years-old | <= |
Age-upper limit
| Not applicable |
Gender
Male and Female
Key inclusion criteria
1) Age >= 20.
2) Expected to live more than 3 months.
3) Progressive or recurrent high-grade glioma documented by contrast MRI or CT (second or more recurrence is allowed)
4) Histologically proven diagnosis of glioblastoma or anaplastic glioma.
5) Prior treatment with TMZ and radiotherapy.
6) Patients who did not undergo surgery for recurrent disease must be enrolled within 14 days of the last radiological confirmation of progression with measurable lesions (diameter >= 0.5 cm) on contrast MRI or CT. Measurable lesions are not required for those who underwent surgery for recurrent disease.
7) Baseline contrast MRI or CT should be taken 1) 2 weeks or more after surgery (protocol treatment needs to be started after 28 days from surgery), 2) 5 days or more after fixation of corticosteroid dose.
8) No MRI evidence of acute or subacute cerebral hemorrhage at enrolment. Enrolment will, however, be permitted in the following cases: presence of hemosiderin; resolving hemorrhagic changes related to surgery at pre-enrolment MRI; and presence of punctuate hemorrhage in the tumor in the absence of clinical symptoms.
9) PS 0 - 2 at enrolment. PS 3 due to neurological deficits may be eligible.
10) Adequate laboratory data by the latest testing performed within 2 weeks prior to enrolment.
11) Written consent is obtained from the patient him/herself, or by his/her family members.
12) Patient who can be followed up.
Key exclusion criteria
1) Active cancers in other organs.
2) Concurrent infectious diseases necessitate systemic treatment.
3) Patients who are pregnant, willing to be pregnant, within 28 days postpartum, or actively breastfeeding.
4) Male patients who will not prevent conception during protocol treatment.
5) Concurrent psychiatric disorders judged to be ineligible to enrolment.
6) Those under continuous systemic immunosuppressive treatment except for corticosteroids.
7) Those under treatment with continual use of insulin or with the complication of uncontrolled diabetes mellitus or peptic ulcer.
8) Evidence of unstable angina or history of cardiac infarction within 6 months.
9) Inadequately controlled hypertension at time of enrolment.
10) Current or prior hypertensive crisis or hypertensive encephalopathy.
11) New York Heart Association (NYHA) class II or greater congestive heart failure at enrolment.
12) History of symptomatic cerebrovascular disorder (including subarachnoid hemorrhage, cerebral infarction and transient ischemic attack) within 6 months prior to enrolment.
13) Current or history of vascular diseases (including venous/arterial thromboembolism, aortic aneurysms) requiring treatment within 6 months prior to enrolment.
14) History of grade >= 2 hemoptysis within 1 month prior to enrolment.
15) Hemorrhagic tendency (e.g., coagulation disorder) at enrolment or history of grade 3 or greater hemorrhagic events within 1 month prior to enrolment.
16) History of gastrointestinal perforation, fistula or abdominal abscess within 6 months prior to enrolment.
17) Concurrent pulmonary fibrosis, interstitial pneumonia, or high-grade emphysema.
18) Patients with severe non-healing wound or traumatic fracture at enrolment.
19) History of hypersensitivity to CHO-derived drugs or other recombinant antibodies.
20) HIV positive or HBV-Ag positive.
21) Those who are judged inappropriate for enrolment to this study by the physician.
Target sample size
32
Research contact person
Name of lead principal investigator
| 1st name | Motoo |
| Middle name | |
| Last name | Nagane |
Organization
Kyorin University Faculty of Medicine
Division name
Department of Neurosurgery
Zip code
181-8611
Address
6-20-2 Shinkawa, Mitaka, Tokyo, JAPAN
TEL
0422-47-5511
mnagane@ks.kyorin-u.ac.jp
Public contact
Name of contact person
| 1st name | Keiichi |
| Middle name | |
| Last name | Kobayashi |
Organization
Kyorin University Faculty of Medicine
Division name
Department of Neurosurgery
Zip code
181-8611
Address
6-20-2 Shikawa, Mitaka, Tokyo, JAPAN
TEL
0422-47-5511
Homepage URL
kekobayashi@kki.biglobe.ne.jp
Sponsor or person
Institute
Department of Neurosurgery, Kyorin University Faculty of Medicine
Institute
Department
Personal name
Funding Source
Organization
Department research fund from Kyorin University
Organization
Division
Category of Funding Organization
Self funding
Nationality of Funding Organization
Japan
Other related organizations
Co-sponsor
Department of Neurosurgery, The University of Tokyo
Name of secondary funder(s)
IRB Contact (For public release)
Organization
Faculty of Medicine Research Ethics Committee, Kyorin University
Address
6-20-2 Shinkawa, Mitaka, Tokyo
Tel
0422-47-5511
irb@ks.kyorin-u.ac.jp
Secondary IDs
Secondary IDs
NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW
Institutions
Institutions
杏林大学医学部付属病院脳神経外科/Kyorin University Hospital
東京大学医学部附属病院/The University of Tokyo Hospital
Other administrative information
Date of disclosure of the study information
| 2015 | Year | 07 | Month | 10 | Day |
Related information
URL releasing protocol
unpublished
Publication of results
Unpublished
Result
URL related to results and publications
unpublished
Number of participants that the trial has enrolled
22
Results
To be reported.
Results date posted
| 2024 | Year | 03 | Month | 03 | Day |
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
To be reported.
Participant flow
To be reported.
Adverse events
To be reported.
Outcome measures
Primary endpoint: 6-month progression-free survival rate (PFS-6m)
Secondary endpoints: Overall survival (OS) after initiation of treatment, progression-free survival (PFS), complete response rate (CR), overall response rate (ORR), incidence of adverse events, incidence of serious adverse events
Plan to share IPD
IPD sharing Plan description
Progress
Recruitment status
Completed
Date of protocol fixation
| 2014 | Year | 05 | Month | 01 | Day |
Date of IRB
| 2014 | Year | 05 | Month | 01 | Day |
Anticipated trial start date
| 2014 | Year | 05 | Month | 01 | Day |
Last follow-up date
| 2021 | Year | 04 | Month | 30 | Day |
Date of closure to data entry
Date trial data considered complete
| 2023 | Year | 12 | Month | 22 | Day |
Date analysis concluded
| 2024 | Year | 03 | Month | 13 | Day |
Other
Other related information
Management information
Registered date
| 2015 | Year | 07 | Month | 09 | Day |
Last modified on
| 2024 | Year | 03 | Month | 13 | Day |
Link to view the page
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000021126
