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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: JPRN
Last refreshed on: 4 November 2020
Main ID:  JPRN-JapicCTI-194999
Date of registration: 14/10/2019
Prospective Registration: Yes
Primary sponsor: Kiyoshi Saito
Public title: BeatNF2 trial
Scientific title: A Randomized Double-blind Multicenter trial to Assess the Efficacy and Safety of Bevacizumab for Neurofibromatosis Type 2
Date of first enrolment: 15/10/2019
Target sample size: 60
Recruitment status: pending
URL:  https://www.clinicaltrials.jp/user/showCteDetailE.jsp?japicId=JapicCTI-194999
Study type:  INTERVENTIONAL
Study design:  A Randomized Double-blind Multicenter trial  
Phase:  2
Countries of recruitment
Japan
Contacts
Name: Fukushima Medical University Department of Neurosurgery   
Address:  1 Hikarigaoka, Fukushima City, Fukushima, Japan
Telephone: +81-24-547-1111
Email: beatnf2@fmu.ac.jp
Affiliation: 
Name: Fukushima Medical University Hospital Department of Neurosurgery   
Address:  1 Hikarigaoka, Fukushima City, Fukushima, Japan
Telephone: +81-24-547-1111
Email: beatnf2@fmu.ac.jp
Affiliation: 
Key inclusion & exclusion criteria
Inclusion criteria: 1. Written informed consent must be obtained.
2. For the participants younger than 20 years old, the written informed consent must be obtained from legal representatives.
3. Male or female aged 18-64 (inclusive).
4. NF2 patients who fulfill either conditions below.
(1) have bilateral acoustic neuromas demonstrated by an MRI study
(2) have a unilateral acoustic neuroma demonstrated by an MRI study, and at least one of his/her parents, sons, daughters, brothers, sisters is diagnosed as NF2.
5. A Japanese native speaker and evaluable by the speech discrimination test in Japanese.
6. At least one side of the ear with an acoustic neuroma fulfils both conditions below.
(1) The acoustic neuroma has not been treated by radiotherapy.
(2) Hearing test of the same side of ear meets a criterion; maximum word recognition scores 80% or less, and pure tone averages less than 100dB
7. Karnofsky Performance Status greater than or equal to 60%, and general condition allows follow-up and treatment in outpatient clinic.
8. Has appropriate organ functions

Exclusion criteria: 1. History of bevacizumab treatment before this clinical trial.
2. History of VEGFR vaccine therapy.
3. A plan to undergo surgery within the coming 6 months.
4. Major surgery performed within 28 days prior to registration, or wound not healed after any kind of surgery at the time point of registration.
5. Presence of a significant traumatic injury or bone fracture that has not cured.
6. Suffering from uncontrolled hypertension at the time point of registration (unable to control blood pressure below 150 mmHg (systolic) or 110 mmHg (diastolic).
7. Presence of hypertension crisis or hypertensive encephalopathy, or past history of either of them.
8. Presence of congestive heart failure (New York Heart Association Class II or worse) at the time point of registration.
9. Presence of unstable angina or acute myocardial infarction at the time point of registration, or has past history of either of them within 6 months.
10. Presence of symptomatic cerebrovascular diseases (subarachnoid hemorrhage, cerebral infarction, or transient ischemic attack, etc.) at the time point of registration, or has past history of either of the above within 6 months.
11. Presence of vascular diseases (arterial/venous thrombosis or aortic aneurysm, etc.) that require treatments at the time point of registration, or has past history of either of them.
12. Usage or necessity of antiplatelet drugs, vitamin K antagonists, or anticoagulation drugs of any kind in a therapeutic dose.
13. Presence of hemoptysis of CTCAE grade 2 or above at the time point of registration, or has past history of it within 1 months.
14. Bleeding tendency (coagulopathy) at the time point of registration.
15. Presence of gastrointestinal perforation/fistula, or abdominal abscess at the time point of registration, or has past history of either of them within 6 months.
16. Diagnosis of cancer with disease-free periods of less than 5 years, except for cured basal cell carcinoma, squamous cell carcinoma of the skin, cervical cancer, or gastrointestinal tract cancer that has been managed and cured by endoscopic mucosal resection).
17. Presence of infectious diseases that require treatments with antibiotics, anti-viral drugs, or anti-fungal drugs at the time point of registration.
18. Allergic to drugs made from CHO or recombinant humanized antibodies.
19. Unable to do MRI.
20. The target ear is suffering from a disease other than NF2 which causes hearing loss.
21. Women who are pregnant, breastfeeding, premenopausal women who have a positive pregnancy test, or women who are not willing to use contraception during the study period. If amenorrhea has continued for more than 2 years from the last menstrual period, it is considered postmenopausal.
22. Men who are not willing to practice contraception during the study.
23. When the investigators determine that participation of the subject in this study is inappropriate.


Age minimum: 18
Age maximum: 64
Gender: BOTH
Health Condition(s) or Problem(s) studied
Neurofibromatosis type 2
Intervention(s)
Intervention name : Bevacizumab (Genitical Recombination)
INN of the intervention : Bevacizumab (Genitical Recombination)
Dosage And administration of the intervention : 5mg/kg in a total volume of 100ml, div, every 2 week
Control intervention name : Isotonic sodium chloride solution
INN of the control intervention : -
Dosage And administration of the control intervention : 100ml, div
Primary Outcome(s)
efficacy
Proportion of hearing responders at the time point of 24 weeks after starting the protocol treatment. The response is evaluated by improvement of hearing function accessed by maximum word recognition scores and defined as follows. 1. Maximum word recognition score of at least one target ear improves by 20% or greater, compared with the baseline score, and the score is 50% or above. 2. Maximum word recognition scores of target ears do not deteriorate by 20% or greater.
Secondary Outcome(s)
safety, efficacy
1. Proportion of hearing responders at the time points of 12, 36, and 48 weeks after starting the protocol treatment. The response is evaluated by improvement of hearing function accessed by maximum word recognition scores, and compared with the baseline score.
2. Proportion of hearing responders in control arm at the time points of 36, and 48 weeks after starting the protocol treatment. The response is evaluated by improvement of hearing function accessed by maximum word recognition scores, and compared with the score at the time point of 24 weeks.
3. Proportion of hearing deteriorators of non-target ear at the time point of 24 weeks after starting the protocol treatment. The response is evaluated by deterioration of hearing function accessed by maximum word recognition scores, and compared with the baseline score.
4. Proportion of tumor-volume responders at the time points of 12, 24, 36, and 48 weeks after starting the protocol treatment. The response is evaluated by tumor-volume on MRI, and compared with the baseline value.
5. Proportion of tumor-volume responders in control arm at the time points of 36 and 48 weeks after starting the protocol treatment. The response is evaluated by tumor-volume on MRI, and compared with the value at the time point of 24 weeks.
6. Estimated audiogram (average of 4 values) obtained by auditory steady state response (ASSR) examination at the time points of 12, 24 and 48 weeks after starting the protocol treatment.
7. Pure tone average (average of 4 values) at the time points of 12, 24, and 48 weeks after starting the protocol treatment
8. The severity scores of neurofibromatosis type 2 at the time points of 12, 24, 36, and 48 weeks after starting the protocol treatment.
9. Proportion of hearing responders (maximum word recognition score) at the time point of 12 weeks after starting the rechallenge treatment for the re-worsening cases.
10. Proportion of tumor-volume responders at the time point of 12 weeks after starting the for the re-worsening cases.
11. Estimated audiogram (average of 4 values) obtained by auditory steady state response (ASSR) examination at the time point of 12 weeks after starting rechallenge treatment for the re-worsening cases.
12. Pure tone average (average of 4 values) at the time point of 12 weeks after starting the rechallenge treatment for the re-worsening cases.
13. The severity scores of neurofibromatosis type 2 at the time points of 12 weeks after starting the rechallenge treatment for the re-worsening cases.
14. Safety profiles including adverse events, blood and urine examinations and vital signs.
Secondary ID(s)
Source(s) of Monetary Support
Japanese Agency for Medical Research and Development
Secondary Sponsor(s)
Masazumi Fujii, Masao Kobayakawa, Akihiro Inano, Jun Sakuma, Taku Sato, Akio Morita, Mitsuhiro Hasegawa, Takafumi Mitsuhara, Takashi Tamiya, Takeo Goro, Shigeru Yamaguchi, Hirofumi Nakatomi, Soichi Oya
Ethics review
Status: Approved
Approval date: 06/09/2019
Contact:
-
IRB of Fukushima Medical University
+81-24-547-1111
-
Results
Results available:
Date Posted:
Date Completed:
URL:
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