Neurofibromatosis type 2
Conditions
Interventions
investigational material(s)
Generic name etc : Bevacizumab (Genitical Recombination)
INN of investigational material : Bevacizumab (Genitical Recombination)
Therapeutic category code : 429 Other antit
Sponsors
Kiyoshi Saito
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
Eligibility
Sex/Gender
All
Inclusion 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
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 st | — |
Countries
Japan
Outcome results
None listed