Clinical trial NCT02104323: Endostatin Study for Patients With Neurofibromatosis Type 2 (NF2) and NF2-Related Tumors
Official title: Recombinant Human Endostatin Injection Study for Patients With Neurofibromatosis Type 2 (NF2) and NF2-Related Tumors by Continuous Intravenous Pumping
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Vestibular Schwannoma
Neurofibromatosis Type 2
Keywords: Neurofibromatosis Type 2
Vestibular Schwannoma
Other NF2-related tumors
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
Collaborators: name: Shandong Simcere-Medgenn Bio-pharmaceutical Co., Ltd
First posted: 2014-04-04
Enrollment: 20
Sex: ALL
Minimum age (years): 16
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 1)Preliminarily evaluate the treatment effect of continuous vein injection of recombinant human endostatin on NF2; 2)Preliminarily evaluate the safety and the patient's tolerance of the treatment of endostatin; 3)Provide an objective basis for an enlarged randomized double-blind trial.

Detailed description: Neurofibromatosis type 2 (NF2) is a hereditary tumor predisposition syndrome caused by mutations in the NF2 tumor suppressor gene. Individuals with NF2 have a higher likelihood to develop multiple nervous system tumors, including schwannomas, meningiomas, and ependymomas. The hallmark of NF2 is bilateral vestibular schwannomas. Historically, most NF2 patients experience complete hearing loss either from tumor progression or after treatment of the tumors with surgery or radiation. Effective treatments are urgently needed for NF2 patients with progressive hearing loss because hearing loss is associated with impairment in social, emotional,and communication function and with increased depression.

Previous studies of NF2 patients treated with bevacizumab suggested that inhibition of vascular endothelial growth factor (VEGF) could result in hearing improvement and reduction in tumor size.Recombinant human endostatin can inhibit the formation of blood vessels by inhibiting the migration of vascular endothelial cells .In this way, endostatin can inhibit the nutrition of the tumor and decrease the tumor's growth and metastasis. In vitro tests, endostatin can inhibit the cell migration and Tube formation of the microvascular endothelial cell line HHEC. Besides, it can inhibit blood vessels' formation of the chicken embryo sac membrane. Based on these studies, we perform this clinical trial to known the treatment effect and tolerability of endostatin on NF2.

Eligibility criteria: Inclusion Criteria:

* 1)Patients must be at the age of 16-30
* 2)Patients must meet the diagnostic criteria for NF2, with bilateral acoustic neuroma and other central nervous system tumors
* 3)Patients must not be treated with other drugs or radiation therapy recently
* 4)Patients should live in Beijing or nearby and can be treated in hospital
* 5)Patients must be healthy and not be seriously allergic with biological agents
* 6)Patients must join the clinical trial voluntarily, with good compliance, cooperate with the researchers well, sign a written informed consent.

Exclusion Criteria:

* 1)Treated with other drugs, surgery or radiation therapy recently
* 2)Brainstem is compressed seriously, with hydrocephalus, need to be treated with surgery in short time
* 3)Being pregnant or try to get pregnant, lactating women
* 4)With acute or chronic infectious diseases
* 5)With heart diseases, cardiac dysfunction or abnormal ECG
* 6)With uncontrolled neural or mental diseases, poor compliance
* 7)Not available for enhanced MRI
* 8)Take part in any other clinical trial
* 9)With other conditions that are considered not suitable for this clinical trial.

Primary outcomes:
measure: Change from Baseline in volume of tumour after every course of the treatment
timeFrame: Baseline,Month 3,Month 7,Month 11
Secondary outcomes:
measure: Change from Baseline in hearing ability after every course of the treatment
timeFrame: Baseline,Month 3,Month 7,Month 11
Other outcomes:
measure: Change from baseline in QOL(quality of life) score after every course of the treatment
timeFrame: Baseline,Month 3,Month 7,Month 11
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital Affiliated to Capital Medical University
state: Beijing
Study officials:
affiliation: Beijing Tiantan Hospital
name: Pinan Liu
role: STUDY_DIRECTOR
affiliation: Beijing Neurosurgical Institute
name: Fu Zhao
role: PRINCIPAL_INVESTIGATOR
References:
citation: Plotkin SR, Merker VL, Halpin C, Jennings D, McKenna MJ, Harris GJ, Barker FG 2nd. Bevacizumab for progressive vestibular schwannoma in neurofibromatosis type 2: a retrospective review of 31 patients. Otol Neurotol. 2012 Aug;33(6):1046-52. doi: 10.1097/MAO.0b013e31825e73f5.
citation: Plotkin SR, Stemmer-Rachamimov AO, Barker FG 2nd, Halpin C, Padera TP, Tyrrell A, Sorensen AG, Jain RK, di Tomaso E. Hearing improvement after bevacizumab in patients with neurofibromatosis type 2. N Engl J Med. 2009 Jul 23;361(4):358-67. doi: 10.1056/NEJMoa0902579. Epub 2009 Jul 8.
citation: Nunes FP, Merker VL, Jennings D, Caruso PA, di Tomaso E, Muzikansky A, Barker FG 2nd, Stemmer-Rachamimov A, Plotkin SR. Bevacizumab treatment for meningiomas in NF2: a retrospective analysis of 15 patients. PLoS One. 2013;8(3):e59941. doi: 10.1371/journal.pone.0059941. Epub 2013 Mar 21.
citation: Plotkin SR, Ardern-Holmes SL, Barker FG 2nd, Blakeley JO, Evans DG, Ferner RE, Hadlock TA, Halpin C; REiNS International Collaboration. Hearing and facial function outcomes for neurofibromatosis 2 clinical trials. Neurology. 2013 Nov 19;81(21 Suppl 1):S25-32. doi: 10.1212/01.wnl.0000435746.02780.f6.
citation: Mautner VF, Nguyen R, Kutta H, Fuensterer C, Bokemeyer C, Hagel C, Friedrich RE, Panse J. Bevacizumab induces regression of vestibular schwannomas in patients with neurofibromatosis type 2. Neuro Oncol. 2010 Jan;12(1):14-8. doi: 10.1093/neuonc/nop010. Epub 2009 Oct 20.