Icotinib Study for Patients With Neurofibromatosis Type 2 (NF2) and NF2-Related Tumors (Icotinib)

• Sponsor: Li Peng
• Collaborator: Betta Pharmaceuticals Co., Ltd.
• Information provided by (Responsible Party): Li Peng, Beijing Tiantan Hospital

Study Description

Brief Summary:

1)Preliminarily evaluate the treatment effect of Icotinib Hydrochloride Tablets on NF2; 2)Preliminarily evaluate the safety and the patient's tolerance of the treatment of Icotinib; 3)Provide an objective basis for an enlarged randomized double-blind trial.

Condition or disease	Intervention/treatment	Phase
Vestibular Schwannoma; Neurofibromatosis Type 2	Drug: Icotinib	Phase 2

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 Erlotinib suggested that inhibition of epidermal growth factor receptor (EGFR) could result in hearing improvement and reduction in tumor size.

Much evidence implicates human epidermal growth factor (HER) receptors in vestibular schwannoma growth.Some studies have demonstrated that Merlin, the NF2 gene protein product, controls surface availability of the EGFR, ErbB2, and ErbB3 receptors in human and Drosophila models. Besides, cell culture models of mouse embryo fibroblasts (MEFs) support the role of EGFR in NF2-associated tumorigenesis. Nf2-deficient cells in culture lack contact-dependent inhibition of growth and continue to grow in confluent cultures. This effect appears to be mediated by EGFR signaling. Treatment of Nf2-deficient cells with EGFR inhibitors such as gefitinib can restore contact-dependent inhibition, suggesting that this class of drugs might be useful for NF2 patients with progressive vestibular schwannomas. In this way, Icotinib can inhibit the nutrition of the tumor and decrease the tumor's growth and metastasis. Based on these studies, we perform this clinical trial to known the treatment effect and tolerability of Icotinib on NF2.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	20 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Icotinib Hydrochloride Tablets Study for Patients With Neurofibromatosis Type 2 (NF2) and NF2-Related Tumors
Study Start Date :	July 2016
Estimated Primary Completion Date :	January 2018
Estimated Study Completion Date :	June 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Icotinib，treatment effect evaluation; Patients use Icotinib hydrochloride tablets during the course of treatment. The drug dosage is 125mg/m3/d. Every course of treatment lasts three months. Patients are designed to receive total four courses of treatment if there is no disease progression.	Drug: Icotinib; Method of drug administration:oral; Dosage: 125mg/m3/d; Course of treatment: 3 months;Total four treatment courses.; Other Name: Icotinib Hydrochloride Tablets

Outcome Measures

Primary Outcome Measures :

1. Change from Baseline in volume of tumour after every course of the treatment [ Time Frame: Baseline,Month 3,Month 6,Month 9,Month 12 ]
   Patients in this clinical trial would receive MRI test to evaluate the volume of tumour after every course of the treatment.

Secondary Outcome Measures :

1. Change from Baseline in hearing ability after every course of the treatment [ Time Frame: Baseline,Month 3,Month 6,Month 9,Month 12 ]
   Patients' hearing ability would be tested after every course of the treatment.

Other Outcome Measures:

1. Change from baseline in QOL(quality of life) score after every course of the treatment [ Time Frame: Baseline,Month 3,Month 6,Month 9,Month 12 ]
   Patients' QOL(quality of life) would be evaluated after every course of the treatment.

Eligibility Criteria

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Ages Eligible for Study:	16 Years to 50 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Patients must be at the age of 16-50
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.

Contacts and Locations

Contacts

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Contact: Pinan Liu	+86 010 67096865	liupinan@hotmail.com
Contact: Fu Zhao	+86 010 67096775	talentzf@hotmail.com

Locations

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China, Beijing
Beijing Tiantan Hospital Affiliated to Capital Medical University	Recruiting
Beijing, Beijing, China, 100050
Contact: Pinan Liu +86 010 67096865 liupinan@hotmail.com
Principal Investigator: Fu Zhao
China
Beijing Tiantan Hospital Affiliated to Capital Medical University	Recruiting
Beijing, China, 100050
Contact: Pinan Liu +86 010 67096865 liupinan@hotmail.com
Principal Investigator: Fu Zhao

Sponsors and Collaborators

Li Peng

Betta Pharmaceuticals Co., Ltd.

Investigators

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Study Director:	Pinan Liu	Beijing Tiantan Hospital
Principal Investigator:	Fu Zhao	Beijing Neurosurgical Institute

More Information

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Responsible Party:	Li Peng, principal investigator, Beijing Tiantan Hospital
ClinicalTrials.gov Identifier:	NCT02934256 History of Changes
Other Study ID Numbers:	Tian-drug-neuro002
First Posted:	October 14, 2016
Last Update Posted:	February 9, 2017
Last Verified:	February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

Keywords provided by Li Peng, Beijing Tiantan Hospital:

Neurofibromatosis Type 2; Vestibular Schwannoma; Other NF2-related tumors

Additional relevant MeSH terms:

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Neurofibromatoses; Neurofibromatosis 1; Neurofibroma; Neurilemmoma; Neuroma, Acoustic; Neurofibromatosis 2; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases	Genetic Diseases, Inborn; Peripheral Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neuroma; Cranial Nerve Neoplasms; Neoplasms by Site; Vestibulocochlear Nerve Diseases; Retrocochlear Diseases; Ear Diseases; Otorhinolaryngologic Diseases