NCT06621082

The Clinical Study of the Treatment of Patients With Type I Neurofibromatosis With Smetinib Hydrosulfate Capsule

A Prospective, One-arm, Phase II Clinical Study of Smeitinib Hydrosulfate Capsules for the Treatment of Patients With Type I Neurofibromatosis After Surgery

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 19 (estimated)
• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study focused on patients with type I neurofibromatosis undergoing surgical treatment, who currently lack effective drug therapy and have a high recurrence rate after surgical resection. For patients with small solid tumors, limited space, and no invasion of the brain, spine and other important organs, surgical treatment is the main treatment. As a MEK inhibitor, Smetinib bisulfate capsule can induce tumor shrinkage and reduce postoperative recurrence by selectively binding mitogen-activated protein kinase (MEK) 1/2 protein to block the mitogen-activated protein kinase/extracellular signal regulatory kinase signaling pathway that regulates key cell responses. The purpose of this study was to treat patients with type I neurofibromatosis with indications of surgery with the drug smetinib bisulfate after surgical treatment, observe the therapeutic effect of the drug in stages, consolidate the postoperative effect and reduce the recurrence rate. In this study, progression-free survival (PFS) after postoperative drug treatment was used as the main outcome index, and duration of remission (DOR) and objective response rate (ORR) were used as secondary outcome indicators to investigate the efficacy of the use of Smetinib hydrosulfate capsule on tumor control, reduction of recurrence rate and stability of efficacy in patients with type I neurofibromatosis after surgery.

Detailed description

Neurofibromatosis (NF) has been included in the list of rare diseases in many countries, including China, of which 96% is NF1 subtype, NF1 clinical manifestations are diverse, involve multiple systems, can cause respiratory obstruction, spinal cord compression, motor dysfunction and other serious complications. Plexiform neurofibroma (PN) occurs in 30-50% of patients with NF1. PN progresses rapidly, is associated with severe physical defects, is highly disabling, and is at risk of malignancy. According to the 2023 edition of the Multidisciplinary Guidelines for the Diagnosis and Treatment of type I neurofibromatosis, NF1 patients are more likely than the normal population to develop a variety of benign and malignant tumors, including pNF, CNF, MPNST and OPG. Attention should be paid to the early identification and monitoring of these tumors. The possibility of MPNST should be highly vigilant for neurofibromas with growth acceleration, pain, and texture hardening. At the same time, systemic evaluation should be performed, and early surgery should be performed as far as possible for patients without signs of distant metastasis, while radiotherapy, chemotherapy and targeted therapy can be selected for patients with distant metastasis. neurofibromatosis type 1 (NF1) is an autosomal dominant disorder in which 50% of patients have familial inherited mutations and 50% have sporadic mutations. NF1 gene encodes neurofibrin, down-regulates the activity of Ras-Raf pathway, and inhibits cell proliferation. Neurofibrin defects can lead to overactivation of the RAS pathway, resulting in uncontrolled cell proliferation in patients with NF1. At present, surgery is the most commonly used and most important treatment for neurofibromatosis, and neurofibroma has the characteristic of growing along the nerve root, so it is difficult to solve all the lesions through surgery. The lesions consist of a wide range of nerve and vascular tissues mixed with normal tissues, and the surgical resection is difficult and bleeding is frequent, and the recurrence after incomplete resection is as high as 50%. For NF1 in the head and neck, some patients require a second operation one year after surgery, and the proportion of patients with partial resection undergoing a second operation is higher than that of patients with subtotal resection. Five years after surgery, more than 50% of patients needed a second operation. As a MEK inhibitor, Smetinib bisulfate capsule can induce tumor shrinkage by selectively binding mitogen-activated protein kinase (MEK) 1/2 protein to block the mitogen-activated protein kinase/extracellular signal regulatory kinase signaling pathway that regulates key cellular responses. To create conditions for disease control, radical surgical resection, reducing postoperative recurrence and reducing complications. Based on the targeted therapy of smeitinib bisulfate capsule, this study evaluated the treatment of NF1 patients after surgical treatment, and evaluated the effect of tumor shrinkage after medication by monitoring the effect and duration of solid tumor shrinkage of patients. And the postoperative recurrence time, so as to verify the effectiveness of smeitinib bisulfate capsule in reducing the recurrence rate of patients after NF1.

Conditions

• Neurofibromatosis 1

Interventions

Type	Name	Description
DRUG	Selumetinib	After surgical resection，based on the patient's body surface area (BSA), the patient was given an oral dose of Simetinib bisulfate capsule (20-50mg bid) daily for 30 days for 6 cycles

Timeline

• Start date: 2024-09-30
• Primary completion: 2026-11-30
• Completion: 2026-12-31
• First posted: 2024-10-01
• Last updated: 2024-10-01