Clinical Study on the Treatment of Type I Neurofibromatosis With Smeitinib Hydrosulfate Capsule

This study focused on patients with type I neurofibromatosis, who currently lack effective drug therapy and have a high recurrence rate after surgical resection. As a MEK inhibitor, Smetinib bisulfate capsule can induce tumor shrinkage by selectively binding mitogen-activated protein kinase (MEK) 1/2 protein, blocking the mitogen-activated protein kinase/extracellular signal regulatory kinase signaling pathway that regulates key cell responses. To create conditions for disease control, radical surgical resection, reducing postoperative recurrence and reducing complications. The purpose of this study was to provide treatment with Smetinib bisulfate for patients with type I neurofibromatosis, observe the therapeutic effect in stages, convert patients without surgical indications into patients with surgical indications, increase the proportion of surgical resection and reduce the recurrence rate. Objective tumor response rate (ORR) after drug treatment was used as the main outcome index in this study. The resectable scope, duration of remission (DOR), progression-free survival (PFS) were used as secondary outcome indicators to investigate the improvement of resectable rate, reduction of resectable scope and postoperative complications, tumor shrinkage effect, and the stability of curative effect of the use of smetinib bisulfate capsule on type I neurofibromatosis.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

1. Age ≥18 years old
2. According to the National Institutes of Health (NIH) updated diagnostic criteria for NF1 in 2021, 6 or more CALMs: d\>5 mm before puberty or d\>15 mm after puberty; 2 or more neurofibromas of any type or 1 plexiform neurofibroma;

   ③ Freckles in the armpit or groin area;

   ④ optic glioma (OPG);

   ⑤ Two or more Lisch nodules were detected by slit-lamp, or two or more choroidal abnormalities were detected by optical coherence tomography (OCT)/ near-infrared (NIR) imaging;

   ⑥ Characteristic bone lesions, such as sphenoid dysplasia, anterolateral tibial curvature; Pathogenic heterozygote NF1 variant with 50% allele variant fraction in normal tissues (such as white blood cells); NF1 is diagnosed in persons who have no history of parental disease and meet 2 or more clinical characteristics Individuals with a history of parental disease who meet one or more clinical characteristics may be diagnosed with NF1
3. Before admission, the head and neck surgeon conducted pathological biopsy of solid tumors, confirmed pathological diagnosis and eliminated malignant peripheral schwannoma (MPNST).
4. There was at least one measurable tumor lesion according to the solid tumor efficacy evaluation criteria RECIST 1.1
5. The tumor invaded the brain, spine and other important organs, no indication of surgical resection
6. The performance of the Eastern Cooperative Oncology Group (ECOG) was 0-1
7. Blood routine: white blood cell count (WBC) ≥3.0×109/L; Absolute neutrophil count (ANC) ≥ 1.5×109/L; Platelet (PLT) ≥ 100×109/L; Hemoglobin level (HGB) ≥ 9.0 g/dL (7 days without corresponding supportive treatment, such as blood transfusion and increased white blood cells).
8. Liver function: the patient's aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were less than 2.5 times the upper limit of reference value (ULN); Albumin (ALB) ≥ 30 g/L.
9. Renal function: serum creatinine ≤1.5 times ULN or creatinine clearance (CrCl) ≥ 50mL/min (using Cockcroft/Gault formula); Urinary protein (UPRO) \< (++), or 24-hour urinary protein volume \< 1.0 g.
10. Cardiac function: creatine phosphokinase ≤200U/L, left ventricular ejection fraction (LVEF) ≥50%;
11. Have not participated in other clinical trials within the past 30 days;
12. Patients who voluntarily participate in the project and sign informed consent.

Exclusion Criteria:

1. The patient had abnormal blood indexes and abnormal liver, kidney and heart function, and could not tolerate the clinical study process after multidisciplinary consultation and evaluation
2. Patients have malignant peripheral schwannoma (MPNST) or other malignant tumors, heart disease and other serious complications, or have previously undergone anti-tumor therapy such as surgery, chemotherapy, radiotherapy
3. Unable to complete the entire clinical study due to personal, social and economic reasons
4. there is a serious systemic disease in the past and the disease cannot be cured or controlled by medicine at present
5. Pregnant patients

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