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Neurofibromatosis 1Phase 2NCT06621082

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

A Phase 2 study testing Selumetinib in people with Neurofibromatosis 1, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neurofibromatosis 1
What is being tested?
Selumetinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
No sites listed yet
Study dates
30 Sep 2024to 31 Dec 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥18 years old
  • 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
Show all 16Show fewer
  • Before admission, the head and neck surgeon conducted pathological biopsy of solid tumors, confirmed pathological diagnosis and eliminated malignant peripheral schwannoma (MPNST).
  • There was at least one measurable tumor lesion according to the solid tumor efficacy evaluation criteria RECIST 1.1
  • The tumor did not invade the brain, spine and other important organs, there are indications of surgical resection and surgical treatment
  • The performance of the Eastern Cooperative Oncology Group (ECOG) was 0-1
  • 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).
  • 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.
  • 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.
  • Cardiac function: creatine phosphokinase ≤200U/L, left ventricular ejection fraction (LVEF) ≥50%;
  • Have not participated in other clinical trials within the past 30 days;
  • Patients who voluntarily participate in the project and sign informed consent.

Who cannot join

  • 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
  • The patient has become malignant peripheral schwannoma (MPNST) or is accompanied by other malignant tumors, heart disease and other serious complications, or has previously received chemotherapy, radiotherapy and other anti-tumor therapy
  • Unable to complete the entire clinical study due to personal, social and economic reasons
  • there is a serious systemic disease in the past and the disease cannot be cured or controlled by medicine at present
  • Pregnant patients

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Zhiquan Huang, doctoral contact

13826142898 ext. 86

hzhquan@mail.sysu.edu.cn

Zixian Huang, doctoral contact

15018754725 ext. 86

258001917@qq.com

About this study

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

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.

Read the 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.

Being tested
Selumetinib
Medical subject headings
Neurofibromatosis 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SelumetinibDrug

    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

Study groups in NCT06621082
Study groupRoleWhat they receive
Postoperative drug groupExperimentalThis study started from the recruitment of subjects, confirmed diagnosis by clinical diagnosis and pathological biopsy, preliminary screening according to inclusion and exclusion criteria, and signing of informed consent. Patients who were evaluated as indications for surgical resection and underwent surgical treatment were treated with Smetinib bisulfate capsules. PFS, ORR, and DOR were evaluated after 6 cycles of administration of Simetinib bisulfate capsules (20-50mg bid) daily for 30 days, as individualized by patient body surface area (BSA).
Receives: Drug: Selumetinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 2-year progression-free survival (2-year PFS rate)

    Refers to the rate of postoperative patients who are free of tumor progression or death from any cause (whichever occurs first) within 2 years from the start of treatment in the trial.

    Measured: Within 2 years from the start of treatment in the trial

Secondary outcomes (2)

  1. Duration of remission

    Refers to the time from the first evaluation of a tumor as CR or PR to the first evaluation as PD or death from any cause

    Measured: Within 2 years from the start of treatment in the trial

  2. Objective response rate

    The proportion of patients whose tumors shrink by ≥ 20% for a certain period of time, including complete response (CR) and partial response (PR) cases. ORR was defined as the proportion of patients whose tumor size decreased by ≥ 20% in the shortest time.

    Measured: Within 2 years from the start of treatment in the trial

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Oct 2024
  2. Study start30 Sep 2024 (estimated)
  3. Primary completion30 Nov 2026 (estimated)
  4. Study completion31 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
19 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06621082
Sponsor's protocol ID
SYSKY-2024-284-02
Status last verified
Sep 2024
First submitted
20 Aug 2024
Last updated
1 Oct 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Ly KI, Blakeley JO. The Diagnosis and Management of Neurofibromatosis Type 1. Med Clin North Am. 2019 Nov;103(6):1035-1054. doi: 10.1016/j.mcna.2019.07.004.

    PubMed 31582003

  • Gutmann DH, Ferner RE, Listernick RH, Korf BR, Wolters PL, Johnson KJ. Neurofibromatosis type 1. Nat Rev Dis Primers. 2017 Feb 23;3:17004. doi: 10.1038/nrdp.2017.4.

    PubMed 28230061

  • Di Rocc C, Samii A, Tamburrini G, Massimi L, Giordano M. Sphenoid dysplasia in neurofibromatosis type 1: a new technique for repair. Childs Nerv Syst. 2017 Jun;33(6):983-986. doi: 10.1007/s00381-017-3408-z. Epub 2017 Apr 13.

    PubMed 28409229

  • Miller DT, Freedenberg D, Schorry E, Ullrich NJ, Viskochil D, Korf BR; COUNCIL ON GENETICS; AMERICAN COLLEGE OF MEDICAL GENETICS AND GENOMICS. Health Supervision for Children With Neurofibromatosis Type 1. Pediatrics. 2019 May;143(5):e20190660. doi: 10.1542/peds.2019-0660.

    PubMed 31010905

  • Blakeley JO, Plotkin SR. Therapeutic advances for the tumors associated with neurofibromatosis type 1, type 2, and schwannomatosis. Neuro Oncol. 2016 May;18(5):624-38. doi: 10.1093/neuonc/nov200. Epub 2016 Feb 6.

    PubMed 26851632

  • Friedrich RE, Schmelzle R, Hartmann M, Funsterer C, Mautner VF. Resection of small plexiform neurofibromas in neurofibromatosis type 1 children. World J Surg Oncol. 2005 Jan 31;3(1):6. doi: 10.1186/1477-7819-3-6.

    PubMed 15683544

  • Prada CE, Rangwala FA, Martin LJ, Lovell AM, Saal HM, Schorry EK, Hopkin RJ. Pediatric plexiform neurofibromas: impact on morbidity and mortality in neurofibromatosis type 1. J Pediatr. 2012 Mar;160(3):461-7. doi: 10.1016/j.jpeds.2011.08.051. Epub 2011 Oct 11.

    PubMed 21996156

  • Martin S, Wolters P, Baldwin A, Gillespie A, Dombi E, Walker K, Widemann B. Social-emotional functioning of children and adolescents with neurofibromatosis type 1 and plexiform neurofibromas: relationships with cognitive, disease, and environmental variables. J Pediatr Psychol. 2012 Aug;37(7):713-24. doi: 10.1093/jpepsy/jsr124. Epub 2012 Feb 21.

    PubMed 22353803

  • Ferner RE, Huson SM, Thomas N, Moss C, Willshaw H, Evans DG, Upadhyaya M, Towers R, Gleeson M, Steiger C, Kirby A. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet. 2007 Feb;44(2):81-8. doi: 10.1136/jmg.2006.045906. Epub 2006 Nov 14.

    PubMed 17105749

  • Anderson MK, Johnson M, Thornburg L, Halford Z. A Review of Selumetinib in the Treatment of Neurofibromatosis Type 1-Related Plexiform Neurofibromas. Ann Pharmacother. 2022 Jun;56(6):716-726. doi: 10.1177/10600280211046298. Epub 2021 Sep 18.

    PubMed 34541874

  • Harder A. MEK inhibitors - novel targeted therapies of neurofibromatosis associated benign and malignant lesions. Biomark Res. 2021 Apr 16;9(1):26. doi: 10.1186/s40364-021-00281-0.

    PubMed 33863389

  • Campagne O, Yeo KK, Fangusaro J, Stewart CF. Clinical Pharmacokinetics and Pharmacodynamics of Selumetinib. Clin Pharmacokinet. 2021 Mar;60(3):283-303. doi: 10.1007/s40262-020-00967-y. Epub 2020 Dec 23.

    PubMed 33354735

  • Gross AM, Wolters PL, Dombi E, Baldwin A, Whitcomb P, Fisher MJ, Weiss B, Kim A, Bornhorst M, Shah AC, Martin S, Roderick MC, Pichard DC, Carbonell A, Paul SM, Therrien J, Kapustina O, Heisey K, Clapp DW, Zhang C, Peer CJ, Figg WD, Smith M, Glod J, Blakeley JO, Steinberg SM, Venzon DJ, Doyle LA, Widemann BC. Selumetinib in Children with Inoperable Plexiform Neurofibromas. N Engl J Med. 2020 Apr 9;382(15):1430-1442. doi: 10.1056/NEJMoa1912735. Epub 2020 Mar 18.

    PubMed 32187457

  • Dombi E, Baldwin A, Marcus LJ, Fisher MJ, Weiss B, Kim A, Whitcomb P, Martin S, Aschbacher-Smith LE, Rizvi TA, Wu J, Ershler R, Wolters P, Therrien J, Glod J, Belasco JB, Schorry E, Brofferio A, Starosta AJ, Gillespie A, Doyle AL, Ratner N, Widemann BC. Activity of Selumetinib in Neurofibromatosis Type 1-Related Plexiform Neurofibromas. N Engl J Med. 2016 Dec 29;375(26):2550-2560. doi: 10.1056/NEJMoa1605943.

    PubMed 28029918

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Selumetinib in people with Neurofibromatosis 1, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 1 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Zhiquan Huang, doctoral (13826142898 ext. 86, hzhquan@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

2-year progression-free survival (2-year PFS rate) (time frame: Within 2 years from the start of treatment in the trial). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06621082, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2024.

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