FCN-159 in Adult Patients with Symptomatic, Inoperable Neurofibromatosis Type 1-Related Plexiform Neurofibromas

A Randomized, Double-Blind, Placebo-Controlled, Multi-center Phase III Clinical Study to Evaluate the Efficacy and Safety of FCN-159 in Adult Patients with Symptomatic, Inoperable Neurofibromatosis Type 1-Related Plexiform Neurofibromas

A study to evaluate the efficacy of FCN-159 in adult patients with symptomatic, inoperable neurofibromatosis type 1-related plexiform neurofibromas.

Study Overview

• Status: Active, not recruiting
• Conditions: Neurofibromatosis 1; NF1; Plexiform Neurofibroma
• Intervention / Treatment: Drug: Test group (Group A): FCN-159 8 mg, orally, once daily;; Drug: Control group (Group B): Placebo, orally, once daily

Detailed Description

This is a randomized, double-blind, placebo-controlled, multi-center phase III clinical study to evaluate the efficacy and safety of FCN-159 in adult patients with symptomatic, inoperable neurofibromatosis type 1-related plexiform neurofibromas.

• Study Type: Interventional
• Enrollment (Actual): 167
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Cancer Hospital Chinese Academy of Medical Sciences
    • Beijing, Beijing, China
      • Chinese Academy of Medical Sciences & Peking Union Medical College
    • Beijing, Beijing, China
      • Plastic Surgery Hospital,Chinese Academy of Medical Sciences
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yat-sen University Cancer Center
    • Guangzhou, Guangdong, China
      • Nanfang Hospital, Southern Medical University
    • Shenzhen, Guangdong, China
      • Peking University Shenzhen Hospital
  • Hebei
    • Shijiazhuang, Hebei, China
      • The Second Hospital of Hebei Medical University
    • Shijiazhuang, Hebei, China
      • The Fourth Hospital of Hebei Medical University
  • Hubei
    • Wuhan, Hubei, China
      • Renmin Hospital of Wuhan University
    • Wuhan, Hubei, China
      • TongJi Hospital，TongJi Medical College Huazhong University of Science and Technology
  • Liaoning
    • Shenyang, Liaoning, China
      • The First Hospial of China Medical University
  • Shanghai
    • Shanghai, Shanghai, China
      • Fudan University Shanghai Cancer Center
  • Sichuan
    • Chengdu, Sichuan, China
      • West China Hospital,Sichuan University
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Hangzhou First People's Hospital
    • Hanzhou, Zhejiang, China
      • Zhejiang Provincial People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. ≥ 18 years old and ≤ 70 years old.
2. Patients must be diagnosed with symptomatic NF1-related plexiform neurofibromas (PNs) and require systemic therapy at the investigator's discretion.
3. Presence of measurable lesions, defined as ≥ 3 cm in length in at least one dimension, which can be evaluated for efficacy by MRI.
4. Karnofsky performance status score ≥ 70.
5. Patients with adequate organ and bone marrow functions.

Exclusion Criteria:

1. NF1-related malignancies requiring chemotherapy, radiotherapy, or surgery, such as medium to high grade optic glioma or malignant peripheral nerve sheath tumor.
2. Patients with a history of or concurrently with other malignancies (excluding cured non-melanoma skin basal cell carcinoma, breast cancer in situ or cervical cancer in situ, and other malignancies without evidence of disease within 5 years).
3. Patients who cannot undergo MRI and/or have contraindications to MRI.
4. Patients with previous or current retinal vein obstruction (RVO), retinal pigment epithelial detachment (RPED), glaucoma, and other abnormal ophthalmic examination with clinical significance.
5. Interstitial pneumonia, including clinically significant radiation pneumonia.

6. Cardiac function or combined diseases meet one of the following conditions:

   1. QTcF value of > 470 milliseconds; patients with risk factors for QTcF prolongation or patients receiving drugs that prolong the QTcF interval.
   2. Congestive heart failure per New York Heart Association (NYHA) classification ≥ Class 3.
   3. Arrhythmias with clinical significance.
   4. Known concurrent clinically significant coronary artery disease, cardiomyopathy, and severe valvular disease.
   5. LVEF < 50%.
   6. Patients with a heart rate of < 50 beats/min.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FCN-159; Experimental: FCN-159 Dosage form:tablet Specification: 1mg，4mg Dose: FCN-159 8 mg, orally, once daily Method of administration: Oral	Drug: Test group (Group A): FCN-159 8 mg, orally, once daily; After completing all screening visit items, qualified patients will be randomly assigned to the test group (Group A) or control group (Group B) in a 2:1 ratio, and receive FCN-159 or placebo within 3 days after randomization.
Placebo Comparator: placebo; Experimental: placebo Dosage form:tablet Specification: 1mg，4mg Dose: placebo 8 mg, orally, once daily Method of administration: Oral	Drug: Control group (Group B): Placebo, orally, once daily; After completing all screening visit items, qualified patients will be randomly assigned to the test group (Group A) or control group (Group B) in a 2:1 ratio, and receive FCN-159 or placebo within 3 days after randomization.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) evaluated by BIRC (Response evaluation in Nerufibromatosis and Schwannomatosis, REiNS criteria)	ORR is defined as the proportion of patients who have a confirmed complete response or confirmed partial response as determined by ICR per REiNS criteria.	Through study completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) evaluated by the investigator (REiNS criteria)	ORR is defined as the proportion of patients who have a confirmed complete response or confirmed partial response as determined by ICR per REiNS criteria.	Through study completion, an average of 2 years
Duration of response (DOR) evaluated by BIRC and the investigator;	DOR is defined as the time from the date of first documented response (which is subsequently confirmed) until progression by BIRC and the investigator per REiNS criteria or death due to any cause.	Through study completion, an average of 2 years
Disease control rate (DCR) evaluated by BIRC and the investigator;	DCR is defined as the proportion of patients who have a confirmed complete response or confirmed partial response or stable disease as determined by BIRC and the investigator per REiNS criteria.	Through study completion, an average of 2 years
Clinical benefit rate (CBR)evaluated by BIRC and the investigator;	CBR is defined as the proportion of patients who have a confirmed complete response or confirmed partial response or stable disease>48 weeks as determined by BIRC and the investigator per REiNS criteria.	Through study completion, an average of 2 years
Progression free survival (PFS) evaluated by BIRC and the investigator;	PFS is defined as the time from randomization until date of disease progression by BIRC and investigator per REiNS criteria or death due to any cause.	Through study completion, an average of 2 years
Time to progression (TTP) evaluated by BIRC and the investigator;	TTP is defined as the time from randomization until date of disease progression by BIRC and investigator per REiNS criteria.	Through study completion, an average of 2 years
Time to response (TTR) evaluated by BIRC and the investigator;	TTR is defined as the time from date of randomization until the date of objective response by BIRC and investigator per REiNS criteria.	Through study completion, an average of 2 years
Change from baseline in pain intensity score	Difference in mean change from baseline in overall tumor and target PN pain intensity score between Arm A and Arm B as assessed by the 11-point Numerical Rating Scale (NRS-11),which uses the range 0-10,higher scores mean worse outcome.	Through study completion, an average of 2 years
Change from baseline in appearance	Change in appearance from baseline for Arm A versus Arm B as assessed using a sponsor-customized 'appearance evaluation'PRO questionnaire, which is descriptive.	Through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.
• Investigators: Principal Investigator: Wenbin Li, MD, Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2023
• Primary Completion (Estimated): August 19, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: June 6, 2023
• First Submitted That Met QC Criteria: June 16, 2023
• First Posted (Actual): June 22, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 4, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms; Neuromuscular Diseases; Genetic Diseases, Inborn; Peripheral Nervous System Diseases; Neoplasms by Histologic Type; Neurodegenerative Diseases; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Heredodegenerative Disorders, Nervous System; Nerve Sheath Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Peripheral Nervous System Neoplasms; Neurofibromatoses; Neurofibromatosis 1; Neurofibroma; Neurofibroma, Plexiform
• Other Study ID Numbers: FCN-159-007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No