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

Neurofibromatosis 1 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05913037
• Other study ID #: FCN-159-007
• Status: Recruiting
• Phase: Phase 3
• Start date: June 20, 2023
• Est. completion date: June 30, 2026

Study information

• Verified date: March 2024
• Source: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.
• Contact: Wenbin Li, MD
• Phone: 15301377998
• Email: Neure55[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 162
• Est. completion date: June 30, 2026
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Neurofibroma
• Neurofibroma, Plexiform
• Neurofibromatoses
• Neurofibromatosis 1
• NF1
• Plexiform Neurofibroma

Intervention

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.
• 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.

Locations

Country	Name	City	State
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	Beijing	Beijing
China	West China Hospital,Sichuan University	Chengdu	Sichuan
China	Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	Hangzhou First People's Hospital	Hangzhou	Zhejiang
China	Zhejiang Provincial People'S Hospital	Hanzhou	Zhejiang
China	Fudan University Shanghai Cancer center	Shanghai	Shanghai
China	The First Hospial of China Medical University	Shenyang	Liaoning
China	Peking University Shenzhen Hospital	Shenzhen	Guangdong
China	The Fourth Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	The Second Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Renmin Hospital of Wuhan University	Wuhan	Hubei
China	TongJi Hospital,TongJi Medical College Huazhong University of Science and Technology	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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