Clinical trial NCT05913037: FCN-159 in Adult Patients With Symptomatic, Inoperable Neurofibromatosis Type 1-Related Plexiform Neurofibromas
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Neurofibromatosis 1
Plexiform Neurofibroma
NF1
Lead sponsor: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.
Sponsor class: INDUSTRY
First posted: 2023-06-22
Enrollment: 167
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Objective response rate (ORR) evaluated by BIRC (Response evaluation in Nerufibromatosis and Schwannomatosis, REiNS criteria)
timeFrame: Through study completion, an average of 2 years
Secondary outcomes:
measure: Objective response rate (ORR) evaluated by the investigator (REiNS criteria)
timeFrame: Through study completion, an average of 2 years
measure: Duration of response (DOR) evaluated by BIRC and the investigator;
timeFrame: Through study completion, an average of 2 years
measure: Disease control rate (DCR) evaluated by BIRC and the investigator;
timeFrame: Through study completion, an average of 2 years
measure: Clinical benefit rate (CBR)evaluated by BIRC and the investigator;
timeFrame: Through study completion, an average of 2 years
measure: Progression free survival (PFS) evaluated by BIRC and the investigator;
timeFrame: Through study completion, an average of 2 years
measure: Time to progression (TTP) evaluated by BIRC and the investigator;
timeFrame: Through study completion, an average of 2 years
measure: Time to response (TTR) evaluated by BIRC and the investigator;
timeFrame: Through study completion, an average of 2 years
measure: Change from baseline in pain intensity score
timeFrame: Through study completion, an average of 2 years
measure: Change from baseline in appearance
timeFrame: Through study completion, an average of 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Chinese Academy of Medical Sciences & Peking Union Medical College
state: Beijing
city: Beijing
country: China
facility: Plastic Surgery Hospital,Chinese Academy of Medical Sciences
state: Beijing
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Guangdong
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
state: Hebei
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University
state: Hebei
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Wuhan
country: China
facility: TongJi Hospital，TongJi Medical College Huazhong University of Science and Technology
state: Hubei
city: Shenyang
country: China
facility: The First Hospial of China Medical University
state: Liaoning
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer center
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital，Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: Hangzhou First People's Hospital
state: Zhejiang
city: Hanzhou
country: China
facility: Zhejiang Provincial People'S Hospital
state: Zhejiang
Study officials:
affiliation: Beijing Tiantan Hospital
name: Wenbin Li, MD
role: PRINCIPAL_INVESTIGATOR
References: