FCN-159 Monotherapy Versus Chemotherapy by Investigator's Choice in Pediatric Low-grade Glioma Patients With BRAF Alteration

Official title

An Open-label, Randomized, Multi-center Phase III Clinical Study: Aim to Evaluate the Efficacy and Safety of FCN-159 Monotherapy Versus the Treatment by Investigator's Choice in Patients With Pediatric Low-grade Glioma Harboring KIAA1549-BRAF Fusion or BRAF V600E Mutation

Overview

An open-label, randomized, multi-center phase III clinical study: Aim to evaluate the efficacy and safety of FCN-159 monotherapy versus the treatment by investigator's choice in patients with pediatric low-grade glioma harboring KIAA1549-BRAF fusion or BRAF V600E mutation

Interventions

• Drug Luvometinib
  Luvometinib oral tablet
• Biological Chemotherapeutic Agent COG-V/C Carboplatin + Vindesine, Carboplatin, Temozolomide
  Investigator's choice of chemotherapy administered IV or orally

Primary outcome measures

• Compare the progression free survival (PFS) of FCN-159 versus chemotherapy by IRC [Time frame: up to 48 months]

Secondary outcome measures (7)

• PFS of FCN-159 versus chemotherapy by INV [Time frame: up to 48 months]
• Objective response rate (ORR) of FCN-159 versus chemotherapy [Time frame: up to 48 months]
• Clinical benefit rate (CBR) of FCN-159 versus chemotherapy [Time frame: up to 48 months]
• Duration of overall response (DOR) of FCN-159 versus chemotherapy [Time frame: up to 48 months]
• Time to response (TTR) of FCN-159 versus chemotherapy [Time frame: up to 48 months]
• Overall survival (OS) of FCN-159 vesus chemotherapy [Time frame: up to 48 months]
• Safety of FCN-159 versus chemotherapy [Time frame: up to 48 months]

Eligibility criteria

Inclusion criteria

• Pediatric patients aged between ≥ 2 years and < 18 years; regardless of male or female.
• Histologically and/or cytologically confirmed diagnosis of low-grade glioma (pLGG diagnosis as Grade 1 or 2 according to the 2021 WHO classification of CNS).
• KIAA1549-BRAF fusion or BRAF V600E mutation-positive.
• Patients requiring systemic therapy as determined by the investigator, including patients having disease recurrence or progression, or residual disease of surgery, or unresectable.
• At least one intracranial measurable lesion that can be reproducibly measured in two dimensions on T2-FLAIR, with the minimum size of the bi-perpendicular diameter of ≥ 10 mm, and can be visible on two or more imaging slice.

6\. Karnofsky performance score or Lansky performance score ≥ 70. 7．Adequate organ function within 14 days before enrollment.

Exclusion criteria

• Patients who have previously received any of the following treatments:

• Patients who have received chemotherapy drugs or traditional Chinese medicines or herbals with definitive anti-tumor treatment within 4 weeks preceding the first dose of investigational drug;
• Patients who have received growth factors that promote platelet or leukocyte count or function within 14 days preceding the first dose of investigational drug;
• Patients who received radiotherapy, surgery or immunotherapy within 4 weeks preceding the first dose of investigational drug;
• Patients who have participated in other interventional clinical trials within 4 weeks before receiving the first dose of investigational drug;
• Patients who have received live vaccines within 4 weeks preceding the first dose of investigational drug, or patients who have received inactivated vaccines and mRNA vaccines within 14 days preceding the study treatment;
• Patients who have previously received any other MEK 1/2 inhibitors such as Selumetinib or BRAF inhibitors such as Dabrafenib.
• Patients with high-grade gliomas, as well as schwannoma, subependymal giant cell astrocytoma (tuberous sclerosis), and diffuse intrinsic pontine gliomas (even if the histological diagnosis is WHO Grade 1 or 2).
• Patients who require endotracheal intubation for assisted ventilation or tracheotomy should be excluded.
• Patients who have uncontrollable epilepsy as assessed by the investigator.
• Patients with dysphagia, active GI diseases, malabsorption syndrome, or other conditions that will interfere with the absorption of the investigational drug.
• Patients with clinically significant active bacterial, fungal or viral infections, including hepatitis B virus surface antigen positive and hepatitis B virus DNA exceeding 1000 IU/ml. Hepatitis B carriers are allowed to be enrolled. Patients with positive hepatitis C virus (HCV) antibody test; those who have confirmed human immunodeficiency virus (HIV) infection, and are unwilling to undergo HIV testing.
• Patients with history or current evidence of retinal vein obstruction (RVO), retinal pigment epithelial detachment (RPED), central retinal vein occlusion, glaucoma, and other significant abnormalities in ophthalmological examinations.
• Interstitial pneumonia, including clinically significant radiation pneumonitis.
• Grade 3 creatine phosphokinase increased (>5 × ULN - 10 × ULN).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Beijing Tiantan Hospital, Capital Medical University — Beijing

Identifiers

NCT: NCT07004075 · FCN-159-010

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗