Neurofibromatosis 1, Plexiform Neurofibromas
Conditions
Brief summary
This is a Multi-center, Open-label, Single-arm Phase II Study to Evaluate the Efficacy and Safety of HL-085 in the treatment of Adult Participants with Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas(PN)
Detailed description
The study includes 2 parts, phase IIa and IIb. Phase IIa is to evaluate the preliminary safety, pharmacokinetic characteristics and efficacy of HL-085, and to determine the recommended dose. To observe the 9mg dose level, approximately 15 patients will receive HL-085 at a dose of 9mg BID on a continuous dosing schedule(1 cycle=21 days). The investigator and sponsor will evaluate the safety and efficacy data to determine whether HL-085 9mg BID is appropriate. HL-085 12mg BID, 6mg BID, or other HL-085 dosing regimen will be observed as needed. A total of 15-35 patients will be enrolled in phase IIa. Phase IIb is to further evaluate the safety and efficacy of HL-085 in patients with NF1 and inoperable PN and is expected to enroll 35 patients.
Interventions
DRUGHL-085
IIa: HL-085 capsule 9mg administered orally twice daily in a continuous 21-day treatment cycle. If required, dosing schedule can be adjusted to 12mg BID, 6mg BID, or other dosage regimens. IIb: HL-085 at the recommended dose or dosage regimen.
Sponsors
Shanghai Kechow Pharma, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age: patients must be ≥18 years of age at the time of study entry. * Diagnosis: Patients must have inoperable and symptomatic plexiform neurofibromas(PN), and patients must have NF1 mutation or meet at least 1 of the following NF1 diagnostic criteria: ① ≥6 cafe-au-lait macules ; ② Axillary freckling or freckling in inguinal regions; ③ ≥2 Lisch nodules (iris hamartomas); ④ A distinctive bony lesion such as dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex); ⑤ An optic pathway glioma; ⑥ First-degree relative with NF1. * Patients must have a measurable lesion, defined as at least 3 cm in length, amenable to MRI for efficacy assessment. * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. * Patients are able to understand and voluntarily sign a written informed consent form. * Patients must be willing and able to complete study procedures and follow-up examinations.
Exclusion criteria
* Patients who are unable to undergo MRI scans (prosthesis, prosthesis, braces, etc.) or patients with lesions that cannot be evaluated by MRI. * Patients do not have adequate organ function. * Patients who are unable to take drugs orally, have difficulty swallowing or anything that may lead to inadequate drug absorption. * Prior treatment with MEK 1/2 inhibitors. * Patients known to be allergic to the ingredients or analogues of the study drug. * Patients with previous or current retinal diseases such as retinal vein occlusion (RVO), retinal pigment epithelium detachment (RPED), central serous retinopathy (CSR), etc. (except retinopathy caused by research diseases). * With infections or other uncontrolled disease. * Strong CYP2C9 inhibitors or inducers within 7 days before treatment of the study drug. * Patients who received surgery within 4 weeks or radiotherapy within 6 weeks before enrollment. * Patients who participated in any other clinical study treatment within 4 weeks before enrollment. * Patients treated with anti-NF1 treatment with unresolved chronic toxicity. * Clinical judgment by the investigator that the patient should not participate in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | At the end of cycle 4,8,12,16,20,24,28,32.Then after every 8 cycles(each cycle is 21 days) | To assess the efficacy of HL-085 on the tumor volume (plexiform neurofibromas) using volumetric MRI per REiNS criteria. ORR is defined as the percentage of patients who have achieved a confirmed Partial Responses (PR) or Complete Responses (CR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate（DCR） | At the end of cycle 4,8,12,16,20,24,28,32.Then after every 8 cycles(each cycle is 21 days) | Defined as the percentage of patients who have achieved a confirmed response of CR or PR or SD |
| Duration of Overall Response（DOR） | At the end of cycle 4,8,12,16,20,24,28,32.Then after every 8 cycles(each cycle is 21 days) | Defined as the time from first achieved CR or PR to disease progression |
| Progression Free survival (PFS) | From date of dosing until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years | Defined as the time from first dosing (C1D1) to date of first observed progression or death from any cause (whichever comes first) |
| Pharmacokinetic characteristics | During the intervention | AUC |
Countries
China
Contacts
Primary ContactZhimei Zhu, Master
Backup ContactHongqi Tian, Ph.D
Outcome results
None listed