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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
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)
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 NF
- •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-
- •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.
排除标准
- •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.
研究组 & 干预措施
HL-085
HL-085 9mg BID
干预措施: HL-085 (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: 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).
次要结局
- 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))
- 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))
- Pharmacokinetic characteristics(During the intervention)
- 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)