NCT03499626Unknown1 期
Phase 1b Open Label Dose Assessment Study of ASLAN001 (Varlitinib) in Patients With Advanced/ Metastatic Hepatocellular Carcinoma (HCC) With an Expansion Cohort in HCC Patients Expressing HER3 Who Have Progressed on First Line Sorafenib or Lenvatinib
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Definition of MTD (maximum tolerable dose)
研究概览
简要总结
This is a single-arm, allocation open label study. Phase 1 is a dose-finding phase in patients with advanced/ metastatic hepatocellular carcinoma (HCC) who have progressed on first line Sorafenib or Lenvatinib.
The primary objective of this study will be to establish the maximal tolerable dose (MTD) of ASLAN001 (Varlitinib) in the study population
The secondary objectives include:
- To evaluate the efficacy of ASLAN001 (Varlitinib), as measured by duration of response (DoR), progression free survival (PFS), overall survival (OS) and disease control rate (DCR)
- To assess the ORR, DoR, PFS, DCR and OS by tumor EGFR/HER2/HER3/HER4 status
- To identify tumor and host biomarkers predictive of treatment response or toxicity to ASLAN001.
详细描述
- There are currently no effective and approved second line treatment options for advanced/ metastatic HCC.
- ASLAN001 (Varlitinib) is a small molecule tyrosine kinase inhibitor against HER1 (EGFR), HER2, and HER4.
- In vivo studies on HER2/3 expressing HCC PDX models suggest inhibition of pERB B2/3, pERK1 and pERK 2 with treatment with ASLAN001 (Varlitinib). Dose dependent inhibition of Cdc2 and pAKT in HCC PDX models treated with ASLAN001 (Varlitinib) also suggest robust inhibition of the PI3K pathway.
- EGFR overexpression in HCC and matched non tumor tissues were detected in (32.5%) and (28.6%), respectively. Moreover, missense and silent mutations were detected in (39.4%) and (33.3%) of HCC tissues, respectively.
- Determine the maximum tolerable dose (MTD) of ASLAN001 (Varlitinib) in advanced/metastatic HCC patients.
- After the recommended dose is determined, the Phase Ib portion of the study will evaluate the efficacy of ASLAN001 (Varlitinib) in HCC patients who have progressed on Sorafenib.
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
- 21 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient must have unresectable or metastatic HCC with Childs Pugh status A with histologic confirmation.
- •i) Subjects with only a radiologic diagnosis of HCC may be enrolled for screening in the study but histological confirmation is mandatory prior to the start of study therapy.
- •ii) Evaluable tumor tissue (formalin-fixed, paraffin embedded archival or recent acquisition) must have 15 unstained slides for correlative studies. If archived samples are not available, subjects must consent to a pre-treatment fresh biopsy as a condition of protocol participation.
- •Patients must have failed Sorafenib or Lenvatinib due to disease progression or intolerance.
- •Presence of radiographically measurable disease based on RECIST v1.
- •No evidence of biliary duct obstruction, unless obstruction is controlled by local treatment or, in whom the biliary tree can be decompressed by endoscopic or percutaneous stenting with subsequent reduction in bilirubin to below 1.5 x upper level of normal (ULN).
- •Patients age ≥ 21 years at the time of written informed consent.
- •Patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Patient must be able to understand and willing to sign the informed consent form and donate tumor tissue (archival or fresh) for evaluation of relevant exploratory endpoints.
- •Patient with adequate organ and hematological function:
- •a. Hematological function, as follows: i. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L ii. Platelet count ≥ 80 x 10^9/L b. Renal functions, as follows: i. Serum creatinine ≤ 1.5x ULN or eGFR > 60 mL/min/1.73m2 c. Hepatic function in addition to Childs Pugh score A: i. Total bilirubin ≤ 1.5 x ULN ii. AST and ALT ≤ 2.5 x ULN
- •Expansion cohort
- •Patients must agree to a post treatment biopsy
- •HER3 expression on IHC
- •Other inclusion criteria as above
排除标准
- •Patient with radiation or local treatment within the past 6 weeks for the target lesion(s).
- •Patients with major surgical procedures within 21 days prior to study entry.
- •Patient with brain lesion, known brain metastases (unless previously treated and well controlled for a period of at least 3 months).
- •Patient with malabsorption syndrome, diseases significantly affecting gastrointestinal function, resection of the stomach or small bowel, or difficulty in swallowing and retaining oral medications.
- •Patients with an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, cardiac arrhythmia, diabetes, hypertension, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Patients with any history of other malignancy unless in remission for more than 1 year. (Non-melanoma skin carcinoma and carcinoma-in-site of uterine cervix treated with curative intent is not exclusionary).
- •Female patients who are pregnant or breast feeding.
- •Patients who were previously treated with ASLAN001 (Varlitinib).
- •Patients who have received any investigational drug (or have used an investigational device) within the last 14 days before receiving the first dose of study medication.
- •Patient with unresolved or unstable serious toxicity ( ≥ CTCAE 4.03 Grade 2) from prior administration of another investigational drug and/or prior cancer treatment.
- •Patients with a known history of HIV, decompensated cirrhosis, chronic active hepatitis or chronic persistent hepatitis.
- •Patients who need continuous treatment with proton pump inhibitors during the study period.
- •Any history or presence of clinically significant cardiovascular, respiratory, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic or psychiatric disease or any other condition which in the opinion of the Investigator could jeopardize the safety of the patient or the validity of the study results
研究组 & 干预措施
ASLAN001
Experimental
A 3+3 study de-escalating dose design will be employed for dose determination. Subjects will receive treatment in 21-day cycles until disease progression, intolerable toxicities or withdrawal of consent.
干预措施: ASLAN001 (Drug)
结局指标
主要结局
Definition of MTD (maximum tolerable dose)
时间窗: up to 1 year since the start of treatment
The maximum tolerable dose is defined as the highest evaluated dose where \< 1/6 patients experiences DLT during the DLT evaluation window.
次要结局
- Objective Response Rate(up to 1 year since the start of treatment)
- Progression Free Survival(up to 1 year since the start of treatment)
研究者
研究点 (1)
Loading locations...
相似试验
终止
1 期
P-BCMA-101 Tscm CAR-T Cells in the Treatment of Patients With Multiple Myeloma (MM)Multiple MyelomaNCT03288493Poseida Therapeutics, Inc.105
已完成
1 期
A Study of ASN007 in Patients With Advanced Solid TumorsMalignancyNeoplasiaCancerNeoplasm MetastasisColonic NeoplasmsColon Cancer Liver MetastasisMetastatic CancerMetastatic MelanomaMetastatic Lung CancerNon Small Cell Lung Cancer MetastaticPancreas CancerPancreas AdenocarcinomaPancreas NeoplasmMetastatic Nonsmall Cell Lung CancerMetastatic Pancreatic CancerPancreatic CancerColon CancerNeoplasmMetastatic Colon CancerNCT03415126Asana BioSciences49
Unknown
1 期
Study of Welgenaleucel (UWC19) in Patients With Relapsed or Refractory B-cell LymphomaB-cell Non-Hodgkin LymphomaNCT04296461UWELL Biopharma20
已完成
2 期
A Study to Evaluate the Efficacy and Safety of CBL-514 in Participants With EFP; Cellulite (Stage 1)CelluliteNCT05632926Caliway Biopharmaceuticals Co., Ltd.12
已完成
1 期
A Trial of SHR2285 in Healthy SubjectsHealthy VolunteersNCT04829305Atridia Pty Ltd.31