Phase 1b of ASLAN001 (Varlitinib) in Patients With Advanced/ Metastatic Hepatocellular Carcinoma (HCC)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03499626|
Recruitment Status : Recruiting
First Posted : April 17, 2018
Last Update Posted : April 17, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Advanced/ Metastatic Hepatocellular Carcinoma||Drug: ASLAN001||Phase 1 Phase 2|
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||22 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||May 5, 2017|
|Estimated Primary Completion Date :||May 5, 2019|
|Estimated Study Completion Date :||May 5, 2021|
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.
Starting dose at 300mg BD Dose level +1: 400mg BD (which is the target dose for this study)
Dose reduction of ASLAN001 in event of adverse events grade 2 and above:
Dose level -1: 200mg BD Dose level -2: 100mg BD
Other Name: Varlitinib
- Definition of MTD (maximum tolerable dose) [ Time Frame: 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.
- Objective Response Rate [ Time Frame: up to 1 year since the start of treatment ]
Defined as the proportion of patients with a response of Partial Response or Complete Response, as defined by RECIST v1.1 criteria.
Tumor lesions: Must be accurately measured in at least one dimension (longest diameter in the plane of measurement is to be recorded) with a minimum size of 10mm on CT scan Malignant lymph node: ≥15mm in short axis on CT scan Non-measurable disease: All other lesions, including small lesions (longest diameter <10mm or pathological lymph nodes with >10 to <15mm short axis) as well as truly non-measurable lesions
- Progression Free Survival [ Time Frame: up to 1 year since the start of treatment ]Defined as the time from the start of treatment until the date of objective disease progression or death (by any cause in the absence of progression). Progression is defined in accordance with RECIST v1.1 criteria.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03499626
|Contact: Raghav Sundar||(65) 6779 email@example.com|
|National University Hospital||Recruiting|
|Singapore, Singapore, 119228|
|Contact: Raghav Sundar (65) 6779 5555 firstname.lastname@example.org|
|Principal Investigator:||Raghav Sundar||National University Hospital, Singapore|