AzTrials
AzTrials

Advanced/ Metastatic Hepatocellular CarcinomaPhase 1/2NCT03499626

Phase 1b of ASLAN001 (Varlitinib) in Patients With Advanced/ Metastatic Hepatocellular Carcinoma (HCC)

A Phase 1/2 study testing ASLAN001 in people with Advanced/ Metastatic Hepatocellular Carcinoma, run by National University Hospital, Singapore at 1 site in Singapore.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 21 to 99 years
What is being tested?
ASLAN001
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
1 siteSingapore
Study dates
5 May 2017to 5 May 2021
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient must have unresectable or metastatic HCC with Childs Pugh status A with histologic confirmation.
  • 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.
  • 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 v1.1.
  • 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).
Show all 15Show fewer
  • Patients age ≥ 21 years at the time of written informed consent.
  • Patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • 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:
  • 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

Who cannot join

  • 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).
Show all 13Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Raghav Sundar contact

(65) 6779 5555

raghav_sundar@nuhs.edu.sg

Singapore1 site, 1 recruiting

  • National University Hospital

    Singapore, 119228

    Raghav Sundar, (65) 6779 5555, raghav_sundar@nuhs.edu.sg

    Recruiting

Other trials in Singapore

About this study

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

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

Read more

The secondary objectives include:

  1. 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)
  2. To assess the ORR, DoR, PFS, DCR and OS by tumor EGFR/HER2/HER3/HER4 status
  3. To identify tumor and host biomarkers predictive of treatment response or toxicity to ASLAN001.
Read the detailed description
  • 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.
Being tested
ASLAN001

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ASLAN001Drug

    Also called Varlitinib

    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

Study groups in NCT03499626
Study groupRoleWhat they receive
ASLAN001ExperimentalA 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.
Receives: Drug: ASLAN001

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Definition of MTD (maximum tolerable dose)

    The maximum tolerable dose is defined as the highest evaluated dose where < 1/6 patients experiences DLT during the DLT evaluation window.

    Measured: up to 1 year since the start of treatment

Secondary outcomes (2)

  1. Objective Response Rate

    Defined as the proportion of patients with a response of Partial Response or Complete Response, as defined by RECIST v1.1 criteria.

    Measurable disease:

    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

    Measured: up to 1 year since the start of treatment

  2. Progression Free Survival

    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.

    Measured: up to 1 year since the start of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Apr 2018
  2. Study start5 May 2017
  3. Primary completion5 May 2019 (estimated)
  4. Study completion5 May 2021 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03499626
Sponsor's protocol ID
2016/01227
Other IDs
HC01/12/16, 2016
Status last verified
Apr 2018
First submitted
8 Apr 2018
Last updated
17 Apr 2018
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Subbiah IM, Subbiah V, Tsimberidou AM, Naing A, Kaseb AO, Javle M, Fu S, Hong DS, Piha-Paul S, Wheler JJ, Hess KR, Janku F, Falchook GS, Wolff RA, Kurzrock R. Targeted therapy of advanced gallbladder cancer and cholangiocarcinoma with aggressive biology: eliciting early response signals from phase 1 trials. Oncotarget. 2013 Jan;4(1):156-65. doi: 10.18632/oncotarget.832.

    PubMed 23391555

  • Yang X, Wang W, Wang C, Wang L, Yang M, Qi M, Su H, Sun X, Liu Z, Zhang J, Qin X, Han B. Characterization of EGFR family gene aberrations in cholangiocarcinoma. Oncol Rep. 2014 Aug;32(2):700-8. doi: 10.3892/or.2014.3261. Epub 2014 Jun 13.

    PubMed 24927194

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ASLAN001 in people with Advanced/ Metastatic Hepatocellular Carcinoma, run by National University Hospital, Singapore at 1 site in Singapore.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 17 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Raghav Sundar ((65) 6779 5555, raghav_sundar@nuhs.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Definition of MTD (maximum tolerable dose) (time frame: up to 1 year since the start of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03499626, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2018.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in