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

NCT03499626 | Unknown Phase 1

• 2 other identifiers: 2016/01227HC01/12/16
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief 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. 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:

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

Conditions

Advanced/ Metastatic Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (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.

  up to 1 year since the start of treatment

Secondary Outcomes (2)

• Objective Response Rate

  up to 1 year since the start of treatment

• Progression Free Survival

  up to 1 year since the start of treatment

Study Arms (1)

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.

Drug: ASLAN001

Interventions

ASLAN001 DRUG

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

Also known as: Varlitinib

ASLAN001

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 v1.1.
• 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).
• 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:
• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

National University Hospital

Singapore, 119228, Singapore

RECRUITING

Related Publications (2)

• 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.

  PMID: 23391555 BACKGROUND

• 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.

  PMID: 24927194 BACKGROUND

Study Officials

• Raghav Sundar

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Raghav Sundar

CONTACT

(65) 6779 5555; raghav_sundar@nuhs.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2018
• First Posted: April 17, 2018
• Study Start: May 5, 2017
• Primary Completion: May 5, 2019
• Study Completion: May 5, 2021
• Last Updated: April 17, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)