ASLAN001 in Patients With Advanced or Metastatic Cholangiocarcinoma Who Progressed on at Least 1 Line of Systemic Therapy

NCT02609958 | Completed Phase 2

• 1 other identifier: ASLAN001-005
• Study Type: interventional
• Target: 32
• Locations: 3 countries
• Sites: 3

Brief Summary

This is a single arm, multicentre, Phase 2 study to assess efficacy and safety of ASLAN001 in patients with advanced or metastatic cholangiocarcinoma who progressed on at least 1 line of systemic therapy. 25 evaluable patients will be enrolled in the study. After evaluation of initial response in the first 10 evaluable patients, Sponsor will make a decision on recruitment of an additional 15 evaluable patients. If no response is observed, the study will stop. The primary objective is to assess efficacy of varlitinib (also known as ASLAN001) as measured by ORR (based on RECIST v1.1). The secondary objectives are to (1) evaluate the efficacy of varlitinib, as measured by DoR, PFS, OS and DCR, (2) assess ORR, DoR, PFS, DCR and OS by tumor EGFR/HER2 status, (3) assess safety and tolerability of ASLAN001 monotherapy. Exploratory objectives are to explore possible relationships between response to ASLAN001 and the protein expression levels and gene mutational status of the proteins and genes via IHC and PCR/Sequencing.

Conditions

Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Defined as the proportion of patients with a response of PR or CR, as defined by RECIST v1.1 criteria. Data obtained up until disease progression, or last evaluable assessment in the absence of disease progression, will be included in the assessment of ORR.

  Through study duration, estimated 3 years

Secondary Outcomes (5)

• Progression Free Survival (PFS)

  Through study duration, estimated 3 years

• Disease Control Rate (DCR)

  Through study duration, estimated 3 years

• Duration of Response (DoR)

  Through study duration, estimated 3 years

• Overall Survival (OS)

  Through study duration, estimated 3 years

• Safety for all advanced or metastatic Cholangiocarcinoma (CCA) subjects (Physical examination, vital signs, weight, ECG parameter, clinical laboratory tests and Adverse Events)

  Through study duration, estimated 3 years

Other Outcomes (1)

• Possible relationship of protein expression level and gene mutational status determined from archival material or biopsy tissue samples with response to ASLAN001.

  Through study duration, estimated 3 years

Study Arms (1)

Treatment Arm A

EXPERIMENTAL

Varlitinib (ASLAN001) tablets

Drug: Varlitinib

Interventions

Varlitinib DRUG

varlitinib tablets with: 1. starting dose: 300mg BID 2. target dose: 400mg BID 3. dose modification by investigator allowed between 200mg BID to 500mg BID

Also known as: ASLAN001, ARRY-334543, ARRY-543

Treatment Arm A

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must have advanced (unresectable) or metastatic, intra or extra hepatic adenocarcinoma originated from bile duct. Histologically-confirmed diagnosis is required for the first 10 evaluable patients. The following patients could be confirmed histologically or cytologically.
• Patients must have disease progression after failing at least 1 line of systemic drug regimen for advanced cholangiocarcinoma 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 of respective country's legal age or older at the time of written informed consent.
• Patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Patient must be able to understand and willing to sign the informed consent form and donate tumour tissue (archival or fresh) for evaluation of relevant exploratory endpoints. The first 10 evaluable patients need to have adequate archival tissues for exploratory objectives.
• Patient with adequate organ and hematological function:
• Hematological function, as follows:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L
• Platelet count ≥ 100 x 10\^9/L
• Renal functions, as follows:
• Serum creatinine ≤ 1.5x ULN or eGFR \> 60 mL/min/1.73m\^2
• Hepatic function, as follows:
• Total bilirubin ≤ 1.5 x ULN

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 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 hepatitis B with HBV DNA \> 2000 IU/ml or persistent abnormal ALT in the past 6 months, chronic hepatitis C with persistent abnormal ALT in the past 6 months.
• Known History of drug addiction within last 1 year.
• 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.
• For additional information regarding investigative sites for this trial, pls contact ASLAN at contactus@aslanpharma.com

Sponsors & Collaborators

• ASLAN Pharmaceuticals: lead

Study Sites (3)

Unknown Facility

Singapore, Singapore

Location

Unknown Facility

Seoul, South Korea

Location

Unknown Facility

Taipei, Taiwan

Location

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

ARRY-334543

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Please contact us for more information

  ASLAN Pharmaceuticals Pte Ltd

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2015
• First Posted: November 20, 2015
• Study Start: November 16, 2015
• Primary Completion: July 7, 2017
• Study Completion: October 11, 2017
• Last Updated: May 29, 2018

Record last verified: 2018-05

Locations

KR (1); TW (1); SG (1)