- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03129074
Study of Varlitinib Plus Capecitabine in Patients With Advanced or Metastatic Biliary Tract Cancer
May 21, 2018 updated by: ASLAN Pharmaceuticals
A Phase 2, Single Arm Study of Varlitinib Plus Capecitabine in Patients With Advanced or Metastatic Biliary Tract Cancer as First-line Systemic Therapy
The purpose of the study is to assess the efficacy of varlitinib in combination with capecitabine as measured by objective response rate (ORR) assessed by independent central review (ICR), based on RECIST v1.1 criteria.
Study Overview
Status
Withdrawn
Conditions
Intervention / Treatment
Detailed Description
Also to explore the role of biomarkers as predictors of response and clinical benefit with varlitinib
Study Type
Interventional
Phase
- Phase 2
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Are of or older than the legal age in the respective countries at the time when written informed consent is obtained.
- Are able to understand and willing to sign the informed consent form.
- Have histologically confirmed diagnoses of relapsed, locally advanced (unresectable) or metastatic biliary tract cancer, including intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer and carcinoma of Ampulla of Vater.
Have eligible tumor tissue (archival or fresh) for the evaluation of relevant primary endpoints.
(Note: For patients without eligible tumor tissue, a discussion with the sponsor is mandatory).
- Have radiographically measurable disease as determined by the investigator based on the RECIST v1.1 criteria.
- Have 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).
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Have an estimated life expectancy of more than 3 months, at the time of screening.
Have adequate organ and hematological function:
Hematological function, as follows:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelet count ≥ 100 x 109/L
Renal functions, as follows:
- estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl) > 50 mL/min/1.73m2
Hepatic function, as follows:
- Total bilirubin ≤ 1.5 x ULN
- aspartate aminotransferase and alanine aminotransferase ≤ 5 x ULN
Exclusion Criteria:
- Have received systemic anti-cancer treatment except (neo-) adjuvant therapy for early stage disease.
- Are currently on or have received radiation or local treatment within the past 4 weeks for the target lesion(s), prior to screening.
- Had undergone major surgical procedures within 28 days prior to study cycle 1 day 1.
- Have a metastatic brain lesion(s), including asymptomatic and well controlled lesion(s).
- Have malabsorption syndrome, diseases significantly affecting gastrointestinal function, or difficulty in swallowing and retaining oral medications.
- Have any history of other malignancy unless in remission for more than 1 year (skin carcinoma and carcinoma-in-site of uterine cervix treated with curative intent is not exclusionary).
- Are female patients who are pregnant or breast feeding.
- Have been previously treated with varlitinib or capecitabine.
- Have received any investigational drug (or have used an investigational device) within the last 14 days before receiving the first dose of study medication.
- Have unresolved or unstable serious toxicity (≥ CTCAE 4.03 Grade 2), with the exception of anemia, asthenia, and alopecia, from prior administration of another investigational drug and/or prior anti-cancer treatment.
- Have a known positive test for human immunodeficiency virus, active viral hepatitis C, viral hepatitis B infection with hepatitis B virus DNA exceeding 2000 IU/mL.
- Have a known history of drug addiction within last 1 year, on the basis of which there could be a higher risk of non-compliance to study treatment.
- Need continuous treatment with proton pump inhibitors during the study period.
- Have a history of (non-infectious) pneumonitis that required steroids or current pneumonitis, or with a history of interstitial lung disease or current interstitial lung disease.
- Have any history or presence of clinically significant condition which in the opinion of the investigator could jeopardize the safety of the patient or the validity of the study results.
- Have a baseline corrected QT interval > 450 ms or patients with known long QT syndrome, torsade de pointes, symptomatic ventricular tachycardia, unstable cardiac syndrome in the past 3 months before screening visit, > class 2 NYHA (The New York Heart Association Functional Classification heart failure), > grade 2 CCS (the Canadian Cardiovascular Society Guidelines) angina pectoris, or receiving quinidine, procainamide, disopyramide, amiodarone, dronedarone, arsenic, dofetilide, or sotalol methadone.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Varlitinib given in combination with capecitabine
|
everyday
from Day 1 to Day 14 followed by 7-day of rest period, every 21 days.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate (ORR)
Time Frame: Through study duration, estimated 3 years
|
Number (%) of patients with at least one visit response of CR or PR.
Tumor evaluations will continue until the earlier of disease progression or starting a subsequent anti-cancer therapy.
|
Through study duration, estimated 3 years
|
Biomarker
Time Frame: Through study duration, estimated 3 years
|
Use Next generation sequencing/Immunohistochemistry to identify relationships between response to varlitinib and mutations or overexpression in human epidermal growth factor receptor (HER) receptors and the downstream signaling proteins, as well as, mutations in selected cancer pathways.
|
Through study duration, estimated 3 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free survival (PFS)
Time Frame: Through study duration, estimated 3 years
|
Defined as the time from start of treatment until the date of objective disease progression or death (by any cause in the absence of disease progression).
|
Through study duration, estimated 3 years
|
Overall survival (OS)
Time Frame: Through study duration, estimated 3 years
|
Defined as the time from start of treatment until death by any cause.
|
Through study duration, estimated 3 years
|
Duration of response (DoR)
Time Frame: Through study duration, estimated 3 years
|
Defined as the time, in days, from the first recorded achievement of a response (PR or above) until time of objective disease progression in the subset of patients classified as responders in the assessment of ORR
|
Through study duration, estimated 3 years
|
Disease control rate (DCR)
Time Frame: Through study duration, estimated 3 years
|
Defined as the proportion of patients with a best response of stable disease maintained for at least 12 weeks (-5 days), PR or CR as defined by RECIST v1.1 criteria.
|
Through study duration, estimated 3 years
|
Objective response rate (ORR)
Time Frame: Through study duration, estimated 3 years
|
Defined as the proportion of patients with a best objective response (BOR) of complete response (CR) or partial response (PR), as assessed by the investigator defined by the RECIST v1.1 criteria.
|
Through study duration, estimated 3 years
|
Incidence of Adverse Events and changes from baseline in safety parameters
Time Frame: Through study duration, estimated 3 years
|
Incidence of Adverse Events, categorized in accordance to CTCAE 4.03 and changes from baseline in safety parameters (including vital signs, ECG parameters, clinical laboratory tests).
|
Through study duration, estimated 3 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Anticipated)
May 1, 2018
Primary Completion (Anticipated)
March 1, 2020
Study Completion (Anticipated)
September 1, 2020
Study Registration Dates
First Submitted
April 21, 2017
First Submitted That Met QC Criteria
April 25, 2017
First Posted (Actual)
April 26, 2017
Study Record Updates
Last Update Posted (Actual)
May 23, 2018
Last Update Submitted That Met QC Criteria
May 21, 2018
Last Verified
May 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ASLAN001-016
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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