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Biliary Tract CancerPhase 2/3TreeToppNCT03093870

Varlitinib in Combination With Capecitabine for Advanced or Metastatic Biliary Tract Cancer

A Phase 2/3 study testing Varlitinib and Capecitabine in people with Biliary Tract Cancer, run by ASLAN Pharmaceuticals at 21 sites in 11 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This protocol for Varlitinib is developed for the treatment of Biliary Tract Cancer. Varlitinib (also known as ASLAN001) is a small-molecule, adenosine triphosphate competitive inhibitor of the tyrosine kinases - epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER)2, and HER4. Read more about this study

Who is it for?
Any age
Conditions the study is for
Biliary Tract Cancer
What is being tested?
Varlitinib and Capecitabine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
151 participants
Where
21 sitesin 11 countries
Study dates
4 Jul 2017to 17 Apr 2020
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Subjects will be eligible for the study if they:
  • Are of or older than the legal age in the respective countries at the time when written informed consent is obtained
  • Have histologically or cytologically confirmed advanced (unresectable) or metastatic biliary tract cancer, including intrahepatic or extrahepatic cholangiocarcinoma (CCA), gallbladder cancer and carcinoma of Ampulla of Vater. This includes clinical diagnosis of biliary tract cancer with histological confirmation of adenocarcinoma.
  • Have received and failed one and only one prior line of systemic treatment for advanced or metastatic disease with radiologic evidence of disease progression. This prior line of systemic treatment must also contain gemcitabine
  • Have received at least 6 doses of gemcitabine containing treatment in first line (Adjuvant therapy is not regarded as 1st line therapy)
  • Have radiographically measurable disease based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 as assessed by Independent Central Review (ICR) (For Part 1)
Show all 19Show fewer
  • 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 or equal to 1.5 × upper level of normal (ULN)
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Are able to understand and willing to sign the informed consent form
  • Have adequate organ and hematological function:
  • Hematological function, as follows:
  • Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
  • Platelet count ≥ 100 × 109/L
  • Renal functions, as follows:
  • Estimated glomerular filtration rate or creatinine clearance > 50 mL/min/1.73m2
  • Hepatic function, as follows:
  • Albumin ≥ 3 g/dL
  • Total bilirubin ≤ 1.5 × ULN
  • Aspartate aminotransferase and alanine aminotransferase ≤ 5 × ULN

Who cannot join

  • Subjects will be ineligible for the study if they:
  • Are currently on or have received anti-cancer therapy within the past 3 weeks before receiving the first dose of study medication
  • Are currently on or have received radiation or local treatment within the past 3 weeks for the target lesion(s) before receiving the first dose of study medication
  • Have evidence of multiple (≥ 2) peritoneal metastases or ascites at baseline as assessed by ICR (For Part 1). (Ascites which can be attributed by non-malignant causes is not excluded. Minimal ascites, which does not require paracentesis is permitted.)
  • Have had major surgical procedures within 14 days prior to first dose of study medication
  • Have a known metastatic brain lesion(s), including asymptomatic and well controlled lesion(s)
Show all 19Show fewer
  • Have malabsorption syndrome, diseases significantly affecting gastrointestinal function, resection of the stomach or small bowel, or difficulty in swallowing and retaining oral medications which in the opinion of the Investigator could jeopardize the validity of the study results
  • Have 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
  • Have 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)
  • Are female patients who are pregnant or breast feeding
  • Have been previously treated with varlitinib or have been previously treated with capecitabine as first line therapy for advanced or metastatic disease. For patients who have previously received capecitabine as a radiosensitizer or as part of their adjuvant therapy and their disease has relapsed for more than 6 months after their last dose of capecitabine adjuvant therapy, their capecitabine therapy will not be considered as a line of systemic chemotherapy for metastatic/advanced disease, and thus they can participate in the study
  • 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 (≥ common terminology criteria for adverse events [CTCAE] 4.03 Grade 2), with the exception of anemia, asthenia, and alopecia, from prior administration of another investigational drug and/or prior cancer treatment
  • Have a known positive test for human immunodeficiency virus, hepatitis C (treatment naïve or after treatment without sustained virologic response), or hepatitis B infection with hepatitis B virus deoxyribonucleic acid exceeding 2000 IU/mL
  • Have a known history of drug addiction within last 1 year which, in the opinion of the Investigator, could increase the risk of non-compliance to investigational product
  • 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 have a history of interstitial lung disease or current interstitial lung disease
  • Have 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
  • Have a baseline corrected QT interval (Fridericia's formula) (QTcF) > 450 ms or patients with known long QT syndrome; torsade de pointes; symptomatic ventricular tachycardia; an unstable cardiac syndrome in the past 3 months before screening visit; > class 2 New York Heart Association heart failure; or > class 2 angina pectoris; or receiving quinidine, procainamide, disopyramide, amiodarone, dronedarone, arsenic, dofetilide, sotalol, or methadone. Please also see prohibited medication/therapy (Section 5.4.10.1)

Trial locations and contacts

21 sites in 11 countries.

21 sites in 11 countries

United States11 sites
  • Levine Cancer Institute, Carolinas Healthcare System

    Charlotte, North Carolina, 28204

  • Texas Oncology, P.A.

    Dallas, Texas, 12221

  • Karmanos Cancer Institute/Wayne State University

    Detroit, Michigan, 48201

  • Duke University Medical Center

    Durham, North Carolina, 27705

  • Banner MD Anderson Cancer Center

    Gilbert, Arizona, 85234

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

  • CCCN

    Las Vegas, Nevada, 89169

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Ruttenberg Cancer Center, Mount Sinai Hospital

    New York, New York, 10029

  • UPMC Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

Australia1 site
  • There are 5 sites in different cities in Australia

    Camperdown

Other trials in Australia

China1 site
  • There are 6 sites in different cities in China

    Nanjing, Nanjing, 210031

Other trials in China

Hong Kong1 site
  • There are 2 sites in Hong Kong

    Hong Kong

Other trials in Hong Kong

Hungary1 site
  • There are 2 sites in Hungary

    Budapest, 1062

Other trials in Hungary

Japan1 site
  • There are 7 sites in different cities in Japan

    Chiba

Other trials in Japan

Poland1 site
  • There are 2 sites in different cities in Poland

    Otwock, 05-400

Other trials in Poland

Singapore1 site
  • There are 2 sites in Singapore.

    Singapore, 169610

Other trials in Singapore

South Korea1 site
  • There are 15 sites in different cities in South Korea

    Seoul

Other trials in South Korea

Spain1 site
  • There are 5 sites in different cities in Spain

    Barcelona, 08035

Other trials in Spain

Taiwan1 site
  • There are 5 sites in different cities in Taiwan

    Taipei, 11217

Other trials in Taiwan

About this study

Official title: A Multicenter, Double-Blind, Randomized, Placebo-Controlled Study of Varlitinib Plus Capecitabine Versus Placebo Plus Capecitabine in Patients With Advanced or Metastatic Biliary Tract Cancer as Second Line Systemic Therapy

This protocol for Varlitinib is developed for the treatment of Biliary Tract Cancer. Varlitinib (also known as ASLAN001) is a small-molecule, adenosine triphosphate competitive inhibitor of the tyrosine kinases - epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER)2, and HER4. Varlitinib may be beneficial to subjects with cancer by simultaneous inhibition of these receptors. The purpose of this study is to determine the safety and efficacy of Varlitinib in combination with capecitabine for the treatment of Biliary Tract Cancer. Treatment groups are Varlitinib+capecitabine and Placebo + capecitabine

Read the detailed description

Part 1 of study(Phase 2) is planned to have 120 patients and anticipated completion on July 2019. Recruitment completed.

Part 2 of study(Phase 3) is planned to have 350 patients and anticipated completion on Dec 2022. Not yet recruiting.

Being tested
Varlitinib, Capecitabine, Placebo (for Varlitinib)
Keywords
Neoplasms, Biliary Tract Neoplasms, Bile Duct Neoplasms, Gallbladder Neoplasms
Medical subject headings
Biliary Tract Neoplasms, Neoplasms, Bile Duct Neoplasms, Gallbladder Neoplasms

What participants receive

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

  • VarlitinibDrug

    Also called ASLAN001, ARRY-334543, QBT01

    Varlitinib:300mg, oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

  • CapecitabineDrug

    1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

  • Placebo (for Varlitinib)Drug

    oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death

Study groups in NCT03093870
Study groupRoleWhat they receive
Varlitinib and CapecitabineExperimentalNot described
Receives: Drug: Varlitinib; Drug: Capecitabine
Placebo and CapecitabinePlacebo comparatorNot described
Receives: Drug: Capecitabine; Drug: Placebo (for Varlitinib)

What is being measured

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

  1. Objective Response Rate (ORR) - Part 1

    Part 1: The ORR was defined as the number (%) of subjects with ≥ 1 visit response of complete response (CR) or partial response (PR). Data obtained up until progression, or until last evaluable assessment in the absence of progression, was included in the assessment of ORR, regardless of whether subjects discontinued treatment or received a subsequent therapy prior to progression. Best overall RECIST Response (BOR) was calculated based on the overall visit responses from each RECIST assessment, i.e. the best response a subject had following randomization and prior to RECIST progression or the last evaluable assessment in the absence of RECIST progression. Categorization of BOR was based on the RECIST criteria using the following response categories: CR, PR, stable disease (SD), progressive disease (PD) and not evaluable (NE).

    Measured: Data obtained up until progression, or until last evaluable assessment in the absence of progression, regardless of whether subjects discontinued treatment or received a subsequent therapy prior to progression, up to 2 years.

  2. Progression-free Survival (PFS) - Part 1

    Part 1: Progression-free survival (PFS) was defined as the time from randomization (or starting treatment for the Safety Lead-in) until the date of objective disease progression or death (by any cause in the absence of disease progression) regardless of whether the subject withdrew from randomized therapy or received another antitumor therapy prior to disease progression. Subjects who did not experience disease progression or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment. However, if the patient progressed or died after ≥ 2 missed visits (12 weeks ± 5 days maximum), the subject was censored at the time of the latest evaluable RECIST assessment. The PFS time was based on the scan/assessment dates rather than visit dates.

    Measured: Time from randomization until date of objective disease progression or death (by any cause in absence of disease progression) regardless of whether subject withdrew from randomized therapy or received another antitumor therapy prior to PD, up to 2 years.

Secondary outcomes (13)
  1. Object Response Rates (ORR) - Safety Lead-In

    The ORR rate was defined as the number (%) of subjects with ≥ 1 visit response of complete response (CR) or partial response (PR). Data obtained up until progression, or until last evaluable assessment in the absence of progression, was included in the assessment of ORR, regardless of whether subjects discontinued treatment or received a subsequent therapy prior to progression. In all study parts, the primary assessment of ORR was based on the Full Analysis Set (FAS).

    Measured: Data obtained up until progression, or until last evaluable assessment in absence of progression, regardless of whether subjects discontinued treatment or received a subsequent therapy prior to progression, up to 2 years.

  2. Overall Survival (OS) - Part 1

    Part 1: Overall survival (OS) was defined as the time from the date of randomization until death due to any cause. Any subject not known to have died at the time of the data cut-off was censored based on the last recorded date on which the subject was known to be alive.

    Measured: Time from the date of randomization until death due to any cause, up to 2 years

  3. Overall Survival (OS) - Safety Lead-In

    Part 1: Overall survival (OS) was defined as the time from the date of randomization until death due to any cause. Any subject not known to have died at the time of the data cut-off was censored based on the last recorded date on which the subject was known to be alive.

    Measured: Time from the date of randomization until death due to any cause, up to 2 years

  4. Duration of Response (DoR) - Part 1

    Part 1: Duration of response (DoR) was defined as the time from the date of first documented response until the date of documented PD or death in the absence of disease progression. The end of the response should have coincided with the date of disease progression or death from any cause used for the PFS endpoint.

    For Part 1, DoR was calculated based on data from the ICR of radiological data.

    Measured: Time from the date of first documented response until the date of documented PD or death in the absence of disease progression, up to 2 years

  5. Disease Control Rate DCR - Part 1

    Part 1: DCR rate was defined as the number (%) of subjects with ≥ 1 visit response of CR or PR, or with SD for a minimum of 12 weeks (± 5 days) from randomization. Data obtained up until progression, or until last evaluable assessment in the absence of progression, were included in the assessment of DCR, regardless of whether subjects discontinued treatment or received a subsequent therapy prior to progression. For all study parts, the primary assessment of DCR was based on the FAS.

    For Part 1, DCR was calculated based on data from the ICR

    Measured: Number (%) of subjects with ≥ 1 visit response of CR or PR, or with SD for a minimum of 12 weeks (± 5 days) from randomization.

  6. Tumor Size - Part 1

    Part 1: The percentage change from baseline in tumor size at Week 12 (%ΔTSWk12) was a secondary endpoint for Part 1 and was used to present waterfall plots of the target lesion data in the Evaluable for Response (EFR) Population

    Measured: Week 12

  7. Number of Participants With Clinically Significant Laboratory Tests- Safety Lead-in

    Clinical laboratory tests (hematology, clinical chemistry, urinalysis) - Number of Participants with Clinically Significant Laboratory Tests.

    Measured: Subject screening visit to 28 days post last study drug administration

  8. Number of Participants With Clinically Significant Laboratory Tests - Part 1

    Clinical laboratory tests (hematology, clinical chemistry, urinalysis) - Number of Participants with Clinically Significant Laboratory Tests.

    Measured: Subject screening visit to 28 days post last study drug administration

  9. Number of Participants With Clinically Significant Change in Vital Signs and Physical Examinations - Safety Lead-In

    Number of participants with clinically significant change in vital signs (blood pressure [diastolic and systolic], heart rate, respiratory rate, body temperature) and physical examination.

    Measured: Subject screening visit to 28 days post last study drug administration

  10. Number of Participants With Clinically Significant Change in Vital Signs and Physical Examinations - Part 1

    Number of participants with clinically significant change in vital signs (blood pressure [diastolic and systolic], heart rate, respiratory rate, body temperature) and physical examination.

    Measured: Subject screening visit to 28 days post last study drug administration

  11. Number of Participants With ECG Parameters of Interest - Safety Lead-In

    Number of participants with ECG parameters of interest: Max. on-treatment QTcF Value: >450 to 480 msec, max. on-treatment QTcF Value: >480 to 500 msec, max. on-treatment QTcF Value: >500 msec, max. on-treatment QTcB Value: >450 to 480 msec, max. on-treatment QTcB Value: >480 to 500 msec, max. on-treatment QTcB Value: >500 msec, max. QTcF CFB Value: >30 to 60 msec, max. QTcF CFB Value: >60 msec, max. QTcB CFB Value: >30 to 60 msec, max. QTcB CFB Value: >60 msec.

    Measured: Subject screening visit to 28 days post last study drug administration

  12. Number of Participants With ECG Parameters of Interest - Part 1

    Number of participants with ECG parameters of interest: Max. on-treatment QTcF Value: <=450 msec, max. on-treatment QTcF Value: >450 to 480 msec, max. on-treatment QTcF Value: >480 to 500 msec, max. on-treatment QTcF Value: >500 msec, max. on-treatment QTcB Value: <=450 msec, max. on-treatment QTcB Value: >450 to 480 msec, max. on-treatment QTcB Value: >480 to 500 msec, max. on-treatment QTcB Value: >500 msec, max. QTcF CFB Value: <=30 msec, max. QTcF CFB Value: >30 to 60 msec, max. QTcF CFB Value: >60 msec, max. QTcB CFB Value: <=30 msec, max. QTcB CFB Value: >30 to 60 msec, max. QTcB CFB Value: >60 msec.

    Measured: Subject screening visit to 28 days post last study drug administration

  13. ECOG Performance Status - Part 1

    Eastern Cooperative Oncology Group (ECOG) Performance was clinically graded based on the following:

    Grade 0 = Normal activity. Fully active, able to carry on all pre-disease performance without restriction.

    Grade 1 = Symptoms, but ambulatory. Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (e.g., light housework, office work).

    Grade 2 = In bed < 50% of the time. Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours.

    Grade 3 = In bed > 50% of the time. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.

    Grade 4 = 100% bedridden. Completely disabled. Cannot carry on any self- care. Totally confined to bed or chair.

    Grade 5 = Death

    Measured: Subject screening visit to 28 days post last study drug administration

Timeline

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

  1. First posted28 Mar 2017
  2. Study start4 Jul 2017
  3. Primary completion12 Nov 2019
  4. Study completion17 Apr 2020

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Treatment: protocol designed to evaluate one or more interventions for treating a disease, syndrome or condition
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
151 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03093870
Sponsor's protocol ID
ASLAN001-009
Acronym
TreeTopp
Status last verified
Jun 2021
First submitted
16 Mar 2017
Last updated
3 Aug 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Varlitinib and Capecitabine in people with Biliary Tract Cancer, run by ASLAN Pharmaceuticals at 21 sites in 11 countries.

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 19 inclusion and 19 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: finished, as of the sponsor's last update on 3 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in United States, Australia, China, Hong Kong, Hungary and 6 more countries. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) - Part 1 (time frame: Data obtained up until progression, or until last evaluable assessment in the absence of progression, regardless of whether subjects discontinued treatment or received a subsequent therapy prior to progression, up to 2 years.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 3 Aug 2021.

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