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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03093870




Registration number
NCT03093870
Ethics application status
Date submitted
16/03/2017
Date registered
28/03/2017
Date last updated
3/08/2021

Titles & IDs
Public title
Varlitinib in Combination With Capecitabine for Advanced or Metastatic Biliary Tract Cancer
Scientific 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
Secondary ID [1] 0 0
ASLAN001-009
Universal Trial Number (UTN)
Trial acronym
TreeTopp
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Biliary Tract Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Biliary tree (gall bladder and bile duct)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Varlitinib
Treatment: Drugs - Capecitabine
Treatment: Drugs - Placebo (for Varlitinib)

Experimental: Varlitinib and Capecitabine -

Placebo Comparator: Placebo and Capecitabine -


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

Treatment: Drugs: Capecitabine
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.

Treatment: Drugs: Placebo (for Varlitinib)
oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR) - Part 1
Timepoint [1] 0 0
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.
Primary outcome [2] 0 0
Progression-free Survival (PFS) - Part 1
Timepoint [2] 0 0
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 outcome [1] 0 0
Object Response Rates (ORR) - Safety Lead-In
Timepoint [1] 0 0
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.
Secondary outcome [2] 0 0
Overall Survival (OS) - Part 1
Timepoint [2] 0 0
Time from the date of randomization until death due to any cause, up to 2 years
Secondary outcome [3] 0 0
Overall Survival (OS) - Safety Lead-In
Timepoint [3] 0 0
Time from the date of randomization until death due to any cause, up to 2 years
Secondary outcome [4] 0 0
Duration of Response (DoR) - Part 1
Timepoint [4] 0 0
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
Secondary outcome [5] 0 0
Disease Control Rate DCR - Part 1
Timepoint [5] 0 0
Number (%) of subjects with = 1 visit response of CR or PR, or with SD for a minimum of 12 weeks (± 5 days) from randomization.
Secondary outcome [6] 0 0
Tumor Size - Part 1
Timepoint [6] 0 0
Week 12
Secondary outcome [7] 0 0
Number of Participants With Clinically Significant Laboratory Tests- Safety Lead-in
Timepoint [7] 0 0
Subject screening visit to 28 days post last study drug administration
Secondary outcome [8] 0 0
Number of Participants With Clinically Significant Laboratory Tests - Part 1
Timepoint [8] 0 0
Subject screening visit to 28 days post last study drug administration
Secondary outcome [9] 0 0
Number of Participants With Clinically Significant Change in Vital Signs and Physical Examinations - Safety Lead-In
Timepoint [9] 0 0
Subject screening visit to 28 days post last study drug administration
Secondary outcome [10] 0 0
Number of Participants With Clinically Significant Change in Vital Signs and Physical Examinations - Part 1
Timepoint [10] 0 0
Subject screening visit to 28 days post last study drug administration
Secondary outcome [11] 0 0
Number of Participants With ECG Parameters of Interest - Safety Lead-In
Timepoint [11] 0 0
Subject screening visit to 28 days post last study drug administration
Secondary outcome [12] 0 0
Number of Participants With ECG Parameters of Interest - Part 1
Timepoint [12] 0 0
Subject screening visit to 28 days post last study drug administration
Secondary outcome [13] 0 0
ECOG Performance Status - Part 1
Timepoint [13] 0 0
Subject screening visit to 28 days post last study drug administration

Eligibility
Key inclusion criteria
Subjects will be eligible for the study if they:

1. Are of or older than the legal age in the respective countries at the time when
written informed consent is obtained

2. 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.

3. 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

4. Have received at least 6 doses of gemcitabine containing treatment in first line
(Adjuvant therapy is not regarded as 1st line therapy)

5. 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)

6. 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)

7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

8. Are able to understand and willing to sign the informed consent form

9. Have adequate organ and hematological function:

1. Hematological function, as follows:

- Absolute neutrophil count (ANC) = 1.5 × 109/L

- Platelet count = 100 × 109/L

2. Renal functions, as follows:

• Estimated glomerular filtration rate or creatinine clearance > 50 mL/min/1.73m2

3. Hepatic function, as follows:

- Albumin = 3 g/dL

- Total bilirubin = 1.5 × ULN

- Aspartate aminotransferase and alanine aminotransferase = 5 × ULN
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Subjects will be ineligible for the study if they:

1. Are currently on or have received anti-cancer therapy within the past 3 weeks before
receiving the first dose of study medication

2. 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

3. 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.)

4. Have had major surgical procedures within 14 days prior to first dose of study
medication

5. Have a known metastatic brain lesion(s), including asymptomatic and well controlled
lesion(s)

6. 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

7. 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

8. 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)

9. Are female patients who are pregnant or breast feeding

10. 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

11. Have received any investigational drug (or have used an investigational device) within
the last 14 days before receiving the first dose of study medication

12. 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

13. 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

14. 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

15. Need continuous treatment with proton pump inhibitors during the study period

16. 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

17. 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

18. 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2/Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/07/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
17/04/2020
Sample size
Target
Accrual to date
Final
151
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
There are 5 sites in different cities in Australia - Camperdown
Recruitment postcode(s) [1] 0 0
- Camperdown
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Michigan
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri
Country [4] 0 0
United States of America
State/province [4] 0 0
Nevada
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
China
State/province [10] 0 0
Nanjing
Country [11] 0 0
Hong Kong
State/province [11] 0 0
Hong Kong
Country [12] 0 0
Hungary
State/province [12] 0 0
Budapest
Country [13] 0 0
Japan
State/province [13] 0 0
Chiba
Country [14] 0 0
Korea, Republic of
State/province [14] 0 0
Seoul
Country [15] 0 0
Poland
State/province [15] 0 0
Otwock
Country [16] 0 0
Singapore
State/province [16] 0 0
Singapore
Country [17] 0 0
Spain
State/province [17] 0 0
Barcelona
Country [18] 0 0
Taiwan
State/province [18] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Other
Name
ASLAN Pharmaceuticals
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
bioRASI, LLC
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
CMIC Co, Ltd. Japan
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Syneos Health
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief 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. 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
Trial website
https://clinicaltrials.gov/ct2/show/NCT03093870
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03093870