Varlitinib Plus Capecitabine in Chinese Patients With Advanced or Metastatic Biliary Tract Cancer
Varlitinib Plus Capecitabine in Chinese Patients With Advanced or Metastatic Biliary Tract Cancer
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. Eligible patients will receive Varlitinib plus capecitabine.
Inclusion Criteria:

 1. Patients with histologically or cytologically confirmed advanced (unresectable) or
 metastatic biliary tract cancer, including intrahepatic or extrahepatic
 cholangiocarcinoma, gallbladder cancer and carcinoma of the Ampulla of Vater. This
 includes clinical diagnosis of biliary tract cancer with histological confirmation of
 adenocarcinoma.

 2. Patients who have received and failed one and only one prior line of systemic
 treatment or advanced or metastatic disease with radiologic evidence of disease
 progression. This prior line of systemic treatment must also contain gemcitabine

 3. Patients with radiographically measurable disease based on RECIST v1.1.

 4. Patients with 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).

 5. Patients who are or older than 18 years of age and of or younger than 99 years of age
 at the time when written informed consent is obtained, and are able to understand and
 willing to sign the informed consent form.

 6. Patients have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
 1.

 7. Patients with adequate organ and hematological function:

 1. Hematological function, as follows:

 -  Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

 -  Platelet count ≥ 100 x 109/L

 2. Renal functions, as follows:

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

 3. Hepatic function, as follows:

 -  Total bilirubin ≤ 1.5 x ULN

 -  AST and ALT ≤ 5 x ULN

 Exclusion Criteria:

 1. Patients are currently on or have received anti-cancer therapy within the past 3
 weeks.

 2. Patients are currently on or have received radiation or local treatment within the
 past 3 weeks for the target lesion(s).

 3. Patients have had major surgical procedures within 14 days prior to study entry.

 4. Patients have a metastatic brain lesion(s), including asymptomatic and well controlled
 lesion(s).

 5. Patients have malabsorption syndrome, diseases significantly affecting
 gastrointestinal function, resection of the stomach or small bowel, or difficulty in
 swallowing and retaining oral medications.

 6. Patients 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.

 7. Patients 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).

 8. Female patients are pregnant or breast feeding.

 9. Patients who 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 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.

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

 11. Patients 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 cancer treatment.

 12. Patients have a known positive test for HIV, active hepatitis C, or hepatitis B
 infection with hepatitis B virus deoxyribonucleic acid exceeding 2000 IU/mL.

 13. Patients have a known history of drug addiction within last 1 year, on the basis that
 there could be a higher risk of non-compliance to investigational product.

 14. Patients need continuous treatment with proton pump inhibitors during the study
 period.

 15. Patients have a baseline corrected QT interval QTc> 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, > grade 2 Canadian cardiovascular society angina pectoris,
 or receiving quinidine, procainamide, disopyramide, amiodarone, dronedarone, arsenic,
 dofetilide, or sotalol methadone.