Study of Combination Therapy of D07001-Softgel Capsules and Xeloda/TS-1 in Subjects With Advanced Biliary Tract Cancer

Prior treatment

• Have prior chemotherapy regimen other than first line gemcitabine and cisplatin-based therapy for unresectable metastatic or locally advanced BTC Note: prior fluoropyrimidine base (including capecitabine, carmofur (HCFU), doxifluridine, fluorouracil (5-FU), and tegafur) chemotherapy (including fluoropyrimidine monotherapy or combination therapy) are allowed as postsurgical adjuvant therapy.
• Diagnosis of active malignancy other than BTC within the past 2 years, except nonmelanoma skin carcinoma and carcinoma-in-situ of uterine cervix treated with curative intent
• Prior discontinuation of gemcitabine because of pulmonary or hepatic toxicity or hemolytic uremic syndrome (HUS) or hypersensitivity, allergic reaction, or intolerance
• Prior discontinuation of fluoropyrimidine because of any unexpected or severe reaction.
• Treatment with brivudine, sorivudine, or its chemically-related analogs ≤ 28 days prior to the date of enrollment.
• Residual toxicity from prior chemotherapy or CCRT that is Grade ≥2 (residual Grade 2 neuropathy and alopecia are permitted)
• Major surgery or definitive ablation-intent (excluding palliative radiotherapy for bone metastasis) radiation therapy within the past 28 days
• Received an investigational agent within 28 days of enrollment
• Received yellow fever vaccine or other live attenuated vaccine(s) within the 4 weeks prior to screening

Other illness

• Any GI disorder which would significantly impede absorption of an oral agent
• Any active disease or condition that would not permit compliance with the protocol
• Clinically significant cardiovascular disease (e.g., uncontrolled hypertension, unstable angina, congestive heart failure, or New York Heart Association \[NYHA\] Grade 2 or greater), or uncontrolled serious cardiac arrhythmia
• Have documented cerebrovascular disease. Subjects with the disease may be excluded, but if the investigator assesses that they are asymptomatic or well controlled could be enrolled.
• Have a seizure disorder not controlled on medication (based on decision of Investigator)
• Have an uncontrolled active viral, bacterial, or systemic fungal infection
• Known human immunodeficiency virus (HIV) infection
• Have HBsAg (hepatitis B surface antigen) positive with HBV-DNA ≥2000 copies/ml and/or anti-HCV antibody (HCV) positive with HCV-RNA positive.
• History of drug or alcohol abuse within last year
• Have any other serious medical condition that, in the Investigator's medical opinion, would preclude safe participation in, and compliance with, a clinical trial

Lab values

• Known or suspected hypersensitivity to capecitabine, tegafur, gimeracil, oteracil potassium, oxaliplatin or other platinum compounds, leucovorin products, folic acid or folinic acid, 5-fluorouracil or their excipients.

Other

• Under flucytosine treatment.
• Known brain or leptomeningeal metastases

• Male or female patients aged 18 years or older at screening (aged 20 years or older in Taiwan)
• Histopathological or cytologic diagnosis of unresectable metastatic or locally advanced BTC (cholangiocarcinoma, gallbladder cancer or ampullary carcinoma)
• Subject must have failed from first line gemcitabine and cisplatin-based chemotherapy
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1
• Life expectancy is \>12 weeks
• Adequate bone marrow function, demonstrated by:
  • Absolute neutrophil count (ANC) ≥1,500 cell/mm3
  • Platelet count ≥ 100,000 cells/mm3
  • Hemoglobin ≥ 9 g/dL
• Adequate liver function, demonstrated by:
  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 x upper limit of normal (ULN), or ≤5.0 x ULN in the case of liver metastases
  • Total bilirubin ≤1.5 x ULN
  • Albumin ≥3.0 g/dL
  • International normalized ratio (INR) \<1.5
• Adequate renal function, demonstrated by:
  • Serum creatinine ≤1.5 x ULN
  • Creatinine clearance ≥ 50mL/min calculated by Cockcroft-Gault formula or eGFR ≥ 50mL/min/1.73m2 by 2021 CKD-EPI Creatinine Equation
• A negative serum pregnancy test at screening and is not breastfeeding in woman of childbearing potential
• Women of childbearing potential or male subjects must use a medically acceptable form of contraception as 2 barrier methods (e.g., combination of condom, diaphragm, or intrauterine device), hormonal contraception (estrogen or progesterone agents) or 1 barrier method in combination with spermicide. Birth control is required 1 month prior to screening, for the duration of their study participation, and for 1 month after the end of the study; female partners of male subjects must adhere to the same birth control methods.
• Provision of a signed and dated written Informed Consent Form (ICF) prior to any study specific procedures
• Subject is willing to comply with protocol-required visit schedule and visit requirements
• No more than 60 days have elapsed between completion of the prior line of chemotherapy or CCRT and enrollment
• Subject has not received other chemotherapy since first-line treatment