Apatinib for Advanced Biliary Carcinoma

This is a phase II open-label, one-arm, single-center study of apatinib for eligible patients with advanced biliary tract carcinoma after the first-line treatment failure. A total of 55 patients is planned for enrollment. The time for enrollment is from Nov 2017 to Nov 2020, the the follow-up will be ended after Nov 2021. Patients in the study would receive oral apatinib 500-750mg qd until progression of disease.

Sex

All

Minimum age

18 Years

Maximum age

70 Years

Inclusion Criteria:

1. Patients age between 18 and 70 years
2. Histologically confirmed advanced biliary tract carcinoma (BTC) or metastatic BTC
3. Prior lack of response or intolerance to at least one chemotherapeutic regimens (including gemcitabine).
4. At least one measurable lesion as defined by RECIST 1.1
5. An Eastern Cooperative Oncology Group performance status of 0 to 2
6. Life expectancy ≥ 12 weeks
7. For those who received other anti-tumor treatment, the damage should have been restored, with the time interval from last dose of nitroso or mitomycin≥6 weeks and interval from last dose of other cytotoxic drugs, radiation or surgery (the wound should be healed completely) ≥4 weeks.
8. Acceptable hematologic, hepatic, and renal function within 7 days from screening： the blood ANC count≥1.5x109 /L; hemoglobin ≥ 9.0 g/dl，the blood platelet count≥80 x109 /L, total bilirubin \< 1.5 x ULN, ALT and AST\< 2.5 x ULN(\< 5 x ULN for patients with live metastasis), serum creatinine≤1 x ULN，endogenous creatinine clearance rate \>50ml/min
9. Women of reproductive age need to take effective contraceptive measures

Exclusion Criteria:

1. With other malignant tumor in 5 years，except for cured cervical carcinoma in situ or basal cell carcinoma.
2. Uncontrolled blood pressure on medication (140/90 mmHg); patients with \> Grade 1 coronary heart disease, cardiac arrhythmias or cardiac dysfunction
3. Symptomatic brain or meningeal metastasis
4. History of uncontrolled seizures, central nervous system dysfunction or mental disorder
5. Uncontrolled pleural or peritoneal effusion
6. Undergoing dialysis
7. Severe or uncontrolled infection
8. With multiple factors that affecting oral administration
9. Abnormal coagulation function or those receiving thrombolytics or anticoagulants
10. Patients with tendency of gastrointestinal hemorrhage, including active peptic ulcer with fecal occult blood ++, hematemesis or melena within 3 months
11. Participation in other drug clinical trials within 4 weeks
12. Weight below 40kg
13. urine protein ≥2+

• BACKGROUNDCereda S, Belli C, Rognone A, Mazza E, Reni M. Second-line therapy in advanced biliary tract cancer: what should be the standard? Crit Rev Oncol Hematol. 2013 Nov;88(2):368-74. doi: 10.1016/j.critrevonc.2013.05.010. Epub 2013 Jun 17. PMID 23786845
• BACKGROUNDValle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010 Apr 8;362(14):1273-81. doi: 10.1056/NEJMoa0908721. PMID 20375404
• BACKGROUNDLi J, Qin S, Xu J, Guo W, Xiong J, Bai Y, Sun G, Yang Y, Wang L, Xu N, Cheng Y, Wang Z, Zheng L, Tao M, Zhu X, Ji D, Liu X, Yu H. Apatinib for chemotherapy-refractory advanced metastatic gastric cancer: results from a randomized, placebo-controlled, parallel-arm, phase II trial. J Clin Oncol. 2013 Sep 10;31(26):3219-25. doi: 10.1200/JCO.2013.48.8585. Epub 2013 Aug 5. PMID 23918952
• BACKGROUNDLi J, Qin S, Xu J, Xiong J, Wu C, Bai Y, Liu W, Tong J, Liu Y, Xu R, Wang Z, Wang Q, Ouyang X, Yang Y, Ba Y, Liang J, Lin X, Luo D, Zheng R, Wang X, Sun G, Wang L, Zheng L, Guo H, Wu J, Xu N, Yang J, Zhang H, Cheng Y, Wang N, Chen L, Fan Z, Sun P, Yu H. Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction. J Clin Oncol. 2016 May 1;34(13):1448-54. doi: 10.1200/JCO.2015.63.5995. Epub 2016 Feb 16. PMID 26884585
• BACKGROUNDPeng H, Zhang Q, Li J, Zhang N, Hua Y, Xu L, Deng Y, Lai J, Peng Z, Peng B, Chen M, Peng S, Kuang M. Apatinib inhibits VEGF signaling and promotes apoptosis in intrahepatic cholangiocarcinoma. Oncotarget. 2016 Mar 29;7(13):17220-9. doi: 10.18632/oncotarget.7948. PMID 26967384
• DERIVEDWang C, Huang M, Geng Q, Li W, Chang J, Tang W, Guo W. Apatinib for patients with metastatic biliary tract carcinoma refractory to standard chemotherapy: results from an investigator-initiated, open-label, single-arm, exploratory phase II study. Ther Adv Med Oncol. 2021 Aug 31;13:17588359211039047. doi: 10.1177/17588359211039047. eCollection 2021.