Clinical trial NCT03427242: Apatinib for Advanced Biliary Carcinoma
Official title: A Phase II Study of Apatinib Treatment for Advanced Biliary Tract Carcinoma After Failure of the First-line Chemotherapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Biliary Tract Neoplasms
Keywords: biliary tract carcinoma
apatinib
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2018-02-09
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: apatinib
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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+

Primary outcomes:
measure: PFS
timeFrame: from the time signing of ICF until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Secondary outcomes:
measure: OS
timeFrame: from the time signing of ICF until the date of death from any cause, assessed up to 48 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Shanghai Cancer Hospital
name: Weijian Guo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cereda 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.
citation: Valle 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.
citation: Li 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.
citation: Li 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.
citation: Peng 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.
citation: Wang 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.