Biliary Drainage Plus HAIC in Locally Advanced pCCA

Perihilar Cholangiocarcinoma Clinical Trial

Official title:

Prospective Multicentre Trial of Biliary Drainage Plus Hepatic Arterial Infusion Chemotherapy Versus Biliary Drainage Plus Best Supportive Care in Locally Advanced Perihilar Cholangiocarcinomas.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05024513
• Other study ID #: DRAIC
• Status: Recruiting
• Phase: Phase 2
• Start date: November 1, 2021
• Est. completion date: December 31, 2025

Study information

• Verified date: May 2023
• Source: Peking University
• Contact: Xiaodong Wang
• Phone: 18611586227
• Email: xiaodongw75[@]yahoo.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Biliary drainage and stent placement remains to be the main palliative treatment choice for advanced perihiliar cholangiocarcinoma (pCCA), and the life expectancy is only 4-6 months. Previous single center prospective phase 2 trial showed that hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin and 5-fluorouracil was an encouraging treatment choice for advanced pCCA due to its high tumor control, survival benefit, and low toxicity. Thus, the multicenter prospective controlled trial was designed to explore and confirm the survival benefit of biliary drainage plus hepatic arterial infusion chemotherapy with oxaliplatin and 5-fluorouracil compared with biliary drainage plus best support care treatment in locally advanced pCCA patients.

Description:

When a patient is not eligible for surgery, chemotherapy with gemcitabine and cisplatin can be considered for advanced biliary tract cancer. However, in the Advanced Biliary Tract Cancer, or ABC-02 trial in patients with pCCA, the efficacy of this regimen was not significantly higher than that of gemcitabine alone. Therefore, an optimal chemotherapeutic regimen has not been established for this subtype of cholangiocarcinoma. Currently, biliary drainage and stent placement remains to be the main palliative treatment choice, and the life expectancy is only 4-6 months. Previous single center prospective phase 2 trial showed that HAI with oxaliplatin and 5-fluorouracil was an encouraging treatment choice for advanced PCC due to its high tumor control, survival benefit, and low toxicity. So the multicenter prospective controlled trial was designed to explore and confirm the survival benefit of biliary drainage plus hepatic arterial infusion of oxaliplatin and 5-fluorouracil compared with biliary drainage plus best support care treatment in locally advanced pCCA patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 127
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Locally advanced perihilar cholangiocarcinoma proved by histology or cytology.

2. Locally advanced unresectable perihilar cholangiocarcinoma, decided by hepatobiliary doctor and radiologist.

3. Age from 18 years old to 75 years old.

4. The performance of Eastern Cooperative Oncology Group (ECOG) <2

5. Child-Pugh A or Child-Pugh B (= grade 7).

6. Expectant survival time = 3 months.

7. Baseline blood count test and blood biochemical must meet following criteria:

1. Hemoglobin = 90 g/L;

2. Absolute neutrophil count = 1.5×10^9/L;

3. Blood platelet count = 100×10^9/L;

4. Serum creatinine = 1.5 times of ULN;

5. Albumin = 30 g/L

8. Patients sign informed consent.

Exclusion Criteria:

1. Allergic to contrast agent.

2. Pregnant or lactational.

3. Allergic to 5-fluorouracil, or have metabolic disorder of 5-fluorouracil.

4. Previous systematic chemotherapy or radiotherapy.

5. Patients with complications such as bile leakage and bleeding after PTCD

6. N2 lymphatic metastasis, extrahepatic metastasis, or coinstantaneous a lot of malignant hydrothorax or ascites.

7. History of organ transplantation.

8. Coinstantaneous infection and need anti-infection therapy.

9. Coinstantaneous peripheral nervous system disorder or with history of obvious mental disorder and central nervous system disorder.

10. Diagnosed other kinds of malignant within 5 years, except for non-melanoma skin cancer and carcinoma in situ of cervix.

11. Without legal capacity.

12. Uncorrectable coagulation disorder.

13. Obvious abnormal in ECG or obvious clinical symptoms of heartdisease, like congestive heart failure (CHF), coronary heart disease with obvious clinical symptoms, unmanageable arrhythmia and hypertension.

14. Severe liver disease (like cirrhosis), renal disease, respiratory disease,unmanageable diabetes or other kinds of systematic disease.

Related Conditions & MeSH terms

• Cholangiocarcinoma
• Klatskin Tumor
• Perihilar Cholangiocarcinoma

Intervention

Drug:
• oxaliplatin and 5-fluorouracil
Intra-arterial chemotherapy consisted of Oxaliplatin (40mg/m2 for 2 hours), 5-fluorouracil (800 mg/ m2 for22 hours) on days 1-3 every 4 weeks.

Procedure:
• Biliary Drainage
External biliary drainage, or biliary stent placement; Biliary stent placement plus Iodine-125 seed strands is allowed

Other:
• Best Supportive Care
Nutrition support, symptomatic treatment, and other supportive treatments

Procedure:
• External biliary drainage
External biliary drainage

Locations

Country	Name	City	State
China	Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education),Peking University Cancer Hospital and Institute	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University

Country where clinical trial is conducted

China, 

References & Publications (9)

Banales JM, Cardinale V, Carpino G, Marzioni M, Andersen JB, Invernizzi P, Lind GE, Folseraas T, Forbes SJ, Fouassier L, Geier A, Calvisi DF, Mertens JC, Trauner M, Benedetti A, Maroni L, Vaquero J, Macias RI, Raggi C, Perugorria MJ, Gaudio E, Boberg KM, Marin JJ, Alvaro D. Expert consensus document: Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA). Nat Rev Gastroenterol Hepatol. 2016 May;13(5):261-80. doi: 10.1038/nrgastro.2016.51. Epub 2016 Apr 20. — View Citation

Boehm LM, Jayakrishnan TT, Miura JT, Zacharias AJ, Johnston FM, Turaga KK, Gamblin TC. Comparative effectiveness of hepatic artery based therapies for unresectable intrahepatic cholangiocarcinoma. J Surg Oncol. 2015 Feb;111(2):213-20. doi: 10.1002/jso.23781. Epub 2014 Sep 1. — View Citation

Forner A, Vidili G, Rengo M, Bujanda L, Ponz-Sarvise M, Lamarca A. Clinical presentation, diagnosis and staging of cholangiocarcinoma. Liver Int. 2019 May;39 Suppl 1:98-107. doi: 10.1111/liv.14086. Epub 2019 Mar 25. — View Citation

Hu J, Zhu X, Wang X, Cao G, Wang X, Yang R. Evaluation of percutaneous unilateral trans-femoral implantation of side-hole port-catheter system with coil only fixed-catheter-tip for hepatic arterial infusion chemotherapy. Cancer Imaging. 2019 Mar 18;19(1):15. doi: 10.1186/s40644-019-0202-z. — View Citation

Nath MC, Torbenson MS, Erickson LA. Perihilar Cholangiocarcinoma. Mayo Clin Proc. 2018 Mar;93(3):397-398. doi: 10.1016/j.mayocp.2018.01.017. No abstract available. — View Citation

Park J, Kim MH, Kim KP, Park DH, Moon SH, Song TJ, Eum J, Lee SS, Seo DW, Lee SK. Natural History and Prognostic Factors of Advanced Cholangiocarcinoma without Surgery, Chemotherapy, or Radiotherapy: A Large-Scale Observational Study. Gut Liver. 2009 Dec;3(4):298-305. doi: 10.5009/gnl.2009.3.4.298. Epub 2009 Dec 31. — View Citation

Rizvi S, Khan SA, Hallemeier CL, Kelley RK, Gores GJ. Cholangiocarcinoma - evolving concepts and therapeutic strategies. Nat Rev Clin Oncol. 2018 Feb;15(2):95-111. doi: 10.1038/nrclinonc.2017.157. Epub 2017 Oct 10. — View 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. — View Citation

Wang X, Hu J, Cao G, Zhu X, Cui Y, Ji X, Li X, Yang R, Chen H, Xu H, Liu P, Li J, Li J, Hao C, Xing B, Shen L. Phase II Study of Hepatic Arterial Infusion Chemotherapy with Oxaliplatin and 5-Fluorouracil for Advanced Perihilar Cholangiocarcinoma. Radiology. 2017 May;283(2):580-589. doi: 10.1148/radiol.2016160572. Epub 2016 Nov 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse effects	Toxicities were graded according to the Common Terminology Criteria for Adverse Events, version 4.0	6 months
Primary	Overall survival	Overall survival is measured from the date of first biliary drainage to death	1 year
Secondary	Duration of jaundice remission	The time between remission of total bilirubin to less than 2 times of the upper limit of the normal value and time of rising again of bilirubin above more than 2 times of upper limit of the normal level.	1 year