Biliary Drainage Plus HAIC in Locally Advanced pCCA

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Perihilar Cholangiocarcinoma

Intervention / Treatment
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* Drug: oxaliplatin and 5-fluorouracil
* Procedure: Biliary Drainage
* Other: Best Supportive Care
* Procedure: External biliary drainage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Locally advanced perihilar cholangiocarcinoma proved by histology or cytology. Locally advanced unresectable perihilar cholangiocarcinoma, decided by hepatobiliary doctor and radiologist. Age from 18 years old to 75 years old. The performance of Eastern Cooperative Oncology Group (ECOG) <2 Child-Pugh A or Child-Pugh B (≤ grade 7). Expectant survival time ≥ 3 months. Baseline blood count test and blood biochemical must meet following criteria: Hemoglobin ≥ 90 g/L; Absolute neutrophil count ≥ 1.5×10^9/L; Blood platelet count ≥ 100×10^9/L; Serum creatinine ≤ 1.5 times of ULN; Albumin ≥ 30 g/L Patients sign informed consent. Exclusion Criteria: Allergic to contrast agent. Pregnant or lactational. Allergic to 5-fluorouracil, or have metabolic disorder of 5-fluorouracil. Previous systematic chemotherapy or radiotherapy. Patients with complications such as bile leakage and bleeding after PTCD N2 lymphatic metastasis, extrahepatic metastasis, or coinstantaneous a lot of malignant hydrothorax or ascites. History of organ transplantation. Coinstantaneous infection and need anti-infection therapy. Coinstantaneous peripheral nervous system disorder or with history of obvious mental disorder and central nervous system disorder. Diagnosed other kinds of malignant within 5 years, except for non-melanoma skin cancer and carcinoma in situ of cervix. Without legal capacity. Uncorrectable coagulation disorder. 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. Severe liver disease (like cirrhosis), renal disease, respiratory disease,unmanageable diabetes or other kinds of systematic disease.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BD-HAIC (Biliary drainage & HAIC)<br>The patients enrolled in this arm would receive external percutaneous biliary drainage plus 3Cir-OFF hepatic arterial infusion chemotherapy （HAIC）with oxaliplatin and 5-fluorouracil. | Drug: oxaliplatin and 5-fluorouracil<br>* 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.<br>Procedure: External biliary drainage<br>* External biliary drainage<br>|
| Active Comparator: BD-BSC (Biliary Drainage & Best supportive care)<br>The patients enrolled in this arm would receive biliary drainage, biliary stents,or biliary stents with Iodine-125 seed strands, plus best supportive care. | Procedure: Biliary Drainage<br>* External biliary drainage, or biliary stent placement; Biliary stent placement plus Iodine-125 seed strands is allowed<br>Other: Best Supportive Care<br>* Nutrition support, symptomatic treatment, and other supportive treatments<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival is measured from the date of first biliary drainage to death | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Perihilar Cholangiocarcinoma, Hepatic arterial infusion chemotherapy, Biliary Drainage, Best Supportive Care