Adjuvant Capecitabine vs Gemcitabine Plus Cisplatin in Resected Extrahepatic Cholangiocarcinoma

Study Overview
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Brief Summary
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There is no proven adjuvant treatment after curative surgical resection in patients with cholangiocarcinoma, although previous meta-analysis suggested potential survival benefit of adjuvant chemotherapy or radiotherapy in patients with lymph node-positive resected cholangiocarcinoma. Despite of lack of level 1 evidence and no data which regimen is optimal, adjuvant chemotherapy is widely used in daily practice setting. Based on this background, the investigators designed the randomized phase 2 trial comparing capecitabine and gemcitabine plus cisplatin in patients with resected lymph node-positive extrahepatic cholangiocarcinoma.

Official Title
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Randomized Phase 2 Study of Capecitabine vs Gemcistabine Plus Cisplatin in Patients With Resected Extrahepatic Cholangiocarcinoma With Regional Lymph Node Metastasis

Conditions
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Cholangiocarcinoma, Biliary Tract Cancer, Adjuvant Chemotherapy, Capecitabine, Gemcitabine, Cisplatin

Intervention / Treatment
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* Drug: Gemcitabine plus cisplatin
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 19 years and older Histologically documented extrahepatic cholangiocarcinoma (perihilar or distal bile duct tumor) Microscopic or macroscopic surgical resection (ie., R0 or R1 resection) Regional lymph node metastasis according to the American Joint Committee on Cancer (AJCC) 7th edition No distant metastasis Eastern Cooperative Oncology Group (ECOG) performance status 0   1 No prior chemotherapy or radiotherapy Serum CA 19-9 < 100 U/mL at the time of enrollment Adequate bone marrow function as defined by platelets ≥ 100 x 109/L and neutrophils ≥ 1.5 x 109/L Adequate renal function, with serum creatinine < 1.5 x upper limit of normal (ULN) Adequate hepatic function with serum total bilirubin < 2 mg/dL, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5 x ULN No other malignant disease apart from non-melanotic skin cancer or carcinoma in situ of the uterine cervix or any other non life-threatening cancer (i.e., prostate or thyroid cancer) except where treated with curative intent > 5 years previously without evidence of relapse Written informed consent to the study Exclusion Criteria: Medical or psychiatric conditions that compromise the patient's ability to give informed consent or to complete the protocol or a history of non-compliance Histologies other than adenocarcinoma such as mixed hepatocellular carcinoma/cholangiocarcinoma, adenosquamous carcinoma or mixed adenocarcinoma/neuroendocrine carcinoma Intrahepatic cholangiocarcinoma or gallbladder cancer Obstruction of gastrointestinal tract Active gastrointestinal bleeding Myocardial infarction within 6 months prior to the study medication, and other clinically significant heart disease (e.g., unstable angina, congestive heart failure or uncontrolled hypertension) Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardise compliance with the protocol Female subjects who are pregnant or lactating, or males and females of reproductive potential not willing or not able to employ a highly effective method of birth control/contraception to prevent pregnancy from 2 weeks before receiving study drug until 3 months after receiving the last dose of study drug. A highly effective method of contraception is defined as having a low failure rate (< 1% per year) when used consistently and correctly.

Ages Eligible for Study
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Minimum Age: 19 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Capecitabine<br>Adjuvant Capecitabine | Drug: Capecitabine<br>* Capecitabine 1,250 mg/m2 Day 1 to 14, every 3 weeks<br>|
| Experimental: Gemcitabine plus cisplatin<br>Adjuvant Gemcitabine plus Cisplatin | Drug: Gemcitabine plus cisplatin<br>* Gemcitabine 1,000 mg/m2 and cisplatin 25 mg/m2 Day 1 and 8, every 3 weeks<br>* Other names: Cisplatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year disease-free survival | Proportion of patients without disease recurrence after 2 years | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival | Median time point that 50% of study patients recur | 4 years | 
| Toxicities (Adverse events related with chemotherapy) | Adverse events related with chemotherapy | 4 years | 
| Overall survival | Median time point that 50% of study patients is alive | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cholangiocarcinoma, Adjuvant chemotherapy