Adjuvant Capecitabine vs Gemcitabine Plus Cisplatin in Resected Extrahepatic Cholangiocarcinoma

NCT03079427 | Completed Phase 2

• 1 other identifier: Asan-ONCHBP-2017-001
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cholangiocarcinoma; Biliary Tract Cancer; Adjuvant Chemotherapy; Capecitabine; Gemcitabine; Cisplatin

Keywords

Cholangiocarcinoma; Adjuvant chemotherapy

Outcome Measures

Primary Outcomes (1)

• 2-year disease-free survival

  Proportion of patients without disease recurrence after 2 years

  2 years

Secondary Outcomes (3)

• Disease-free survival

  4 years

• Toxicities (Adverse events related with chemotherapy)

  4 years

• Overall survival

  4 years

Study Arms (2)

Capecitabine

ACTIVE COMPARATOR

Adjuvant Capecitabine

Drug: Capecitabine

Gemcitabine plus cisplatin

EXPERIMENTAL

Adjuvant Gemcitabine plus Cisplatin

Drug: Gemcitabine plus cisplatin

Interventions

Gemcitabine plus cisplatin DRUG

Gemcitabine 1,000 mg/m2 and cisplatin 25 mg/m2 Day 1 and 8, every 3 weeks

Also known as: Gemcitabine, Cisplatin

Gemcitabine plus cisplatin

Capecitabine DRUG

Capecitabine 1,250 mg/m2 Day 1 to 14, every 3 weeks

Capecitabine

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Asan Medical Center: lead
• Bundang CHA Hospital: collaborator
• Seoul St. Mary's Hospital: collaborator
• Severance Hospital: collaborator

Study Sites (1)

Asan Medical Center, University of Ulsan College of Medicine

Seoul, 05505, South Korea

Location

Related Publications (8)

• Horgan AM, Amir E, Walter T, Knox JJ. Adjuvant therapy in the treatment of biliary tract cancer: a systematic review and meta-analysis. J Clin Oncol. 2012 Jun 1;30(16):1934-40. doi: 10.1200/JCO.2011.40.5381. Epub 2012 Apr 23.

  PMID: 22529261 BACKGROUND

• 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.

  PMID: 20375404 BACKGROUND

• Ramirez-Merino N, Aix SP, Cortes-Funes H. Chemotherapy for cholangiocarcinoma: An update. World J Gastrointest Oncol. 2013 Jul 15;5(7):171-6. doi: 10.4251/wjgo.v5.i7.171.

  PMID: 23919111 BACKGROUND

• Neoptolemos JP, Moore MJ, Cox TF, Valle JW, Palmer DH, McDonald AC, Carter R, Tebbutt NC, Dervenis C, Smith D, Glimelius B, Charnley RM, Lacaine F, Scarfe AG, Middleton MR, Anthoney A, Ghaneh P, Halloran CM, Lerch MM, Olah A, Rawcliffe CL, Verbeke CS, Campbell F, Buchler MW; European Study Group for Pancreatic Cancer. Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial. JAMA. 2012 Jul 11;308(2):147-56. doi: 10.1001/jama.2012.7352.

  PMID: 22782416 BACKGROUND

• Patt YZ, Hassan MM, Aguayo A, Nooka AK, Lozano RD, Curley SA, Vauthey JN, Ellis LM, Schnirer II, Wolff RA, Charnsangavej C, Brown TD. Oral capecitabine for the treatment of hepatocellular carcinoma, cholangiocarcinoma, and gallbladder carcinoma. Cancer. 2004 Aug 1;101(3):578-86. doi: 10.1002/cncr.20368.

  PMID: 15274071 BACKGROUND

• Petekkaya I, Gezgen G, Roach EC, Solak M, Gullu I. Long-term advanced cholangiocarcinoma survivor with single-agent capecitabine. J BUON. 2012 Oct-Dec;17(4):796. No abstract available.

  PMID: 23335544 BACKGROUND

• Jeong H, Oh JH, Ahn HS, Ryoo BY, Kim KP, Jeong JH, Park I, Hwang DW, Lee JH, Song KB, Lee W, Kim KH, Moon DB, Song GW, Jung DH, Hong SM, Park CW, Baek IP, Cho YS, Kim K, Sung CO, Yoo C. Proteogenomic profiling predicts outcomes of adjuvant chemotherapy in extrahepatic cholangiocarcinoma. J Hepatol. 2026 Jan;84(1):122-134. doi: 10.1016/j.jhep.2025.07.031. Epub 2025 Aug 11.

  PMID: 40803577 DERIVED

• Yoo C, Jeong H, Jeong JH, Kim KP, Lee S, Ryoo BY, Hwang DW, Lee JH, Moon DB, Kim KH, Lee SS, Song TJ, Oh D, Lee MA, Chon HJ, Lee JS, Laliotis G, Rivero-Hinojosa S, Spickard E, Renner D, Dutta P, Palsuledesai CC, Sharma S, Malhotra M, Jurdi A, Liu MC. Circulating tumor DNA status and dynamics predict recurrence in patients with resected extrahepatic cholangiocarcinoma. J Hepatol. 2025 May;82(5):861-870. doi: 10.1016/j.jhep.2024.10.043. Epub 2024 Nov 10.

  PMID: 39532185 DERIVED

MeSH Terms

Conditions

Cholangiocarcinoma; Biliary Tract Neoplasms

Interventions

Gemcitabine; Cisplatin; Capecitabine

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Baek-Yeol Ryoo, MD

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 9, 2017
• First Posted: March 14, 2017
• Study Start: May 15, 2017
• Primary Completion: December 15, 2021
• Study Completion: November 15, 2022
• Last Updated: December 6, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)