Adjuvant Chemotherapy With Gemcitabine and Cisplatin Compared to Standard of Care After Curative Intent Resection of Biliary Tract Cancer

NCT02170090 | Active Not Recruiting Phase 3 DMC

• 3 other identifiers: ACTICCA-12024-517340-61-00ACTRN12615001283561
• Study Type: interventional
• Target: 789
• Locations: 7 countries
• Sites: 66

Brief Summary

This is a multicenter, prospective, randomized, controlled phase III trial designed to assess the clinical performance of gemcitabine with cisplatin and observation vs. standard of care (observation alone in stage 1 and capecitabine and observation in stage 2) in patients after curative intent resection of BTC.

Conditions

Cholangiocarcinoma; Gall Bladder Carcinoma

Keywords

adjuvant chemotherapy; cholangiocarcinoma; muscle invasive gall bladder carcinoma; translational research; multidisciplinary; AIO, DGAV, DGVS

Outcome Measures

Primary Outcomes (1)

• Disease free survival (DFS)

  DFS

  Disease free survival rate at 24 months (DFSR@24)

Secondary Outcomes (9)

• Disease free survival rate at 24 months (DFSR@24)

  24 months

• Recurrence free survival

  24 months

• Overall survival

  84 months

• Safety and tolerability (assessed by the rate of patients with adverse events according to NCI CTC AE v4.03)

  24 months

• Quality of life

  48 months

Study Arms (2)

Gemcitabine plus Cisplatin

EXPERIMENTAL

Chemotherapy will be administered on days 1 and 8 every 3 weeks, Cisplatin (25 mg per square meter of body-surface area) and Gemcitabine (1000 mg per square meter) for 24 weeks (8 cycles) and Observation

Drug: Gemcitabine; Drug: Cisplatin

Capecitabine

ACTIVE COMPARATOR

Capecitabine will be administered from day 1 to 14 every 3 weeks (1250 mg per square meter of body-surface area, twice daily) for 24 weeks (8 cycles) and Observation

Drug: Capecitabine

Interventions

Gemcitabine DRUG

Gemcitabine 1000mg/m2

Gemcitabine plus Cisplatin

Cisplatin DRUG

Cisplatin 25mg/m2

Gemcitabine plus Cisplatin

Capecitabine DRUG

Capecitabine 1250mg/m2

Capecitabine

Eligibility Criteria

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

All enrolled patients will postoperatively be assessed for eligibility for the treatment phase. Additionally patients not previously enrolled into the trial for whatever reason (e.g. incidental finding during surgery) will be evaluated for eligibility. * Histologically confirmed adenocarcinoma of biliary tract (intrahepatic, hilar or extrahepatic cholangiocarcinoma or muscle invasive gallbladder carcinoma) after radical surgical therapy with macroscopically complete resection (mixed tumor entities (HCC/CCA) are excluded) * Macroscopically complete resection (R0/1) within 6 (-16) weeks before scheduled start of chemotherapy * ECOG 0-1 * Age ≥18 years * Adequate hematologic function * Adequate liver function * Adequate renal function * No active uncontrolled infection, except chronic viral hepatitis under antiviral therapy * No concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to randomization * Negative serum pregnancy test within 7 days of starting study treatment in pre-menopausal women and women \<1 year after the onset of menopause (Note: a negative test has to be reconfirmed by a urine test, should the 7-day window be exceeded) Criteria for initial study enrolment * Written informed consent * No prior chemotherapy for cholangiocarcinoma * No previous malignancy within 3 years or concomitant malignancy, except: non-melanomatous skin cancer or adequately treated in situ cervical cancer * No severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction in the last 3 months, significant arrhythmia) * Absence of psychiatric disorder precluding understanding of information of trial related topics and giving informed consent * No serious underlying medical conditions (judged by the investigator), that could impair the ability of the patient to participate in the trial * Fertile women (\< 1 year after last menstruation) and procreative men willing and able to use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) * No pregnancy or lactation

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Universitätsklinikum Hamburg-Eppendorf: lead
• Deutsche Krebshilfe e.V., Bonn (Germany): collaborator
• Cancer Research UK: collaborator
• Australasian Gastro-Intestinal Trials Group: collaborator
• Dutch Cancer Society: collaborator

Study Sites (67)

Bankstown Hospital

Bankstown, New South Wales, Australia

Location

Nepean Hospital Cancer Care

Kingswood, New South Wales, Australia

Location

St. George Hospital

Kogarah, New South Wales, Australia

Location

Prince of Wales Hospital

Randwick, New South Wales, Australia

Location

Calvary Mater Newcastle

Waratah, New South Wales, Australia

Location

Townsville Hospital

Douglas, Queensland, Australia

Location

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, Australia

Location

Fiona Stanley Hospital Perth

Murdoch, Western Australia, 6150, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Location

St. John of God

Subiaco, Western Australia, 6008, Australia

Location

Kaiser-Franz-Josef Hospital

Vienna, 1030, Austria

Location

Vejle Hospital

Vejle, Denmark

Location

University Medical Center Hamburg-Eppendorf

Hamburg, Hamburg, 20246, Germany

Location

University Medical Center Aachen

Aachen, Germany

Location

Charite Berlin

Berlin, Germany

Location

University Medical Center Carl Gustav Carus

Dresden, Germany

Location

University Medical Center Essen

Essen, Germany

Location

Klinikum Esslingen

Esslingen am Neckar, Germany

Location

University of Frankfurt

Frankfurt, Germany

Location

University Medical Center Freiburg

Freiburg im Breisgau, Germany

Location

University of Hannover

Hanover, Germany

Location

University of Heidelberg

Heidelberg, Germany

Location

University of Saarland

Homburg, Germany

Location

University Medical Center Jena

Jena, Germany

Location

Johannes Gutenberg University of Mainz

Mainz, Germany

Location

University of Mannheim

Mannheim, Germany

Location

University of Munich Grosshadern

Munich, Germany

Location

University of Regensburg

Regensburg, Germany

Location

University Medical Center Tuebingen

Tübingen, Germany

Location

University of Ulm

Ulm, Germany

Location

University Medical Center

Würzburg, Germany

Location

Istituto Oncologico Veneto IRCCS

Padua, Padova, 35128, Italy

Location

Azienda Ospedaliero Medica 2 Universitaria

Pisa, Pisa, 56126, Italy

Location

Fondazione Policlinico Gemelli, Roma

Rome, Rome, Italy

Location

Istituto Nazionale dei Tumori

Milan, Italy

Location

Ospedale San Raffaele

Milan, Italy

Location

Academic Medical Center

Amsterdam, Netherlands

Location

University Medical Center

Maastricht, Netherlands

Location

Erasmus Medisch Centrum

Rotterdam, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, Netherlands

Location

Auckland Hospital

Auckland, New Zealand

Location

Hampshire Hospitals NHS Foundation Trust

Basingstoke, United Kingdom

Location

Queen Elizabeth Hospital Birmingham

Birmingham, United Kingdom

Location

Royal Bournemouth Hospital

Bournemouth, United Kingdom

Location

Bristol Haematology and Oncology Centre

Bristol, United Kingdom

Location

Addenbrooke's Hospital Cambridge

Cambridge, United Kingdom

Location

Velindre Hospital Cardiff

Cardiff, United Kingdom

Location

Western General Hospital Edinburgh

Edinburgh, United Kingdom

Location

Beatson West of Scotland Cancer Centre Glasgow

Glasgow, United Kingdom

Location

James Paget University Hospitals

Great Yarmouth, United Kingdom

Location

Royal Surrey County Hospital Guildford

Guildford, United Kingdom

Location

Princess Alexandra Hospital

Harlow, United Kingdom

Location

Huddersfield Royal Infirmary

Huddersfield, United Kingdom

Location

Guy's and St Thomas's Hospital London

London, United Kingdom

Location

Hammersmith Hospital London

London, United Kingdom

Location

Royal Free Hospital London

London, United Kingdom

Location

University College London Hospital

London, United Kingdom

Location

Maidstone Hospital

Maidstone, United Kingdom

Location

Christie Hospital Manchester

Manchester, United Kingdom

Location

Clatterbridge Cancer Centre

Metropolitan Borough of Wirral, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, United Kingdom

Location

Churchill Hospital Oxford

Oxford, United Kingdom

Location

Derriford Hospital Plymouth

Plymouth, United Kingdom

Location

Weston Park Hospital Sheffield

Sheffield, United Kingdom

Location

Southampton General Hospital

Southampton, United Kingdom

Location

Related Publications (1)

• Stein A, Arnold D, Bridgewater J, Goldstein D, Jensen LH, Klumpen HJ, Lohse AW, Nashan B, Primrose J, Schrum S, Shannon J, Vettorazzi E, Wege H. Adjuvant chemotherapy with gemcitabine and cisplatin compared to observation after curative intent resection of cholangiocarcinoma and muscle invasive gallbladder carcinoma (ACTICCA-1 trial) - a randomized, multidisciplinary, multinational phase III trial. BMC Cancer. 2015 Jul 31;15:564. doi: 10.1186/s12885-015-1498-0.

  PMID: 26228433 DERIVED

Related Links

• Gemox versus surveillance following surgery of localized biliary tract cancer: Results of the PRODIGE 12-ACCORD 18 (UNICANCER GI) phase III trial. Edeline, Bonnetain et al.
• Adjuvant capecitabine for biliary tract cancer: The BILCAP randomized study. Primrose, Fox et al.

MeSH Terms

Conditions

Cholangiocarcinoma; Gallbladder Neoplasms

Interventions

Gemcitabine; Cisplatin; Capecitabine

Condition Hierarchy (Ancestors)

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

• Henning Wege

  Universitätsklinikum Hamburg-Eppendorf

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2014
• First Posted: June 23, 2014
• Study Start: April 1, 2014
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (1); IT (5); AU (12); DE (19); DK (1); GB (24); NL (4)