Adjuvant Chemotherapy With Gemcitabine and Cisplatin Compared to Standard of Care After Curative Intent Resection of Biliary Tract Cancer (ACTICCA-1)

December 4, 2023 updated by: Universitätsklinikum Hamburg-Eppendorf

Adjuvant Chemotherapy With Gemcitabine and Cisplatin Compared to Standard of Care After Curative Intent Resection of Cholangiocarcinoma and Muscle Invasive Gall Bladder Carcinoma (ACTICCA-1 Trial)

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

The ACTICCA-1 investigator initiated trial is funded by the Deutsche Krebshilfe (grant number 70110215, 70112047). With respect to data obtained in the ABC-02 trial, the combination of cisplatin and gemcitabine for 24 weeks as investigational treatment was selected. Based on adjuvant trials in pancreatic cancer (e.g. ESPAC IV) with a comparable postoperative recovery time, inclusion of patients within a maximum interval of 16 weeks between surgery and start of CTx was chosen. Gemcitabine and cisplatin has a relevantly higher cumulative dose of gemcitabine 18 vs. 12 applications and may thus be of increased efficacy compared to the gemcitabine/oxaliplatin regimen applied in the PRODIGE 12 trial.

Based on the data of the BILCAP trial showing an improvement in median overall survival for capecitabine compared to observation alone presented at the annual meeting of the American Society of Clinical Oncology on June 4th 2017 in Chicago by the British BILCAP trial group, capecitabine has evolved as the new standard of care after curative intent resection of biliary tract cancer.

Based on these data the comparative efficacy of gemcitabine/cisplatin and capecitabine had to be established.

Therefore, the ACTICCA trial was amended to compare gemcitabine and cisplatin to the newly established standard regimen in the adjuvant setting capecitabine, aiming for superiority of the combination regimen vs. the oral monotherapy This was based on the BILCAP protocol, applying the similar dosing, assessments and dose modifications as in BILCAP, including dose calculation and patient diary.

As data of recent trials like the French PRODIGE 12/ACCORD 18 trial have clearly shown that in terms of efficacy of an adjuvant chemotherapy there is no difference between cholangiocarcinoma and gall bladder carcinoma, these two subtypes are pooled and location was added as an stratification factor.

Randomization will be 1:1 with adjuvant CTx for 24 weeks and imaging every 12 weeks in the experimental arm and standard of care (capecitabine) and observation in the control arm.

The primary endpoint is DFS and secondary endpoints include recurrence free survival, OS, safety and tolerability of adjuvant CTx, quality of life, and patterns of disease recurrence.

Study Type

Interventional

Enrollment (Actual)

789

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Alexander Stein
  • Phone Number: 004940741056882
  • Email: a.stein@uke.de

Study Contact Backup

  • Name: Jun Li
  • Phone Number: 004940741058572
  • Email: j.li@uke.de

Study Locations

  • Australia
    • New South Wales
      • Bankstown, New South Wales, Australia
        • Bankstown Hospital
      • Kingswood, New South Wales, Australia
        • Nepean Hospital Cancer Care
      • Kogarah, New South Wales, Australia
        • St. George Hospital
      • Randwick, New South Wales, Australia
        • Prince of Wales Hospital
      • Waratah, New South Wales, Australia
        • Calvary Mater Newcastle
    • Queensland
      • Douglas, Queensland, Australia
        • Townsville Hospital
      • Herston, Queensland, Australia
        • Royal Brisbane and Women'S Hospital
      • Woolloongabba, Queensland, Australia
        • Princess Alexandra Hospital
    • South Australia
      • Bedford Park, South Australia, Australia
        • Flinders Medical Centre
    • Western Australia
      • Murdoch, Western Australia, Australia, 6150
        • Fiona Stanley Hospital Perth
      • Nedlands, Western Australia, Australia
        • Sir Charles Gairdner Hospital
      • Subiaco, Western Australia, Australia, 6008
        • St. John of God
  • Austria
      • Vienna, Austria, 1030
        • Kaiser-Franz-Josef Hospital
  • Denmark
      • Vejle, Denmark
        • Vejle Hospital
  • Germany
      • Aachen, Germany
        • University Medical Center Aachen
      • Berlin, Germany
        • Charité Berlin
      • Dresden, Germany
        • University Medical Center Carl Gustav Carus
      • Essen, Germany
        • University Medical Center Essen
      • Esslingen, Germany
        • Klinikum Esslingen
      • Frankfurt, Germany
        • University of Frankfurt
      • Freiburg, Germany
        • University Medical Center Freiburg
      • Hamburg, Germany, 20246
        • University Medical Center Hamburg-Eppendorf
      • Hannover, Germany
        • University of Hannover
      • Heidelberg, Germany
        • University of Heidelberg
      • Homburg, Germany
        • University of Saarland
      • Jena, Germany
        • University Medical Center Jena
      • Mainz, Germany
        • Johannes Gutenberg University of Mainz
      • Mannheim, Germany
        • University of Mannheim
      • Munich, Germany
        • University of Munich Grosshadern
      • Regensburg, Germany
        • University of Regensburg
      • Tuebingen, Germany
        • University Medical Center Tuebingen
      • Ulm, Germany
        • University of Ulm
      • Wuerzburg, Germany
        • University Medical Center
  • Italy
      • Milano, Italy
        • Ospedale San Raffaele
      • Milano, Italy
        • Istituto Nazionale dei Tumori
      • Padova, Italy, 35128
        • Istituto Oncologico Veneto IRCCS
      • Pisa, Italy, 56126
        • Azienda Ospedaliero Medica 2 Universitaria
      • Rome, Italy
        • Fondazione Policlinico Gemelli, Roma
  • Netherlands
      • Amsterdam, Netherlands
        • Academic Medical Center
      • Maastricht, Netherlands
        • University Medical Center
      • Rotterdam, Netherlands
        • Erasmus Medisch Centrum
      • Utrecht, Netherlands
        • Universitair Medisch Centrum Utrecht
  • New Zealand
      • Auckland, New Zealand
        • Auckland Hospital
  • United Kingdom
      • Basingstoke, United Kingdom
        • Hampshire Hospitals NHS Foundation Trust
      • Birmingham, United Kingdom
        • Queen Elizabeth Hospital Birmingham
      • Bournemouth, United Kingdom
        • Royal Bournemouth Hospital
      • Bristol, United Kingdom
        • Bristol Haematology and Oncology Centre
      • Cambridge, United Kingdom
        • Addenbrooke's Hospital Cambridge
      • Cardiff, United Kingdom
        • Velindre Hospital Cardiff
      • Edinburgh, United Kingdom
        • Western General Hospital Edinburgh
      • Glasgow, United Kingdom
        • Beatson West of Scotland Cancer Centre Glasgow
      • Great Yarmouth, United Kingdom
        • James Paget University Hospitals
      • Guildford, United Kingdom
        • Royal Surrey County Hospital Guildford
      • Harlow, United Kingdom
        • Princess Alexandra Hospital
      • Huddersfield, United Kingdom
        • Huddersfield Royal Infirmary
      • London, United Kingdom
        • University College London Hospital
      • London, United Kingdom
        • Guy's and St Thomas's Hospital London
      • London, United Kingdom
        • Hammersmith Hospital London
      • London, United Kingdom
        • Royal Free Hospital London
      • Maidstone, United Kingdom
        • Maidstone Hospital
      • Manchester, United Kingdom
        • Christie Hospital Manchester
      • Nottingham, United Kingdom
        • Nottingham University Hospitals NHS Trust
      • Oxford, United Kingdom
        • Churchill Hospital Oxford
      • Plymouth, United Kingdom
        • Derriford Hospital Plymouth
      • Sheffield, United Kingdom
        • Weston Park Hospital Sheffield
      • Southampton, United Kingdom
        • Southampton General Hospital
      • Wirral, United Kingdom
        • Clatterbridge Cancer Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Gemcitabine plus Cisplatin

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
Gemcitabine 1000mg/m2
Drug: Cisplatin
Cisplatin 25mg/m2
Active Comparator: Capecitabine

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
Capecitabine 1250mg/m2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease free survival (DFS)
Time Frame: Disease free survival rate at 24 months (DFSR@24)
DFS
Disease free survival rate at 24 months (DFSR@24)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease free survival rate at 24 months (DFSR@24)
Time Frame: 24 months
DSFR
24 months
Recurrence free survival
Time Frame: 24 months
RFS
24 months
Overall survival
Time Frame: 84 months
OS
84 months
Safety and tolerability (assessed by the rate of patients with adverse events according to NCI CTC AE v4.03)
Time Frame: 24 months
24 months
Quality of life
Time Frame: 48 months
QOL
48 months
Function of biliodigestive anastomosis (in terms of surgical revision, requirement for PTCD)
Time Frame: 48 months
48 months
Rate and severity of biliary tract infections
Time Frame: 48 months
48 months
Patterns of disease recurrence
Time Frame: 48 months
48 months
locoregional control (assessed by the rate of patients with hepatic or locoregional recurrence)
Time Frame: 48 months
48 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universitätsklinikum Hamburg-Eppendorf

Collaborators

Cancer Research UK
Deutsche Krebshilfe e.V., Bonn (Germany)
Australasian Gastro-Intestinal Trials Group
Dutch Cancer Society

Investigators

  • Principal Investigator: Henning Wege, Universitatsklinikum Hamburg-Eppendorf

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2014

Primary Completion (Estimated)

April 1, 2024

Study Completion (Estimated)

April 1, 2024

Study Registration Dates

First Submitted

June 18, 2014

First Submitted That Met QC Criteria

June 20, 2014

First Posted (Estimated)

June 23, 2014

Study Record Updates

Last Update Posted (Actual)

December 5, 2023

Last Update Submitted That Met QC Criteria

December 4, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTICCA-1
  • 2012-005078-70 (EudraCT Number)
  • ACTRN12615001283561 (Registry Identifier: ANZCTR (clinical trial registry))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Cholangiocarcinoma

Clinical Trials on Gemcitabine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in United Kingdom

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe