CholangiocarcinomaPhase 3ACTICCA-1NCT02170090
Adjuvant Chemotherapy With Gemcitabine and Cisplatin Compared to Standard of Care After Curative Intent Resection of Biliary Tract Cancer
A Phase 3 study testing Gemcitabine, Cisplatin and Capecitabine in people with Cholangiocarcinoma and Gall Bladder Carcinoma, run by Universitätsklinikum Hamburg-Eppendorf at 67 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cholangiocarcinoma, Gall Bladder Carcinoma
- What is being tested?
- Gemcitabine, Cisplatin and Capecitabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 789 participants
- Where
- 67 sitesin 8 countries
- Study dates
- Apr 2014to Dec 2025
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
67 sites in 8 countries.
67 sites in 8 countries
United Kingdom24 sites
Hampshire Hospitals NHS Foundation Trust
Basingstoke
Queen Elizabeth Hospital Birmingham
Birmingham
Royal Bournemouth Hospital
Bournemouth
Bristol Haematology and Oncology Centre
Bristol
Addenbrooke's Hospital Cambridge
Cambridge
Velindre Hospital Cardiff
Cardiff
Western General Hospital Edinburgh
Edinburgh
Beatson West of Scotland Cancer Centre Glasgow
Glasgow
James Paget University Hospitals
Great Yarmouth
Royal Surrey County Hospital Guildford
Guildford
Princess Alexandra Hospital
Harlow
Huddersfield Royal Infirmary
Huddersfield
Guy's and St Thomas's Hospital London
London
Hammersmith Hospital London
London
Royal Free Hospital London
London
University College London Hospital
London
Maidstone Hospital
Maidstone
Christie Hospital Manchester
Manchester
Clatterbridge Cancer Centre
Metropolitan Borough of Wirral
Nottingham University Hospitals NHS Trust
Nottingham
Churchill Hospital Oxford
Oxford
Derriford Hospital Plymouth
Plymouth
Weston Park Hospital Sheffield
Sheffield
Southampton General Hospital
Southampton
Germany19 sites
University Medical Center Aachen
Aachen
Charite Berlin
Berlin
University Medical Center Carl Gustav Carus
Dresden
University Medical Center Essen
Essen
Klinikum Esslingen
Esslingen am Neckar
University of Frankfurt
Frankfurt
University Medical Center Freiburg
Freiburg im Breisgau
University Medical Center Hamburg-Eppendorf
Hamburg, Free and Hanseatic City of Hamburg, 20246
University of Hannover
Hanover
University of Heidelberg
Heidelberg
University of Saarland
Homburg
University Medical Center Jena
Jena
Johannes Gutenberg University of Mainz
Mainz
University of Mannheim
Mannheim
University of Munich Grosshadern
Munich
University of Regensburg
Regensburg
University Medical Center Tuebingen
Tübingen
University of Ulm
Ulm
University Medical Center
Würzburg
Australia12 sites
Bankstown Hospital
Bankstown, New South Wales
Flinders Medical Centre
Bedford Park, South Australia
Townsville Hospital
Douglas, Queensland
Royal Brisbane and Women's Hospital
Herston, Queensland
Nepean Hospital Cancer Care
Kingswood, New South Wales
St. George Hospital
Kogarah, New South Wales
Fiona Stanley Hospital Perth
Murdoch, Western Australia, 6150
Sir Charles Gairdner Hospital
Nedlands, Western Australia
Prince of Wales Hospital
Randwick, New South Wales
St. John of God
Subiaco, Western Australia, 6008
Calvary Mater Newcastle
Waratah, New South Wales
Princess Alexandra Hospital
Woolloongabba, Queensland
Italy5 sites
Istituto Nazionale dei Tumori
Milan
Ospedale San Raffaele
Milan
Istituto Oncologico Veneto IRCCS
Padova, Padova, 35128
Azienda Ospedaliero Medica 2 Universitaria
Pisa, Pisa, 56126
Fondazione Policlinico Gemelli, Roma
Rome, Rome
Netherlands4 sites
Academic Medical Center
Amsterdam
University Medical Center
Maastricht
Erasmus Medisch Centrum
Rotterdam
Universitair Medisch Centrum Utrecht
Utrecht
About this study
Official title: 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.
Read the 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.
- Conditions
- Cholangiocarcinoma, Gall Bladder Carcinoma
- Being tested
- Gemcitabine, Cisplatin, Capecitabine
- Keywords
- adjuvant chemotherapy, cholangiocarcinoma, muscle invasive gall bladder carcinoma, translational research, multidisciplinary, AIO, DGAV, DGVS
- Medical subject headings
- Cholangiocarcinoma, Gallbladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GemcitabineDrug
Gemcitabine 1000mg/m2
CisplatinDrug
Cisplatin 25mg/m2
CapecitabineDrug
Capecitabine 1250mg/m2
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Capecitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease free survival (DFS)
DFS
Measured: Disease free survival rate at 24 months (DFSR@24)
Secondary outcomes (9)
Disease free survival rate at 24 months (DFSR@24)
DSFR
Measured: 24 months
Recurrence free survival
RFS
Measured: 24 months
Overall survival
OS
Measured: 84 months
Safety and tolerability (assessed by the rate of patients with adverse events according to NCI CTC AE v4.03)
Measured: 24 months
Quality of life
QOL
Measured: 48 months
Function of biliodigestive anastomosis (in terms of surgical revision, requirement for PTCD)
Measured: 48 months
Rate and severity of biliary tract infections
Measured: 48 months
Patterns of disease recurrence
Measured: 48 months
locoregional control (assessed by the rate of patients with hepatic or locoregional recurrence)
Measured: 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2014 (estimated)
- Study startApr 2014
- Primary completionDec 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CholangiocarcinomaStudies of the same condition, open and under way.
- More trials run by Universitätsklinikum Hamburg-EppendorfThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 789 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitätsklinikum Hamburg-Eppendorf
- Sponsor type
- University, hospital or other
- Collaborators
- Deutsche Krebshilfe e.V., Bonn (Germany), Cancer Research UK, Australasian Gastro-Intestinal Trials Group, Dutch Cancer Society
- Responsible party
- Sponsor
- Investigators
- Henning Wege, Principal investigator, Universitätsklinikum Hamburg-Eppendorf
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02170090
- Sponsor's protocol ID
- ACTICCA-1
- Other IDs
- 2024-517340-61-00, ACTRN12615001283561
- Acronym
- ACTICCA-1
- Status last verified
- Mar 2025
- First submitted
- 18 Jun 2014
- Last updated
- 30 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 26228433
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT02170090
- Acronym / sponsor ID
- ACTICCA-1 / ACTICCA-1
- Conditions
- Cholangiocarcinoma, Gall Bladder Carcinoma
- Keywords
- adjuvant chemotherapy, cholangiocarcinoma, muscle invasive gall bladder carcinoma, translational research, multidisciplinary, AIO, DGAV, DGVS
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 789 participants (actual)
- Lead sponsor
- Universitätsklinikum Hamburg-EppendorfUniversity, hospital or other
- Collaborators
- Deutsche Krebshilfe e.V., Bonn (Germany), Cancer Research UK, Australasian Gastro-Intestinal Trials Group, Dutch Cancer Society
- Study start
- Apr 2014
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 23 Jun 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Gemcitabine plus Cisplatin | Experimental | Drug: Gemcitabine, Drug: CisplatinChemotherapy 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 |
| Capecitabine | Active comparator | Drug: CapecitabineCapecitabine 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GemcitabineGemcitabine 1000mg/m2 | Drug | Gemcitabine plus Cisplatin |
| CisplatinCisplatin 25mg/m2 | Drug | Gemcitabine plus Cisplatin |
| CapecitabineCapecitabine 1250mg/m2 | Drug | Capecitabine |
Primary outcome
Disease free survival (DFS)
Time frame: Disease free survival rate at 24 months (DFSR@24)
DFS
9 secondary outcomes
Disease free survival rate at 24 months (DFSR@24)
Time frame: 24 months
Recurrence free survival
Time frame: 24 months
Overall survival
Time frame: 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
Quality of life
Time frame: 48 months
Function of biliodigestive anastomosis (in terms of surgical revision, requirement for PTCD)
Time frame: 48 months
Rate and severity of biliary tract infections
Time frame: 48 months
Patterns of disease recurrence
Time frame: 48 months
locoregional control (assessed by the rate of patients with hepatic or locoregional recurrence)
Time frame: 48 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2025.
- Derived from this study: PubMed 26228433Stein 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Henning Wege principal investigator
Universitätsklinikum Hamburg-Eppendorf
67 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Gemcitabine, Cisplatin and Capecitabine in people with Cholangiocarcinoma and Gall Bladder Carcinoma, run by Universitätsklinikum Hamburg-Eppendorf at 67 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 30 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 67 sites in United Kingdom, Germany, Australia, Italy, Netherlands and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease free survival (DFS) (time frame: Disease free survival rate at 24 months (DFSR@24)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02170090, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2025.