Back to resultsAdjuvant Chemotherapy With Gemcitabine and Cisplatin Compared to Standard of Care After Curative Intent Resection of Biliary Tract Cancer (ACTICCA-1)
Primary Purpose
Cholangiocarcinoma, Gall Bladder Carcinoma
Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Gemcitabine
Cisplatin
Capecitabine
Sponsored by
About this trial
This is an interventional treatment trial for Cholangiocarcinoma focused on measuring adjuvant chemotherapy, cholangiocarcinoma, muscle invasive gall bladder carcinoma, translational research, multidisciplinary, AIO, DGAV, DGVS
Eligibility Criteria
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
Sites / Locations
- Bankstown Hospital
- Nepean Hospital Cancer Care
- St. George Hospital
- Prince of Wales Hospital
- Calvary Mater Newcastle
- Townsville Hospital
- Royal Brisbane and Women's Hospital
- Princess Alexandra Hospital
- Flinders Medical Centre
- Fiona Stanley Hospital Perth
- Sir Charles Gairdner Hospital
- St. John of God
- Kaiser-Franz-Josef Hospital
- Vejle Hospital
- University Medical Center Aachen
- Charite Berlin
- University Medical Center Carl Gustav Carus
- University Medical Center Essen
- Klinikum Esslingen
- University of Frankfurt
- University Medical Center Freiburg
- University Medical Center Hamburg-Eppendorf
- University of Hannover
- University of Heidelberg
- University of Saarland
- University Medical Center Jena
- Johannes Gutenberg University of Mainz
- University of Mannheim
- University of Munich Grosshadern
- University of Regensburg
- University Medical Center Tuebingen
- University of Ulm
- University Medical Center
- Istituto Nazionale dei Tumori
- Ospedale San Raffaele
- Istituto Oncologico Veneto IRCCS
- Azienda Ospedaliero Medica 2 Universitaria
- Fondazione Policlinico Gemelli, Roma
- Academic Medical Center
- University Medical Center
- Erasmus Medisch Centrum
- Universitair Medisch Centrum Utrecht
- Auckland Hospital
- Hampshire Hospitals NHS Foundation Trust
- Queen Elizabeth Hospital Birmingham
- Royal Bournemouth Hospital
- Bristol Haematology and Oncology Centre
- Addenbrooke's Hospital Cambridge
- Velindre Hospital Cardiff
- Western General Hospital Edinburgh
- Beatson West of Scotland Cancer Centre Glasgow
- James Paget University Hospitals
- Royal Surrey County Hospital Guildford
- Princess Alexandra Hospital
- Huddersfield Royal Infirmary
- Guy's and St Thomas's Hospital London
- Hammersmith Hospital London
- Royal Free Hospital London
- University College London Hospital
- Maidstone Hospital
- Christie Hospital Manchester
- Nottingham University Hospitals NHS Trust
- Churchill Hospital Oxford
- Derriford Hospital Plymouth
- Weston Park Hospital Sheffield
- Southampton General Hospital
- Clatterbridge Cancer Centre
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Gemcitabine plus Cisplatin
Capecitabine
Arm Description
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
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
Outcomes
Primary Outcome Measures
Disease free survival (DFS)
DFS
Secondary Outcome Measures
Disease free survival rate at 24 months (DFSR@24)
DSFR
Recurrence free survival
RFS
Overall survival
OS
Safety and tolerability (assessed by the rate of patients with adverse events according to NCI CTC AE v4.03)
Quality of life
QOL
Function of biliodigestive anastomosis (in terms of surgical revision, requirement for PTCD)
Rate and severity of biliary tract infections
Patterns of disease recurrence
locoregional control (assessed by the rate of patients with hepatic or locoregional recurrence)
Full Information
NCT ID
NCT02170090
First Posted
June 18, 2014
Last Updated
January 22, 2023
Sponsor
Universitätsklinikum Hamburg-Eppendorf
Collaborators
Deutsche Krebshilfe e.V., Bonn (Germany), Cancer Research UK, Australasian Gastro-Intestinal Trials Group, Dutch Cancer Society
1. Study Identification
Unique Protocol Identification Number
NCT02170090
Brief Title
Adjuvant Chemotherapy With Gemcitabine and Cisplatin Compared to Standard of Care After Curative Intent Resection of Biliary Tract Cancer
Acronym
ACTICCA-1
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)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 2014 (undefined)
Primary Completion Date
April 2023 (Anticipated)
Study Completion Date
April 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universitätsklinikum Hamburg-Eppendorf
Collaborators
Deutsche Krebshilfe e.V., Bonn (Germany), Cancer Research UK, Australasian Gastro-Intestinal Trials Group, Dutch Cancer Society
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cholangiocarcinoma, Gall Bladder Carcinoma
Keywords
adjuvant chemotherapy, cholangiocarcinoma, muscle invasive gall bladder carcinoma, translational research, multidisciplinary, AIO, DGAV, DGVS
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
789 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Gemcitabine plus Cisplatin
Arm Type
Experimental
Arm Description
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
Arm Title
Capecitabine
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
Gemcitabine 1000mg/m2
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
Cisplatin 25mg/m2
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
Capecitabine 1250mg/m2
Primary Outcome Measure Information:
Title
Disease free survival (DFS)
Description
DFS
Time Frame
Disease free survival rate at 24 months (DFSR@24)
Secondary Outcome Measure Information:
Title
Disease free survival rate at 24 months (DFSR@24)
Description
DSFR
Time Frame
24 months
Title
Recurrence free survival
Description
RFS
Time Frame
24 months
Title
Overall survival
Description
OS
Time Frame
84 months
Title
Safety and tolerability (assessed by the rate of patients with adverse events according to NCI CTC AE v4.03)
Time Frame
24 months
Title
Quality of life
Description
QOL
Time Frame
48 months
Title
Function of biliodigestive anastomosis (in terms of surgical revision, requirement for PTCD)
Time Frame
48 months
Title
Rate and severity of biliary tract infections
Time Frame
48 months
Title
Patterns of disease recurrence
Time Frame
48 months
Title
locoregional control (assessed by the rate of patients with hepatic or locoregional recurrence)
Time Frame
48 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Henning Wege
Organizational Affiliation
Universitätsklinikum Hamburg-Eppendorf
Official's Role
Principal Investigator
Facility Information:
Facility Name
Bankstown Hospital
City
Bankstown
State/Province
New South Wales
Country
Australia
Facility Name
Nepean Hospital Cancer Care
City
Kingswood
State/Province
New South Wales
Country
Australia
Facility Name
St. George Hospital
City
Kogarah
State/Province
New South Wales
Country
Australia
Facility Name
Prince of Wales Hospital
City
Randwick
State/Province
New South Wales
Country
Australia
Facility Name
Calvary Mater Newcastle
City
Waratah
State/Province
New South Wales
Country
Australia
Facility Name
Townsville Hospital
City
Douglas
State/Province
Queensland
Country
Australia
Facility Name
Royal Brisbane and Women's Hospital
City
Herston
State/Province
Queensland
Country
Australia
Facility Name
Princess Alexandra Hospital
City
Woolloongabba
State/Province
Queensland
Country
Australia
Facility Name
Flinders Medical Centre
City
Bedford Park
State/Province
South Australia
Country
Australia
Facility Name
Fiona Stanley Hospital Perth
City
Murdoch
State/Province
Western Australia
ZIP/Postal Code
6150
Country
Australia
Facility Name
Sir Charles Gairdner Hospital
City
Nedlands
State/Province
Western Australia
Country
Australia
Facility Name
St. John of God
City
Subiaco
State/Province
Western Australia
ZIP/Postal Code
6008
Country
Australia
Facility Name
Kaiser-Franz-Josef Hospital
City
Vienna
ZIP/Postal Code
1030
Country
Austria
Facility Name
Vejle Hospital
City
Vejle
Country
Denmark
Facility Name
University Medical Center Aachen
City
Aachen
Country
Germany
Facility Name
Charite Berlin
City
Berlin
Country
Germany
Facility Name
University Medical Center Carl Gustav Carus
City
Dresden
Country
Germany
Facility Name
University Medical Center Essen
City
Essen
Country
Germany
Facility Name
Klinikum Esslingen
City
Esslingen
Country
Germany
Facility Name
University of Frankfurt
City
Frankfurt
Country
Germany
Facility Name
University Medical Center Freiburg
City
Freiburg
Country
Germany
Facility Name
University Medical Center Hamburg-Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
University of Hannover
City
Hannover
Country
Germany
Facility Name
University of Heidelberg
City
Heidelberg
Country
Germany
Facility Name
University of Saarland
City
Homburg
Country
Germany
Facility Name
University Medical Center Jena
City
Jena
Country
Germany
Facility Name
Johannes Gutenberg University of Mainz
City
Mainz
Country
Germany
Facility Name
University of Mannheim
City
Mannheim
Country
Germany
Facility Name
University of Munich Grosshadern
City
Munich
Country
Germany
Facility Name
University of Regensburg
City
Regensburg
Country
Germany
Facility Name
University Medical Center Tuebingen
City
Tuebingen
Country
Germany
Facility Name
University of Ulm
City
Ulm
Country
Germany
Facility Name
University Medical Center
City
Wuerzburg
Country
Germany
Facility Name
Istituto Nazionale dei Tumori
City
Milano
Country
Italy
Facility Name
Ospedale San Raffaele
City
Milano
Country
Italy
Facility Name
Istituto Oncologico Veneto IRCCS
City
Padova
ZIP/Postal Code
35128
Country
Italy
Facility Name
Azienda Ospedaliero Medica 2 Universitaria
City
Pisa
ZIP/Postal Code
56126
Country
Italy
Facility Name
Fondazione Policlinico Gemelli, Roma
City
Rome
Country
Italy
Facility Name
Academic Medical Center
City
Amsterdam
Country
Netherlands
Facility Name
University Medical Center
City
Maastricht
Country
Netherlands
Facility Name
Erasmus Medisch Centrum
City
Rotterdam
Country
Netherlands
Facility Name
Universitair Medisch Centrum Utrecht
City
Utrecht
Country
Netherlands
Facility Name
Auckland Hospital
City
Auckland
Country
New Zealand
Facility Name
Hampshire Hospitals NHS Foundation Trust
City
Basingstoke
Country
United Kingdom
Facility Name
Queen Elizabeth Hospital Birmingham
City
Birmingham
Country
United Kingdom
Facility Name
Royal Bournemouth Hospital
City
Bournemouth
Country
United Kingdom
Facility Name
Bristol Haematology and Oncology Centre
City
Bristol
Country
United Kingdom
Facility Name
Addenbrooke's Hospital Cambridge
City
Cambridge
Country
United Kingdom
Facility Name
Velindre Hospital Cardiff
City
Cardiff
Country
United Kingdom
Facility Name
Western General Hospital Edinburgh
City
Edinburgh
Country
United Kingdom
Facility Name
Beatson West of Scotland Cancer Centre Glasgow
City
Glasgow
Country
United Kingdom
Facility Name
James Paget University Hospitals
City
Great Yarmouth
Country
United Kingdom
Facility Name
Royal Surrey County Hospital Guildford
City
Guildford
Country
United Kingdom
Facility Name
Princess Alexandra Hospital
City
Harlow
Country
United Kingdom
Facility Name
Huddersfield Royal Infirmary
City
Huddersfield
Country
United Kingdom
Facility Name
Guy's and St Thomas's Hospital London
City
London
Country
United Kingdom
Facility Name
Hammersmith Hospital London
City
London
Country
United Kingdom
Facility Name
Royal Free Hospital London
City
London
Country
United Kingdom
Facility Name
University College London Hospital
City
London
Country
United Kingdom
Facility Name
Maidstone Hospital
City
Maidstone
Country
United Kingdom
Facility Name
Christie Hospital Manchester
City
Manchester
Country
United Kingdom
Facility Name
Nottingham University Hospitals NHS Trust
City
Nottingham
Country
United Kingdom
Facility Name
Churchill Hospital Oxford
City
Oxford
Country
United Kingdom
Facility Name
Derriford Hospital Plymouth
City
Plymouth
Country
United Kingdom
Facility Name
Weston Park Hospital Sheffield
City
Sheffield
Country
United Kingdom
Facility Name
Southampton General Hospital
City
Southampton
Country
United Kingdom
Facility Name
Clatterbridge Cancer Centre
City
Wirral
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
26228433
Citation
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.
Results Reference
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Learn more about this trial
Adjuvant Chemotherapy With Gemcitabine and Cisplatin Compared to Standard of Care After Curative Intent Resection of Biliary Tract Cancer
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