Clinical trial NCT02170090: Adjuvant Chemotherapy With Gemcitabine and Cisplatin Compared to Standard of Care After Curative Intent Resection of Biliary Tract Cancer
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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Cholangiocarcinoma
Gall Bladder Carcinoma
Keywords: adjuvant chemotherapy
cholangiocarcinoma
muscle invasive gall bladder carcinoma
translational research
multidisciplinary
AIO, DGAV, DGVS
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
Collaborators: name: Deutsche Krebshilfe e.V., Bonn (Germany)
name: Cancer Research UK
name: Australasian Gastro-Intestinal Trials Group
name: Dutch Cancer Society
First posted: 2014-06-23
Enrollment: 789
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Disease free survival (DFS)
timeFrame: Disease free survival rate at 24 months (DFSR@24)
Secondary outcomes:
measure: Disease free survival rate at 24 months (DFSR@24)
timeFrame: 24 months
measure: Recurrence free survival
timeFrame: 24 months
measure: Overall survival
timeFrame: 84 months
measure: Safety and tolerability (assessed by the rate of patients with adverse events according to NCI CTC AE v4.03)
timeFrame: 24 months
measure: Quality of life
timeFrame: 48 months
measure: Function of biliodigestive anastomosis (in terms of surgical revision, requirement for PTCD)
timeFrame: 48 months
measure: Rate and severity of biliary tract infections
timeFrame: 48 months
measure: Patterns of disease recurrence
timeFrame: 48 months
measure: locoregional control (assessed by the rate of patients with hepatic or locoregional recurrence)
timeFrame: 48 months
Other outcomes:
Locations:
city: Bankstown
country: Australia
facility: Bankstown Hospital
state: New South Wales
city: Kingswood
country: Australia
facility: Nepean Hospital Cancer Care
state: New South Wales
city: Kogarah
country: Australia
facility: St. George Hospital
state: New South Wales
city: Randwick
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Douglas
country: Australia
facility: Townsville Hospital
state: Queensland
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital Perth
state: Western Australia
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Subiaco
country: Australia
facility: St. John of God
state: Western Australia
city: Vienna
country: Austria
facility: Kaiser-Franz-Josef Hospital
city: Vejle
country: Denmark
facility: Vejle Hospital
city: Aachen
country: Germany
facility: University Medical Center Aachen
city: Berlin
country: Germany
facility: Charite Berlin
city: Dresden
country: Germany
facility: University Medical Center Carl Gustav Carus
city: Essen
country: Germany
facility: University Medical Center Essen
city: Esslingen
country: Germany
facility: Klinikum Esslingen
city: Frankfurt
country: Germany
facility: University of Frankfurt
city: Freiburg
country: Germany
facility: University Medical Center Freiburg
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf
city: Hannover
country: Germany
facility: University of Hannover
city: Heidelberg
country: Germany
facility: University of Heidelberg
city: Homburg
country: Germany
facility: University of Saarland
city: Jena
country: Germany
facility: University Medical Center Jena
city: Mainz
country: Germany
facility: Johannes Gutenberg University of Mainz
city: Mannheim
country: Germany
facility: University of Mannheim
city: Munich
country: Germany
facility: University of Munich Grosshadern
city: Regensburg
country: Germany
facility: University of Regensburg
city: Tuebingen
country: Germany
facility: University Medical Center Tuebingen
city: Ulm
country: Germany
facility: University of Ulm
city: Wuerzburg
country: Germany
facility: University Medical Center
city: Milano
country: Italy
facility: Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IRCCS
city: Pisa
country: Italy
facility: Azienda Ospedaliero Medica 2 Universitaria
city: Rome
country: Italy
facility: Fondazione Policlinico Gemelli, Roma
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Maastricht
country: Netherlands
facility: University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Auckland
country: New Zealand
facility: Auckland Hospital
city: Basingstoke
country: United Kingdom
facility: Hampshire Hospitals NHS Foundation Trust
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital Birmingham
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital Cambridge
city: Cardiff
country: United Kingdom
facility: Velindre Hospital Cardiff
city: Edinburgh
country: United Kingdom
facility: Western General Hospital Edinburgh
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre Glasgow
city: Great Yarmouth
country: United Kingdom
facility: James Paget University Hospitals
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital Guildford
city: Harlow
country: United Kingdom
facility: Princess Alexandra Hospital
city: Huddersfield
country: United Kingdom
facility: Huddersfield Royal Infirmary
city: London
country: United Kingdom
facility: Guy's and St Thomas's Hospital London
city: London
country: United Kingdom
facility: Hammersmith Hospital London
city: London
country: United Kingdom
facility: Royal Free Hospital London
city: London
country: United Kingdom
facility: University College London Hospital
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital Manchester
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Oxford
country: United Kingdom
facility: Churchill Hospital Oxford
city: Plymouth
country: United Kingdom
facility: Derriford Hospital Plymouth
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital Sheffield
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Wirral
country: United Kingdom
facility: Clatterbridge Cancer Centre
Study officials:
affiliation: Universitätsklinikum Hamburg-Eppendorf
name: Henning Wege
role: PRINCIPAL_INVESTIGATOR
References:
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.