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

Cholangiocarcinoma Clinical Trial

— 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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02170090
• Other study ID #: ACTICCA-1
• Secondary ID: 2012-005078-70AC
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 2014
• Est. completion date: April 2024

Study information

• Verified date: December 2023
• Source: Universitätsklinikum Hamburg-Eppendorf
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 789
• Est. completion date: April 2024
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Cholangiocarcinoma
• Gall Bladder Carcinoma
• Gallbladder Neoplasms
• Urinary Bladder Neoplasms

Intervention

Drug:
• Gemcitabine
Gemcitabine 1000mg/m2
• Cisplatin
Cisplatin 25mg/m2
• Capecitabine
Capecitabine 1250mg/m2

Locations

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

Sponsors (5)

Lead Sponsor	Collaborator
Universitätsklinikum Hamburg-Eppendorf	Australasian Gastro-Intestinal Trials Group, Cancer Research UK, Deutsche Krebshilfe e.V., Bonn (Germany), Dutch Cancer Society

Countries where clinical trial is conducted

Australia,  Austria,  Denmark,  Germany,  Italy,  Netherlands,  New Zealand,  United Kingdom, 

Outcome

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