Adjuvant chemotherapy with gemcitabine and cisplatin compared to standard of care after curative intent resection of cholangiocarcinoma and muscle invasive gallbladder carcinoma (ACTICCA-1 trial)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Medical Center Hamburg-Eppendorf

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 Nov 2024 → 31 Dec 2025

Decision date (initial)

2024-11-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Deutsche Krebshilfe e. V. , medac GmbH, Cancer Research UK & KWF Kanker Bestrijding, The Netherlands

External identifiers

EU CT number

2024-517340-61-00

EudraCT number

2012-005078-70

ClinicalTrials.gov

NCT02170090

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

The primary objective of this study is to evaluate the efficacy of gemcitabine and cisplatin compared with standard of care (observation alone in stage 1 and capecitabine and observation in stage 2) in patients with BTC after complete resection in terms of DFS

Secondary objectives 1

1. Secondary objectives are safety and tolerability of the treatment as well as RFS and OS, quality of life, function of biliodigestive anastomoses, and evaluation of the quantity and quality of information patients have gained after the informed consent as well as of the involvement of patients in the decision-making process (shared decision making).

Conditions and MedDRA coding

Patients after curative intent resection of cholangiocarcinoma (intrahepatic, hilar or distal) or muscle invasive gallbladder carcinoma (without evidence of metastatic disease).

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Eligibility criteria for enrolment phase 1. Suspicion of or histologically/cytologically confirmed adenocarcinoma of biliary tract (intrahepatic, hilar or extrahepatic cholangiocarcinoma or muscle invasive gallbladder carcinoma) scheduled for radical surgical therapy 2. Written informed consent 3. No prior chemotherapy for biliary tract cancer 4. No previous malignancy within 3 years or concomitant malignancy, except: those with a 5 year overall survival rate of more than 90%, e.g. non-melanomatous skin cancer or adequately treated in situ cervical cancer 5. 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) 6. Absence of psychiatric disorder precluding understanding of information of trial related topics and giving informed consent 7. No serious underlying medical conditions (judged by the investigator), that could impair the ability of the patient to participate in the trial 8. 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) 9. No pregnancy or lactation
2. Eligibility criteria for treatment phase (before randomization) 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. 1. Histologically confirmed non metastatic 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) including resection of adjacent lymph nodes (according to appendix H) 2. Macroscopically complete resection (R0/1) within 6 (-16) weeks before scheduled start of chemotherapy 3. ECOG 0-1 4. Age ≥18 years 5. Adequate hematologic function: ANC 1.5 x 109/L, platelets 100 x109/L, hemoglobin 9 g/dl or 5.59 mmol/L 6. Adequate liver function as measured by serum transaminases (AST and ALT) £5 x ULN and bilirubin £3 x ULN 7. Adequate renal function, i.e. serum creatinine £1.5 x ULN, glomerular filtration rate ≥ 50 ml/min (determination of GFR according to local institutional standards, e.g. MDRD, (Appendix E)) 8. No active uncontrolled infection, except chronic viral hepatitis under antiviral therapy 9. No concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to randomization 10. 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)
3. Criteria for initial study enrolment 11. Written informed consent 12. No prior chemotherapy for biliary tract cancer cancer 14. 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) 15. Absence of psychiatric disorder precluding understanding of information of trial related topics and giving informed consent 16. No serious underlying medical conditions (judged by the investigator), that could impair the ability of the patient to participate in the trial 17. 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) 18. No pregnancy or lactation 13. No previous malignancy within 3 years or concomitant malignancy, except: those with a 5 year overall survival rate of more than 90%, e.g. non-melanomatous skin cancer or adequately treated in situ cervical

Exclusion criteria 3

1. Eligibility criteria for enrolment phase 1. Suspicion of or histologically/cytologically confirmed adenocarcinoma of biliary tract (intrahepatic, hilar or extrahepatic cholangiocarcinoma or muscle invasive gallbladder carcinoma) scheduled for radical surgical therapy 2. Written informed consent 3. No prior chemotherapy for biliary tract cancer 4. No previous malignancy within 3 years or concomitant malignancy, except: those with a 5 year overall survival rate of more than 90%, e.g. non-melanomatous skin cancer or adequately treated in situ cervical cancer 5. 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) 6. Absence of psychiatric disorder precluding understanding of information of trial related topics and giving informed consent 7. No serious underlying medical conditions (judged by the investigator), that could impair the ability of the patient to participate in the trial 8. 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) 9. No pregnancy or lactation
2. Eligibility criteria for treatment phase (before randomization) 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. 1. Histologically confirmed non metastatic 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) including resection of adjacent lymph nodes (according to appendix H) 2. Macroscopically complete resection (R0/1) within 6 (-16) weeks before scheduled start of chemotherapy 3. ECOG 0-1 4. Age ≥18 years 5. Adequate hematologic function: ANC 1.5 x 109/L, platelets 100 x109/L, hemoglobin 9 g/dl or 5.59 mmol/L 6. Adequate liver function as measured by serum transaminases (AST and ALT) £5 x ULN and bilirubin £3 x ULN 7. Adequate renal function, i.e. serum creatinine £1.5 x ULN, glomerular filtration rate ≥ 50 ml/min (determination of GFR according to local institutional standards, e.g. MDRD, (Appendix E)) 8. No active uncontrolled infection, except chronic viral hepatitis under antiviral therapy 9. No concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to randomization 10. 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)
3. Criteria for initial study enrolment 11. Written informed consent 12. No prior chemotherapy for biliary tract cancer 13. No previous malignancy within 3 years or concomitant malignancy, except: those with a 5 year overall survival rate of more than 90%, e.g. non-melanomatous skin cancer or adequately treated in situ cervical cancer 14. 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) 15. Absence of psychiatric disorder precluding understanding of information of trial related topics and giving informed consent 16. No serious underlying medical conditions (judged by the investigator), that could impair the ability of the patient to participate in the trial 17. 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) 18. No pregnancy or lactation

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease free survival (DFS)

Secondary endpoints 9

1. Disease free survival rate at 24 months (DFSR@24)
2. Recurrence free survival (RFS)
3. Overall survival (OS)
4. Safety and tolerability of adjuvant chemotherapy
5. Quality of life (QoL)
6. Function of biliodigestive anastomosis (in terms of surgical revision, requirement for PTCD)
7. Rate and severity of biliary tract infections
8. Patterns of disease recurrence
9. Locoregional control

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Medical Center Hamburg-Eppendorf

Sponsor organisation

University Medical Center Hamburg-Eppendorf

Address

Martinistrasse 52, Eppendorf Eppendorf

City

Hamburg

Postcode

20246

Country

Germany

Scientific contact point

Organisation

University Medical Center Hamburg-Eppendorf

Contact name

Prof. Dr. med. Henning Wege

Public contact point

Organisation

University Medical Center Hamburg-Eppendorf

Contact name

Prof. Dr. med. Henning Wege

Locations

4 EU/EEA countries · 29 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 21 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications