Study protocol of an open-label, single arm phase II trial investigating the efficacy and safety of Trifluridine/Tipiracil combined with irinotecan as a second line therapy in patients with cholangiocarcinoma (TRITICC).
Adult
Humans
Irinotecan
Prospective Studies
Trifluridine
/ adverse effects
Frontotemporal Dementia
/ chemically induced
Gemcitabine
Cholangiocarcinoma
/ drug therapy
Biliary Tract Neoplasms
/ drug therapy
Deoxycytidine
Cisplatin
Bile Duct Neoplasms
/ drug therapy
Bile Ducts, Intrahepatic
/ pathology
Disease Progression
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Colorectal Neoplasms
/ pathology
Clinical Trials, Phase II as Topic
Biliary tract cancer
Chemotherapy
Cholangiocarcinoma
FTD/TPI (Trifluridine/Tipiracil)
Gall bladder carcinoma
Irinotecan
Second-line treatment
Translational research
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
22 May 2023
22 May 2023
Historique:
received:
06
03
2022
accepted:
16
05
2023
medline:
24
5
2023
pubmed:
23
5
2023
entrez:
22
5
2023
Statut:
epublish
Résumé
The prognosis of patients with advanced biliary tract cancer (BTC) who have progressed on gemcitabine plus cisplatin is dismal. Trifluridine/tipiracil (FTD/TPI) and irinotecan have proven efficacy in different gastrointestinal malignancies. We therefore hypothesized that this combination might improve the therapeutic outcome in patients with BTC after failure of first line treatment. TRITICC is an interventional, prospective, open-label, non-randomised, exploratory, multicentre, single-arm phase IIA clinical trial done in 6 sites with expertise in managing biliary tract cancer across Germany. A total of 28 adult patients (aged ≥ 18 years) with histologically verified locally advanced or metastatic biliary tract cancer (including cholangiocarcinoma and gallbladder or ampullary carcinoma) with documented radiological disease progression to first-line gemcitabine based chemotherapy will be included to receive a combination of FTD/TPI plus irinotecan according to previously published protocols. Study treatment will be continued until disease progression according to RECIST 1.1 criteria or occurrence of unacceptable toxicity. The effect of FTD/TPI plus irinotecan on progression-free survival will be analyzed as primary endpoint. Safety (according to NCI-CTCAE), response rates and overall survival are secondary endpoints. In addition, a comprehensive translational research program is part of the study and might provide findings about predictive markers with regard to response, survival periods and resistance to treatment. The aim of TRITICC is to evaluate the safety and efficacy of FTD/TPI plus irinotecan in patients with biliary tract cancer refractory to previous Gemcitabine based treatment. EudraCT 2018-002936-26; NCT04059562.
Sections du résumé
BACKGROUND
BACKGROUND
The prognosis of patients with advanced biliary tract cancer (BTC) who have progressed on gemcitabine plus cisplatin is dismal. Trifluridine/tipiracil (FTD/TPI) and irinotecan have proven efficacy in different gastrointestinal malignancies. We therefore hypothesized that this combination might improve the therapeutic outcome in patients with BTC after failure of first line treatment.
METHODS
METHODS
TRITICC is an interventional, prospective, open-label, non-randomised, exploratory, multicentre, single-arm phase IIA clinical trial done in 6 sites with expertise in managing biliary tract cancer across Germany. A total of 28 adult patients (aged ≥ 18 years) with histologically verified locally advanced or metastatic biliary tract cancer (including cholangiocarcinoma and gallbladder or ampullary carcinoma) with documented radiological disease progression to first-line gemcitabine based chemotherapy will be included to receive a combination of FTD/TPI plus irinotecan according to previously published protocols. Study treatment will be continued until disease progression according to RECIST 1.1 criteria or occurrence of unacceptable toxicity. The effect of FTD/TPI plus irinotecan on progression-free survival will be analyzed as primary endpoint. Safety (according to NCI-CTCAE), response rates and overall survival are secondary endpoints. In addition, a comprehensive translational research program is part of the study and might provide findings about predictive markers with regard to response, survival periods and resistance to treatment.
DISCUSSION
CONCLUSIONS
The aim of TRITICC is to evaluate the safety and efficacy of FTD/TPI plus irinotecan in patients with biliary tract cancer refractory to previous Gemcitabine based treatment.
TRIAL REGISTRATION
BACKGROUND
EudraCT 2018-002936-26; NCT04059562.
Identifiants
pubmed: 37217885
doi: 10.1186/s12885-023-10972-6
pii: 10.1186/s12885-023-10972-6
pmc: PMC10204189
doi:
Substances chimiques
Irinotecan
7673326042
tipiracil
NGO10K751P
Trifluridine
RMW9V5RW38
Gemcitabine
0
Deoxycytidine
0W860991D6
Cisplatin
Q20Q21Q62J
Banques de données
ClinicalTrials.gov
['NCT04059562']
Types de publication
Clinical Trial
Clinical Trial Protocol
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
470Informations de copyright
© 2023. The Author(s).
Références
Eur J Cancer. 2009 Jan;45(2):228-47
pubmed: 19097774
Cancer. 2015 Sep 15;121(18):3290-7
pubmed: 26052689
Nat Rev Gastroenterol Hepatol. 2020 Sep;17(9):557-588
pubmed: 32606456
Stat Med. 1998 Apr 30;17(8):857-72
pubmed: 9595616
Eur J Cancer. 1998 Aug;34(9):1381-9
pubmed: 9849421
Ann Oncol. 2014 Dec;25(12):2328-2338
pubmed: 24769639
Eur J Cancer. 2017 Aug;81:174-182
pubmed: 28633088
Best Pract Res Clin Gastroenterol. 2015 Apr;29(2):245-52
pubmed: 25966425
N Engl J Med. 2010 Apr 8;362(14):1273-81
pubmed: 20375404
Best Pract Res Clin Gastroenterol. 2015 Apr;29(2):221-32
pubmed: 25966423
Eur J Cancer. 2001 Jul;37(11):1345-51
pubmed: 11435063
Lancet Oncol. 2018 Nov;19(11):1437-1448
pubmed: 30355453
Anticancer Res. 2013 Jun;33(6):2619-22
pubmed: 23749917
World J Gastroenterol. 2015 Feb 21;21(7):2096-101
pubmed: 25717243
J Natl Cancer Inst. 1993 Mar 3;85(5):365-76
pubmed: 8433390
Br J Cancer. 2010 Aug 10;103(4):469-74
pubmed: 20628385
Invest New Drugs. 2015 Oct;33(5):1068-77
pubmed: 26163340
Oncologist. 2020 May;25(5):380-e763
pubmed: 31826977
Expert Rev Gastroenterol Hepatol. 2010 Aug;4(4):395-7
pubmed: 20678012
Lancet. 2016 Feb 6;387(10018):545-557
pubmed: 26615328
ESMO Open. 2020 Aug;4(Suppl 2):e000813
pubmed: 32817137
Clin Cancer Res. 2020 Apr 1;26(7):1555-1562
pubmed: 31924737
Anticancer Drugs. 2013 Oct;24(9):980-5
pubmed: 23928570
ESMO Open. 2022 Feb;7(1):100378
pubmed: 35032765
Health Qual Life Outcomes. 2011 Aug 22;9:70
pubmed: 21859485
Drugs. 2016 Sep;76(14):1393-402
pubmed: 27568360
Am J Clin Oncol. 2007 Jun;30(3):319-24
pubmed: 17551313
Eur J Cancer. 2013 Jan;49(2):329-35
pubmed: 22947649
Qual Life Res. 1996 Dec;5(6):555-67
pubmed: 8993101
Cancer Treat Rev. 2015 Nov;41(9):777-83
pubmed: 26428513
Future Oncol. 2016 Jan;12(2):153-63
pubmed: 26616466
Eur J Cancer. 2021 Sep;154:288-295
pubmed: 34303267
Lancet Oncol. 2021 May;22(5):690-701
pubmed: 33798493
Pharmacoeconomics. 2007;25(5):365-84
pubmed: 17488136
Lancet Oncol. 2021 Nov;22(11):1560-1572
pubmed: 34656226
N Engl J Med. 2015 May 14;372(20):1909-19
pubmed: 25970050
Int J Mol Med. 2004 Apr;13(4):545-9
pubmed: 15010854