Cholangiocarcinoma - null regimens

The purpose of this page is to provide references to "null therapy" such as placebo and observation. These references provide further insight into the historical development of the treatment landscape. See the main cholangiocarcinoma page for regimens that include active anticancer treatment.

Adjuvant therapy

Observation

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Primrose et al. 2019 (BILCAP)	2006-2014	Phase 3 (C)	Capecitabine	Did not meet primary endpoint of OS1 Median OS: 36.1 vs 49.6 mo (HR 1.19, 95% CI 0.94-1.49)
Ebata et al. 2018 (BCAT)	2007-2011	Phase 3 (C)	Gemcitabine	Did not meet primary endpoint of OS Median OS: 63.8 vs 62.3 mo (HR 0.99, 95% CI 0.69-1.43)
Edeline et al. 2019 (PRODIGE 12-ACCORD 18-UNICANCER GI)	2009-2014	Phase 3 (C)	GemOx	Did not meet primary endpoint of RFS Median RFS: 18.5 vs 30.4 mo (HR 1.14, 95% CI 0.80-1.61)

¹Reported efficacy is based on the 2022 update.
No antineoplastic treatment after surgery.

Preceding treatment

• Surgical resection with macroscopically curative resection

References

1. BCAT: Ebata T, Hirano S, Konishi M, Uesaka K, Tsuchiya Y, Ohtsuka M, Kaneoka Y, Yamamoto M, Ambo Y, Shimizu Y, Ozawa F, Fukutomi A, Ando M, Nimura Y, Nagino M; Bile Duct Cancer Adjuvant Trial (BCAT) Study Group. Randomized clinical trial of adjuvant gemcitabine chemotherapy versus observation in resected bile duct cancer. Br J Surg. 2018 Feb;105(3):192-202. link to original article PubMed UMIN000000820
2. PRODIGE 12-ACCORD 18-UNICANCER GI: Edeline J, Benabdelghani M, Bertaut A, Watelet J, Hammel P, Joly JP, Boudjema K, Fartoux L, Bouhier-Leporrier K, Jouve JL, Faroux R, Guerin-Meyer V, Kurtz JE, Assénat E, Seitz JF, Baumgaertner I, Tougeron D, de la Fouchardière C, Lombard-Bohas C, Boucher E, Stanbury T, Louvet C, Malka D, Phelip JM. Gemcitabine and Oxaliplatin Chemotherapy or Surveillance in Resected Biliary Tract Cancer (PRODIGE 12-ACCORD 18-UNICANCER GI): A Randomized Phase III Study. J Clin Oncol. 2019 Mar 10;37(8):658-667. Epub 2019 Feb 1. link to original article PubMed NCT01313377
3. BILCAP: Primrose JN, Fox RP, Palmer DH, Malik HZ, Prasad R, Mirza D, Anthoney A, Corrie P, Falk S, Finch-Jones M, Wasan H, Ross P, Wall L, Wadsley J, Evans JTR, Stocken D, Praseedom R, Ma YT, Davidson B, Neoptolemos JP, Iveson T, Raftery J, Zhu S, Cunningham D, Garden OJ, Stubbs C, Valle JW, Bridgewater J; BILCAP study group. Capecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study. Lancet Oncol. 2019 May;20(5):663-673. Epub 2019 Mar 25. Erratum in: Lancet Oncol. 2019 Apr 2. link to original article PubMed NCT00363584
   1. Update: Bridgewater J, Fletcher P, Palmer DH, Malik HZ, Prasad R, Mirza D, Anthoney A, Corrie P, Falk S, Finch-Jones M, Wasan H, Ross P, Wall L, Wadsley J, Evans TR, Stocken D, Stubbs C, Praseedom R, Ma YT, Davidson B, Neoptolemos J, Iveson T, Cunningham D, Garden OJ, Valle JW, Primrose J; BILCAP study group. Long-Term Outcomes and Exploratory Analyses of the Randomized Phase III BILCAP Study. J Clin Oncol. 2022 Jun 20;40(18):2048-2057. Epub 2022 Mar 22. link to original article PubMed

Metastatic disease, all lines of therapy

Best supportive care

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Glimelius et al. 1996	1991-1995	Phase 3 (C)	1a. FELV 1b. FULV	Inferior OS
Lamarca et al. 2021 (ABC-06)	2014-2018	Phase 3 (C)	1a. mFOLFOX6 1b. mFOLFOX6 (L-Leucovorin)	Seems to have inferior OS

No antineoplastic treatment.

References

1. Glimelius B, Hoffman K, Sjödén PO, Jacobsson G, Sellström H, Enander LK, Linné T, Svensson C. Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Ann Oncol. 1996 Aug;7(6):593-600. link to original article PubMed content property of HemOnc.org
2. ABC-06: Lamarca A, Palmer DH, Wasan HS, Ross PJ, Ma YT, Arora A, Falk S, Gillmore R, Wadsley J, Patel K, Anthoney A, Maraveyas A, Iveson T, Waters JS, Hobbs C, Barber S, Ryder WD, Ramage J, Davies LM, Bridgewater JA, Valle JW; Advanced Biliary Cancer Working Group. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2021 May;22(5):690-701. Epub 2021 Mar 30. link to original article link to PMC article PubMed NCT01926236

Placebo

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Abou-Alfa et al. 2020 (ClarIDHy)	2017-2019	Phase 3 (C)	Ivosidenib	Inferior PFS

No active antineoplastic treatment.

Biomarker eligibility criteria

• IDH1 mutation

References

1. ClarIDHy: Abou-Alfa GK, Macarulla T, Javle MM, Kelley RK, Lubner SJ, Adeva J, Cleary JM, Catenacci DV, Borad MJ, Bridgewater J, Harris WP, Murphy AG, Oh DY, Whisenant J, Lowery MA, Goyal L, Shroff RT, El-Khoueiry AB, Fan B, Wu B, Chamberlain CX, Jiang L, Gliser C, Pandya SS, Valle JW, Zhu AX. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Jun;21(6):796-807. Epub 2020 May 13. Erratum in: Lancet Oncol. 2020 Oct;21(10):e462. link to original article link to PMC article PubMed NCT02989857