Intrahepatic Cholangiocarcinoma Clinical Trial
Official title:
A Single-Arm Nonrandomized Phase II Study of Liver Transplantation in Locally Advanced Unresectable Non-Metastatic Intrahepatic Cholangiocarcinoma Treated With Neoadjuvant Systemic Therapy
The aim of the current study is to determine the potential efficacy of liver transplantation in the form of patients' overall survival (OS) after neoadjuvant systemic therapy in patients with biologically responsive locally advanced non-metastatic intrahepatic cholangiocarcinoma (iCCA) in comparison to patients historically treated with chemotherapy alone.
Status | Recruiting |
Enrollment | 30 |
Est. completion date | November 2029 |
Est. primary completion date | November 2028 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 89 Years |
Eligibility | Inclusion Criteria: - Age =18 years of age on the day of consenting to the study. - Patients must have histologically confirmed diagnosis of locally advanced intrahepatic cholangiocarcinoma - Confirmed diagnosis of locally advanced unresectable iCCA with no vascular invasion, lymph node, or extrahepatic disease. - Unresectable disease based on tumor location or underlying liver disease - Patients must have = 6 months of disease stability or tumor regression on neoadjuvant therapy. In cases in which patients had received second-line therapy, disease must also have been controlled for = 6 months on that regimen. - Patients who had previous surgical resection for iCCA are eligible if surgery occurred more than 6 months prior to listing, and patients have had = 6 months of disease stability or response on therapy. - ECOG performance status =1 (Karnofsky =70%, see Appendix A). - Patients must have organ and marrow function acceptable for liver transplantation per institutional protocol: - If history of chronic hepatitis B virus (HBV) infection, viral load should be undetectable on suppressive therapy. - If history of chronic hepatitis C virus (HCV) infection, patients should have undetectable HCV viral load. - Women of child-bearing years must have contraception plan in place from the time of study enrollment until at least one year following liver transplant. - Ability to understand and the willingness to sign a written informed consent document - Meets all other medical and psychosocial criteria for liver transplant - Demonstrate ability to comply with study procedures Exclusion Criteria: - Age <18 years of age on the day of consenting to the study. - Patients who have extrahepatic metastases, lymph node involvement, invasion or encasement of major hepatic vascular structures, perforation of the visceral peritoneum, invasion of extrahepatic structures, invasion of perihilar fat, periductular invasion, concurrent hepatoma or mixed hepatocellular cholangiocarcinoma. - Concurrent severe and/or uncontrolled concurrent illness including, but not limited to, ongoing or active infection, acute fulminant liver failure, symptomatic congestive heart failure, unstable angina pectoris, severe uncorrected coronary artery disease, severe cerebrovascular disease, severe pulmonary disease, or psychiatric illness/social situations that would limit compliance with study requirements and that would exclude the patient from eligibility for liver transplantation per institutional protocol. - Prior solid organ or bone marrow transplant - Dependent on =2 IV inotropic support to maintain hemodynamics - Previous (within the past 5 years) or concurrent presence of other cancer, except non-melanoma skin cancer and in situ carcinomas. - Eastern Cooperative Oncology Group (ECOG) Performance Status Scale score >1 (Karnofsky <70%, see Appendix A). - Unable to understand and sign a written informed consent document - Untreated viral hepatitis - Pregnant or breast-feeding women - HIV-infected patients |
Country | Name | City | State |
---|---|---|---|
United States | Rutgers New Jersey Medical School | Newark | New Jersey |
United States | University Hospital | Newark | New Jersey |
Lead Sponsor | Collaborator |
---|---|
Rutgers, The State University of New Jersey |
United States,
Banales JM, Cardinale V, Carpino G, Marzioni M, Andersen JB, Invernizzi P, Lind GE, Folseraas T, Forbes SJ, Fouassier L, Geier A, Calvisi DF, Mertens JC, Trauner M, Benedetti A, Maroni L, Vaquero J, Macias RI, Raggi C, Perugorria MJ, Gaudio E, Boberg KM, Marin JJ, Alvaro D. Expert consensus document: Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA). Nat Rev Gastroenterol Hepatol. 2016 May;13(5):261-80. doi: 10.1038/nrgastro.2016.51. Epub 2016 Apr 20. — View Citation
Becker NS, Rodriguez JA, Barshes NR, O'Mahony CA, Goss JA, Aloia TA. Outcomes analysis for 280 patients with cholangiocarcinoma treated with liver transplantation over an 18-year period. J Gastrointest Surg. 2008 Jan;12(1):117-22. doi: 10.1007/s11605-007-0335-4. Epub 2007 Oct 26. — View Citation
Benson AB 3rd, Abrams TA, Ben-Josef E, Bloomston PM, Botha JF, Clary BM, Covey A, Curley SA, D'Angelica MI, Davila R, Ensminger WD, Gibbs JF, Laheru D, Malafa MP, Marrero J, Meranze SG, Mulvihill SJ, Park JO, Posey JA, Sachdev J, Salem R, Sigurdson ER, Sofocleous C, Vauthey JN, Venook AP, Goff LW, Yen Y, Zhu AX. NCCN clinical practice guidelines in oncology: hepatobiliary cancers. J Natl Compr Canc Netw. 2009 Apr;7(4):350-91. doi: 10.6004/jnccn.2009.0027. No abstract available. — View Citation
Darwish Murad S, Kim WR, Harnois DM, Douglas DD, Burton J, Kulik LM, Botha JF, Mezrich JD, Chapman WC, Schwartz JJ, Hong JC, Emond JC, Jeon H, Rosen CB, Gores GJ, Heimbach JK. Efficacy of neoadjuvant chemoradiation, followed by liver transplantation, for perihilar cholangiocarcinoma at 12 US centers. Gastroenterology. 2012 Jul;143(1):88-98.e3; quiz e14. doi: 10.1053/j.gastro.2012.04.008. Epub 2012 Apr 12. — View Citation
De Martin E, Rayar M, Golse N, Dupeux M, Gelli M, Gnemmi V, Allard MA, Cherqui D, Sa Cunha A, Adam R, Coilly A, Antonini TM, Guettier C, Samuel D, Boudjema K, Boleslawski E, Vibert E. Analysis of Liver Resection Versus Liver Transplantation on Outcome of Small Intrahepatic Cholangiocarcinoma and Combined Hepatocellular-Cholangiocarcinoma in the Setting of Cirrhosis. Liver Transpl. 2020 Jun;26(6):785-798. doi: 10.1002/lt.25737. — View Citation
Doussot A, Gonen M, Wiggers JK, Groot-Koerkamp B, DeMatteo RP, Fuks D, Allen PJ, Farges O, Kingham TP, Regimbeau JM, D'Angelica MI, Azoulay D, Jarnagin WR. Recurrence Patterns and Disease-Free Survival after Resection of Intrahepatic Cholangiocarcinoma: Preoperative and Postoperative Prognostic Models. J Am Coll Surg. 2016 Sep;223(3):493-505.e2. doi: 10.1016/j.jamcollsurg.2016.05.019. Epub 2016 Jun 11. — View Citation
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026. — View Citation
Endo I, Gonen M, Yopp AC, Dalal KM, Zhou Q, Klimstra D, D'Angelica M, DeMatteo RP, Fong Y, Schwartz L, Kemeny N, O'Reilly E, Abou-Alfa GK, Shimada H, Blumgart LH, Jarnagin WR. Intrahepatic cholangiocarcinoma: rising frequency, improved survival, and determinants of outcome after resection. Ann Surg. 2008 Jul;248(1):84-96. doi: 10.1097/SLA.0b013e318176c4d3. — View Citation
Goldstein RM, Stone M, Tillery GW, Senzer N, Levy M, Husberg BS, Gonwa T, Klintmalm G. Is liver transplantation indicated for cholangiocarcinoma? Am J Surg. 1993 Dec;166(6):768-71; discussion 771-2. doi: 10.1016/s0002-9610(05)80696-8. — View Citation
Gupta R, Gupta J. Strategies to improve survival of patients with intrahepatic cholangiocarcinoma undergoing liver transplantation. Hepatology. 2017 May;65(5):1777-1778. doi: 10.1002/hep.28994. Epub 2017 Feb 3. No abstract available. — View Citation
Hong JC, Jones CM, Duffy JP, Petrowsky H, Farmer DG, French S, Finn R, Durazo FA, Saab S, Tong MJ, Hiatt JR, Busuttil RW. Comparative analysis of resection and liver transplantation for intrahepatic and hilar cholangiocarcinoma: a 24-year experience in a single center. Arch Surg. 2011 Jun;146(6):683-9. doi: 10.1001/archsurg.2011.116. — View Citation
Hong JC, Petrowsky H, Kaldas FM, Farmer DG, Durazo FA, Finn RS, Saab S, Han SH, Lee P, Markovic D, Lassman C, Hiatt JR, Busuttil RW. Predictive index for tumor recurrence after liver transplantation for locally advanced intrahepatic and hilar cholangiocarcinoma. J Am Coll Surg. 2011 Apr;212(4):514-20; discussion 520-1. doi: 10.1016/j.jamcollsurg.2010.12.005. — View Citation
Hyder O, Hatzaras I, Sotiropoulos GC, Paul A, Alexandrescu S, Marques H, Pulitano C, Barroso E, Clary BM, Aldrighetti L, Ferrone CR, Zhu AX, Bauer TW, Walters DM, Groeschl R, Gamblin TC, Marsh JW, Nguyen KT, Turley R, Popescu I, Hubert C, Meyer S, Choti MA, Gigot JF, Mentha G, Pawlik TM. Recurrence after operative management of intrahepatic cholangiocarcinoma. Surgery. 2013 Jun;153(6):811-8. doi: 10.1016/j.surg.2012.12.005. Epub 2013 Mar 15. — View Citation
Jain A, Javle M. Molecular profiling of biliary tract cancer: a target rich disease. J Gastrointest Oncol. 2016 Oct;7(5):797-803. doi: 10.21037/jgo.2016.09.01. — View Citation
Jain A, Kwong LN, Javle M. Genomic Profiling of Biliary Tract Cancers and Implications for Clinical Practice. Curr Treat Options Oncol. 2016 Nov;17(11):58. doi: 10.1007/s11864-016-0432-2. — View Citation
Javle M, Bekaii-Saab T, Jain A, Wang Y, Kelley RK, Wang K, Kang HC, Catenacci D, Ali S, Krishnan S, Ahn D, Bocobo AG, Zuo M, Kaseb A, Miller V, Stephens PJ, Meric-Bernstam F, Shroff R, Ross J. Biliary cancer: Utility of next-generation sequencing for clinical management. Cancer. 2016 Dec 15;122(24):3838-3847. doi: 10.1002/cncr.30254. Epub 2016 Sep 13. — View Citation
Lunsford KE, Javle M, Heyne K, Shroff RT, Abdel-Wahab R, Gupta N, Mobley CM, Saharia A, Victor DW, Nguyen DT, Graviss EA, Kaseb AO, McFadden RS, Aloia TA, Conrad C, Li XC, Monsour HP, Gaber AO, Vauthey JN, Ghobrial RM; Methodist-MD Anderson Joint Cholangi — View Citation
Marchan EM, Landry JC. Neoadjuvant chemoradiation followed by orthotopic liver transplantation in cholangiocarcinomas: the emory experience. J Gastrointest Oncol. 2016 Apr;7(2):248-54. doi: 10.3978/j.issn.2078-6891.2015.117. — View Citation
Meyer CG, Penn I, James L. Liver transplantation for cholangiocarcinoma: results in 207 patients. Transplantation. 2000 Apr 27;69(8):1633-7. doi: 10.1097/00007890-200004270-00019. — View Citation
Pichlmayr R, Weimann A, Oldhafer KJ, Schlitt HJ, Klempnauer J, Bornscheuer A, Chavan A, Schmoll E, Lang H, Tusch G, et al. Role of liver transplantation in the treatment of unresectable liver cancer. World J Surg. 1995 Nov-Dec;19(6):807-13. doi: 10.1007/BF00299775. — View Citation
Rana A, Hong JC. Orthotopic liver transplantation in combination with neoadjuvant therapy: a new paradigm in the treatment of unresectable intrahepatic cholangiocarcinoma. Curr Opin Gastroenterol. 2012 May;28(3):258-65. doi: 10.1097/MOG.0b013e32835168db. — View Citation
Rea DJ, Heimbach JK, Rosen CB, Haddock MG, Alberts SR, Kremers WK, Gores GJ, Nagorney DM. Liver transplantation with neoadjuvant chemoradiation is more effective than resection for hilar cholangiocarcinoma. Ann Surg. 2005 Sep;242(3):451-8; discussion 458-61. doi: 10.1097/01.sla.0000179678.13285.fa. — View Citation
Robles R, Figueras J, Turrion VS, Margarit C, Moya A, Varo E, Calleja J, Valdivieso A, Valdecasas JC, Lopez P, Gomez M, de Vicente E, Loinaz C, Santoyo J, Fleitas M, Bernardos A, Llado L, Ramirez P, Bueno FS, Jaurrieta E, Parrilla P. Spanish experience in liver transplantation for hilar and peripheral cholangiocarcinoma. Ann Surg. 2004 Feb;239(2):265-71. doi: 10.1097/01.sla.0000108702.45715.81. — View Citation
Sapisochin G, Facciuto M, Rubbia-Brandt L, Marti J, Mehta N, Yao FY, Vibert E, Cherqui D, Grant DR, Hernandez-Alejandro R, Dale CH, Cucchetti A, Pinna A, Hwang S, Lee SG, Agopian VG, Busuttil RW, Rizvi S, Heimbach JK, Montenovo M, Reyes J, Cesaretti M, Soubrane O, Reichman T, Seal J, Kim PT, Klintmalm G, Sposito C, Mazzaferro V, Dutkowski P, Clavien PA, Toso C, Majno P, Kneteman N, Saunders C, Bruix J; iCCA International Consortium. Liver transplantation for "very early" intrahepatic cholangiocarcinoma: International retrospective study supporting a prospective assessment. Hepatology. 2016 Oct;64(4):1178-88. doi: 10.1002/hep.28744. Epub 2016 Aug 24. — View Citation
Schule S, Altendorf-Hofmann A, Utess F, Rauchfuss F, Freesmeyer M, Knosel T, Dittmar Y, Settmacher U. Liver transplantation for hilar cholangiocarcinoma--a single-centre experience. Langenbecks Arch Surg. 2013 Jan;398(1):71-7. doi: 10.1007/s00423-012-1007-8. Epub 2012 Oct 9. — View Citation
Spolverato G, Kim Y, Ejaz A, Alexandrescu S, Marques H, Aldrighetti L, Gamblin TC, Pulitano C, Bauer TW, Shen F, Sandroussi C, Poultsides G, Maithel SK, Pawlik TM. Conditional Probability of Long-term Survival After Liver Resection for Intrahepatic Cholangiocarcinoma: A Multi-institutional Analysis of 535 Patients. JAMA Surg. 2015 Jun;150(6):538-45. doi: 10.1001/jamasurg.2015.0219. — View Citation
Sudan D, DeRoover A, Chinnakotla S, Fox I, Shaw B Jr, McCashland T, Sorrell M, Tempero M, Langnas A. Radiochemotherapy and transplantation allow long-term survival for nonresectable hilar cholangiocarcinoma. Am J Transplant. 2002 Sep;2(8):774-9. doi: 10.1034/j.1600-6143.2002.20812.x. — View Citation
Tabrizian P, Jibara G, Hechtman JF, Franssen B, Labow DM, Schwartz ME, Thung SN, Sarpel U. Outcomes following resection of intrahepatic cholangiocarcinoma. HPB (Oxford). 2015 Apr;17(4):344-51. doi: 10.1111/hpb.12359. Epub 2014 Nov 14. — View Citation
Wang Y, Li J, Xia Y, Gong R, Wang K, Yan Z, Wan X, Liu G, Wu D, Shi L, Lau W, Wu M, Shen F. Prognostic nomogram for intrahepatic cholangiocarcinoma after partial hepatectomy. J Clin Oncol. 2013 Mar 20;31(9):1188-95. doi: 10.1200/JCO.2012.41.5984. Epub 2013 Jan 28. — View Citation
* Note: There are 29 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 5-year Overall Survival Rate (ORS) | 5-year ORS is the length of time that patients diagnosed with locally advanced non-metastatic intrahepatic cholangiocarcinoma (iCCA) treated with neoadjuvant systemic therapy followed by liver transplant (LT) are still alive post-LT. | 5 years from the time of transplant or until death of patient, whichever came first | |
Secondary | Recurrence-free survival (RFS) | RFS is the length of time from liver transplantation (LT) to the time of disease recurrence, time of patient death, or time of study completion for patients with locally advanced non-metastatic intrahepatic cholangiocarcinoma treated with neoadjuvant systemic therapy followed by liver transplantation. | From date of transplant until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years | |
Secondary | Intent-to-treat Overall Survival Rate (ITT ORS) | ITT ORS is the length of time that patients diagnosed with locally advanced non-metastatic intrahepatic cholangiocarcinoma (iCCA) treated with neoadjuvant systemic therapy and waitlisted for liver transplant for iCCA are still alive after being waitlisted for liver transplantation. | 5 years from time of waitlist or until death of patient, whichever came first | |
Secondary | Post-liver transplant functional assessments to identify postoperative complications, short-term morbidities, and long-term morbidities | All serious adverse events will be followed and documented, including bleeding requiring re-operation, hepatic artery or portal vein thrombosis, bile duct leak, bile duct stricture, primary non-function of the transplant liver, need for re-transplant of the liver. | From date of emergence of a post-transplant adverse event until the date the adverse event is designated as resolved by investigator or its effect on patient's condition stabilizes, whichever came first, assessed up to 5 years |
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