Sintilimab Combined With Chemotherapy and Radiotherapy in Patients With Inoperable Pancreatic Cancer

Summary

Hypothesis: Survival benefits could be found in Sintilimab plus chemotherapy and radiotherapy in patients with inoperable pancreatic cancer.

Timeline

Start

2023-08-18

Primary completion

2025-08-18

Completion

2026-08-18

Publications

• Background Ilic M, Ilic I. Epidemiology of pancreatic cancer. World J Gastroenterol. 2016 Nov 28;22(44):9694-9705. doi: 10.3748/wjg.v22.i44.9694.
• Background Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014 Jun 1;74(11):2913-21. doi: 10.1158/0008-5472.CAN-14-0155.
• Background Strohl MP, Raigani S, Ammori JB, Hardacre JM, Kim JA. Surgery for Localized Pancreatic Cancer: The Trend Is Not Improving. Pancreas. 2016 May-Jun;45(5):687-93. doi: 10.1097/MPA.0000000000000511.
• Background Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardiere C, Bennouna J, Bachet JB, Khemissa-Akouz F, Pere-Verge D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M; Groupe Tumeurs Digestives of Unicancer; PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011 May 12;364(19):1817-25. doi: 10.1056/NEJMoa1011923.
• Background Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997 Jun;15(6):2403-13. doi: 10.1200/JCO.1997.15.6.2403.
• Background Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703. doi: 10.1056/NEJMoa1304369. Epub 2013 Oct 16.
• Background Fukumura D, Jain RK. Tumor microvasculature and microenvironment: targets for anti-angiogenesis and normalization. Microvasc Res. 2007 Sep-Nov;74(2-3):72-84. doi: 10.1016/j.mvr.2007.05.003. Epub 2007 May 18.
• Background Badiyan SN, Molitoris JK, Chuong MD, Regine WF, Kaiser A. The Role of Radiation Therapy for Pancreatic Cancer in the Adjuvant and Neoadjuvant Settings. Surg Oncol Clin N Am. 2017 Jul;26(3):431-453. doi: 10.1016/j.soc.2017.01.012. Epub 2017 May 11.
• Background Auclin E, Marthey L, Abdallah R, Mas L, Francois E, Saint A, Cunha AS, Vienot A, Lecomte T, Hautefeuille V, de La Fouchardiere C, Sarabi M, Ksontini F, Forestier J, Coriat R, Fabiano E, Leroy F, Williet N, Bachet JB, Tougeron D, Taieb J. Role of FOLFIRINOX and chemoradiotherapy in locally advanced and borderline resectable pancreatic adenocarcinoma: update of the AGEO cohort. Br J Cancer. 2021 Jun;124(12):1941-1948. doi: 10.1038/s41416-021-01341-w. Epub 2021 Mar 26.
• Background Loehrer PJ Sr, Feng Y, Cardenes H, Wagner L, Brell JM, Cella D, Flynn P, Ramanathan RK, Crane CH, Alberts SR, Benson AB 3rd. Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2011 Nov 1;29(31):4105-12. doi: 10.1200/JCO.2011.34.8904. Epub 2011 Oct 3.
• Background Chauffert B, Mornex F, Bonnetain F, Rougier P, Mariette C, Bouche O, Bosset JF, Aparicio T, Mineur L, Azzedine A, Hammel P, Butel J, Stremsdoerfer N, Maingon P, Bedenne L. Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000-01 FFCD/SFRO study. Ann Oncol. 2008 Sep;19(9):1592-9. doi: 10.1093/annonc/mdn281. Epub 2008 May 7.
• Background Hammel P, Huguet F, van Laethem JL, Goldstein D, Glimelius B, Artru P, Borbath I, Bouche O, Shannon J, Andre T, Mineur L, Chibaudel B, Bonnetain F, Louvet C; LAP07 Trial Group. Effect of Chemoradiotherapy vs Chemotherapy on Survival in Patients With Locally Advanced Pancreatic Cancer Controlled After 4 Months of Gemcitabine With or Without Erlotinib: The LAP07 Randomized Clinical Trial. JAMA. 2016 May 3;315(17):1844-53. doi: 10.1001/jama.2016.4324.
• Background Radiation therapy combined with Adriamycin or 5-fluorouracil for the treatment of locally unresectable pancreatic carcinoma. Gastrointestinal Tumor Study Group. Cancer. 1985 Dec 1;56(11):2563-8. doi: 10.1002/1097-0142(19851201)56:113.0.co;2-0.
• Background de Geus SWL, Eskander MF, Kasumova GG, Ng SC, Kent TS, Mancias JD, Callery MP, Mahadevan A, Tseng JF. Stereotactic body radiotherapy for unresected pancreatic cancer: A nationwide review. Cancer. 2017 Nov 1;123(21):4158-4167. doi: 10.1002/cncr.30856. Epub 2017 Jul 14.
• Background Tchelebi LT, Lehrer EJ, Trifiletti DM, Sharma NK, Gusani NJ, Crane CH, Zaorsky NG. Conventionally fractionated radiation therapy versus stereotactic body radiation therapy for locally advanced pancreatic cancer (CRiSP): An international systematic review and meta-analysis. Cancer. 2020 May 15;126(10):2120-2131. doi: 10.1002/cncr.32756. Epub 2020 Mar 3.
• Background Hewitt DB, Nissen N, Hatoum H, Musher B, Seng J, Coveler AL, Al-Rajabi R, Yeo CJ, Leiby B, Banks J, Balducci L, Vaccaro G, LoConte N, George TJ, Brenner W, Elquza E, Vahanian N, Rossi G, Kennedy E, Link C, Lavu H. A Phase 3 Randomized Clinical Trial of Chemotherapy With or Without Algenpantucel-L (HyperAcute-Pancreas) Immunotherapy in Subjects With Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer. Ann Surg. 2022 Jan 1;275(1):45-53. doi: 10.1097/SLA.0000000000004669.
• Background Ahmad G, Mackenzie GG, Egan J, Amiji MM. DHA-SBT-1214 Taxoid Nanoemulsion and Anti-PD-L1 Antibody Combination Therapy Enhances Antitumor Efficacy in a Syngeneic Pancreatic Adenocarcinoma Model. Mol Cancer Ther. 2019 Nov;18(11):1961-1972. doi: 10.1158/1535-7163.MCT-18-1046. Epub 2019 Aug 22.
• Background Weiss GJ, Blaydorn L, Beck J, Bornemann-Kolatzki K, Urnovitz H, Schutz E, Khemka V. Phase Ib/II study of gemcitabine, nab-paclitaxel, and pembrolizumab in metastatic pancreatic adenocarcinoma. Invest New Drugs. 2018 Feb;36(1):96-102. doi: 10.1007/s10637-017-0525-1. Epub 2017 Nov 8.
• Background Padron LJ, Maurer DM, O'Hara MH, O'Reilly EM, Wolff RA, Wainberg ZA, Ko AH, Fisher G, Rahma O, Lyman JP, Cabanski CR, Yu JX, Pfeiffer SM, Spasic M, Xu J, Gherardini PF, Karakunnel J, Mick R, Alanio C, Byrne KT, Hollmann TJ, Moore JS, Jones DD, Tognetti M, Chen RO, Yang X, Salvador L, Wherry EJ, Dugan U, O'Donnell-Tormey J, Butterfield LH, Hubbard-Lucey VM, Ibrahim R, Fairchild J, Bucktrout S, LaVallee TM, Vonderheide RH. Sotigalimab and/or nivolumab with chemotherapy in first-line metastatic pancreatic cancer: clinical and immunologic analyses from the randomized phase 2 PRINCE trial. Nat Med. 2022 Jun;28(6):1167-1177. doi: 10.1038/s41591-022-01829-9. Epub 2022 Jun 3.
• Results Zhong J, Patel K, Switchenko J, Cassidy RJ, Hall WA, Gillespie T, Patel PR, Kooby D, Landry J. Outcomes for patients with locally advanced pancreatic adenocarcinoma treated with stereotactic body radiation therapy versus conventionally fractionated radiation. Cancer. 2017 Sep 15;123(18):3486-3493. doi: 10.1002/cncr.30706. Epub 2017 May 10.
• Results Chen IM, Donia M, Chamberlain CA, Jensen AWP, Draghi A, Theile S, Madsen K, Hasselby JP, Toxvaerd A, Hogdall E, Lorentzen T, Wilken EE, Geertsen P, Svane IM, Johansen JS, Nielsen D. Phase 2 study of ipilimumab, nivolumab, and tocilizumab combined with stereotactic body radiotherapy in patients with refractory pancreatic cancer (TRIPLE-R). Eur J Cancer. 2023 Feb;180:125-133. doi: 10.1016/j.ejca.2022.11.035. Epub 2022 Dec 10.
• Results Zhu X, Cao Y, Liu W, Ju X, Zhao X, Jiang L, Ye Y, Jin G, Zhang H. Stereotactic body radiotherapy plus pembrolizumab and trametinib versus stereotactic body radiotherapy plus gemcitabine for locally recurrent pancreatic cancer after surgical resection: an open-label, randomised, controlled, phase 2 trial. Lancet Oncol. 2021 Aug;22(8):1093-1102. doi: 10.1016/S1470-2045(21)00286-2. Epub 2021 Jul 5.
• Results Chen IM, Johansen JS, Theile S, Hjaltelin JX, Novitski SI, Brunak S, Hasselby JP, Willemoe GL, Lorentzen T, Madsen K, Jensen BV, Wilken EE, Geertsen P, Behrens C, Nolsoe C, Hermann KL, Svane IM, Nielsen D. Randomized Phase II Study of Nivolumab With or Without Ipilimumab Combined With Stereotactic Body Radiotherapy for Refractory Metastatic Pancreatic Cancer (CheckPAC). J Clin Oncol. 2022 Sep 20;40(27):3180-3189. doi: 10.1200/JCO.21.02511. Epub 2022 Apr 27.

Drugs

Indications