Acelarin First Line Randomised Pancreatic Study

Summary

The primary purpose of this study is to assess whether Acelarin (NUC-1031) is superior to gemcitabine in terms of overall survival for treatment of patients with metastatic pancreatic carcinoma. In addition disease progression, quality of life and comparative safety will be evaluated. Secondary objectives are to compare between the two treatment groups the following: * Progression Free Survival (PFS) * Radiological Response and disease control rate * Toxicity and safety * Quality of Life Additional, exploratory objectives are to discover and validate possible biomarkers to predict additional benefit of Acelarin (NUC-1031) over gemcitabine alone.

Timeline

Start

2015-12

Primary completion

2020-09

Completion

2022-12

Publications

• 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 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 Von Hoff DD, Ervin TJ, Arena FP, et al: "Randomized phase III study of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic adenocarcinoma of the pancreas (MPACT)". 2013 Gastrointestinal Cancers Symposium. J Clin Oncol 31, 2013 (suppl 4; abstract: LBA148)
• Background Ghazaly, E.A. et al. "ProGem1: Phase I first-in-human study of the novel nucleotide NUC-1031 in adult patients with advanced solid tumors" J Clin Oncol 31, 2013 (suppl; abstr 2576)
• Background de Sousa Cavalcante L, Monteiro G. Gemcitabine: metabolism and molecular mechanisms of action, sensitivity and chemoresistance in pancreatic cancer. Eur J Pharmacol. 2014 Oct 15;741:8-16. doi: 10.1016/j.ejphar.2014.07.041. Epub 2014 Jul 30.
• Background Achiwa H, Oguri T, Sato S, Maeda H, Niimi T, Ueda R. Determinants of sensitivity and resistance to gemcitabine: the roles of human equilibrative nucleoside transporter 1 and deoxycytidine kinase in non-small cell lung cancer. Cancer Sci. 2004 Sep;95(9):753-7. doi: 10.1111/j.1349-7006.2004.tb03257.x.
• Background Spratlin J, Sangha R, Glubrecht D, Dabbagh L, Young JD, Dumontet C, Cass C, Lai R, Mackey JR. The absence of human equilibrative nucleoside transporter 1 is associated with reduced survival in patients with gemcitabine-treated pancreas adenocarcinoma. Clin Cancer Res. 2004 Oct 15;10(20):6956-61. doi: 10.1158/1078-0432.CCR-04-0224.
• Background Ghazaly, E.A. et al. "ProGem1: A phase I/II study of a first-in-class nucleotide, Acelarin, in patients with advanced solid tumors" J Clin Oncol 32:5s, 2014 (suppl; abstr 2531)
• Background Sebastiani V, Ricci F, Rubio-Viqueira B, Kulesza P, Yeo CJ, Hidalgo M, Klein A, Laheru D, Iacobuzio-Donahue CA. Immunohistochemical and genetic evaluation of deoxycytidine kinase in pancreatic cancer: relationship to molecular mechanisms of gemcitabine resistance and survival. Clin Cancer Res. 2006 Apr 15;12(8):2492-7. doi: 10.1158/1078-0432.CCR-05-2655.
• Background Kroep JR, van Moorsel CJ, Veerman G, Voorn DA, Schultz RM, Worzalla JF, Tanzer LR, Merriman RL, Pinedo HM, Peters GJ. Role of deoxycytidine kinase (dCK), thymidine kinase 2 (TK2), and deoxycytidine deaminase (dCDA) in the antitumor activity of gemcitabine (dFdC). Adv Exp Med Biol. 1998;431:657-60. doi: 10.1007/978-1-4615-5381-6_127. No abstract available.
• Background Philip PA, Chansky K, LeBlanc M, Rubinstein L, Seymour L, Ivy SP, Alberts SR, Catalano PJ, Crowley J. Historical controls for metastatic pancreatic cancer: benchmarks for planning and analyzing single-arm phase II trials. Clin Cancer Res. 2014 Aug 15;20(16):4176-85. doi: 10.1158/1078-0432.CCR-13-2024. Epub 2014 Jun 9.
• Background Slusarczyk M, Lopez MH, Balzarini J, Mason M, Jiang WG, Blagden S, Thompson E, Ghazaly E, McGuigan C. Application of ProTide technology to gemcitabine: a successful approach to overcome the key cancer resistance mechanisms leads to a new agent (NUC-1031) in clinical development. J Med Chem. 2014 Feb 27;57(4):1531-42. doi: 10.1021/jm401853a. Epub 2014 Feb 14.
• Background Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W; National Cancer Institute of Canada Clinical Trials Group. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 May 20;25(15):1960-6. doi: 10.1200/JCO.2006.07.9525. Epub 2007 Apr 23.

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