Study of Tamoxifen in Well Differentiated Neuroendocrine Tumors and Hormone Receptor Positive Expression

Summary

This is a single-arm, unicentric, single-stage clinical study of tamoxifen for patients with well differentiated neuroendocrine tumors and radiological progression with positive (\> 1 percent) HR (estrogen and / or progesterone) expression by IHC. It will evaluate if Tamoxifen exerts antitumor action in patients with well differentiated NET and positive for the expression of HR, estrogen and / or progesterone.

Timeline

Start

2019-03-13

Primary completion

2023-05-13

Completion

2023-05-13

Publications

• Background Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, Abdalla EK, Fleming JB, Vauthey JN, Rashid A, Evans DB. One hundred years after "carcinoid": epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008 Jun 20;26(18):3063-72. doi: 10.1200/JCO.2007.15.4377.
• Background Caplin ME, Buscombe JR, Hilson AJ, Jones AL, Watkinson AF, Burroughs AK. Carcinoid tumour. Lancet. 1998 Sep 5;352(9130):799-805. doi: 10.1016/S0140-6736(98)02286-7.
• Background Modlin IM, Pavel M, Kidd M, Gustafsson BI. Review article: somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine (carcinoid) tumours. Aliment Pharmacol Ther. 2010 Jan 15;31(2):169-88. doi: 10.1111/j.1365-2036.2009.04174.x. Epub 2009 Oct 21.
• Background Caplin ME, Pavel M, Ruszniewski P. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med. 2014 Oct 16;371(16):1556-7. doi: 10.1056/NEJMc1409757. No abstract available.
• Background Rinke A, Muller HH, Schade-Brittinger C, Klose KJ, Barth P, Wied M, Mayer C, Aminossadati B, Pape UF, Blaker M, Harder J, Arnold C, Gress T, Arnold R; PROMID Study Group. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol. 2009 Oct 1;27(28):4656-63. doi: 10.1200/JCO.2009.22.8510. Epub 2009 Aug 24.
• Background Viale G, Doglioni C, Gambacorta M, Zamboni G, Coggi G, Bordi C. Progesterone receptor immunoreactivity in pancreatic endocrine tumors. An immunocytochemical study of 156 neuroendocrine tumors of the pancreas, gastrointestinal and respiratory tracts, and skin. Cancer. 1992 Nov 1;70(9):2268-77. doi: 10.1002/1097-0142(19921101)70:93.0.co;2-x.
• Background Zimmermann N, Lazar-Karsten P, Keck T, Billmann F, Schmid S, Brabant G, Thorns C. Expression Pattern of CDX2, Estrogen and Progesterone Receptors in Primary Gastroenteropancreatic Neuroendocrine Tumors and Metastases. Anticancer Res. 2016 Mar;36(3):921-4.
• Background Estrella JS, Broaddus RR, Mathews A, Milton DR, Yao JC, Wang H, Rashid A. Progesterone receptor and PTEN expression predict survival in patients with low- and intermediate-grade pancreatic neuroendocrine tumors. Arch Pathol Lab Med. 2014 Aug;138(8):1027-36. doi: 10.5858/arpa.2013-0195-OA.
• Background Kim SJ, An S, Lee JH, Kim JY, Song KB, Hwang DW, Kim SC, Yu E, Hong SM. Loss of Progesterone Receptor Expression Is an Early Tumorigenesis Event Associated with Tumor Progression and Shorter Survival in Pancreatic Neuroendocrine Tumor Patients. J Pathol Transl Med. 2017 Jul;51(4):388-395. doi: 10.4132/jptm.2017.03.19. Epub 2017 Jun 8.
• Background Arganini M, Spinelli C, Cecchini GM, Miccoli P. Long term treatment with tamoxifen for metastatic carcinoid tumor. Acta Chir Belg. 1989 Jul-Aug;89(4):209-11.
• Background Myers CF, Ershler WB, Tannenbaum MA, Barth R. Tamoxifen and carcinoid tumor. Ann Intern Med. 1982 Mar;96(3):383. doi: 10.7326/0003-4819-96-3-383_1. No abstract available.
• Background Biasco E, Antonuzzo A, Galli L, Baldi GG, Derosa L, Marconcini R, Farnesi A, Ricci S, Falcone A. Small-bowel neuroendocrine tumor and retroperitoneal fibrosis: efficacy of octreotide and tamoxifen. Tumori. 2015 Mar 20;101(1):e24-8. doi: 10.5301/tj.5000259.
• Background Stathopoulos GP, Karvountzis GG, Yiotis J. Tamoxifen in carcinoid syndrome. N Engl J Med. 1981 Jul 2;305(1):52. doi: 10.1056/NEJM198107023050115. No abstract available.
• Background Moertel CG, Engstrom PF, Schutt AJ. Tamoxifen therapy for metastatic carcinoid tumor: a negative study. Ann Intern Med. 1984 Apr;100(4):531-2. doi: 10.7326/0003-4819-100-4-531. No abstract available.
• Background Harvey JM, Clark GM, Osborne CK, Allred DC. Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol. 1999 May;17(5):1474-81. doi: 10.1200/JCO.1999.17.5.1474.
• Background Goldhirsch A, Glick JH, Gelber RD, Coates AS, Thurlimann B, Senn HJ; Panel members. Meeting highlights: international expert consensus on the primary therapy of early breast cancer 2005. Ann Oncol. 2005 Oct;16(10):1569-83. doi: 10.1093/annonc/mdi326. Epub 2005 Sep 7.
• Background Krebs MG, Hou JM, Sloane R, Lancashire L, Priest L, Nonaka D, Ward TH, Backen A, Clack G, Hughes A, Ranson M, Blackhall FH, Dive C. Analysis of circulating tumor cells in patients with non-small cell lung cancer using epithelial marker-dependent and -independent approaches. J Thorac Oncol. 2012 Feb;7(2):306-15. doi: 10.1097/JTO.0b013e31823c5c16.
• Background Crippa S, Partelli S, Belfiori G, Palucci M, Muffatti F, Adamenko O, Cardinali L, Doglioni C, Zamboni G, Falconi M. Management of neuroendocrine carcinomas of the pancreas (WHO G3): A tailored approach between proliferation and morphology. World J Gastroenterol. 2016 Dec 7;22(45):9944-9953. doi: 10.3748/wjg.v22.i45.9944.
• Background Furr BJ, Jordan VC. The pharmacology and clinical uses of tamoxifen. Pharmacol Ther. 1984;25(2):127-205. doi: 10.1016/0163-7258(84)90043-3. No abstract available.
• Background Shiau AK, Barstad D, Loria PM, Cheng L, Kushner PJ, Agard DA, Greene GL. The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen. Cell. 1998 Dec 23;95(7):927-37. doi: 10.1016/s0092-8674(00)81717-1.
• Background Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, Van Cutsem E, Hobday TJ, Okusaka T, Capdevila J, de Vries EG, Tomassetti P, Pavel ME, Hoosen S, Haas T, Lincy J, Lebwohl D, Oberg K; RAD001 in Advanced Neuroendocrine Tumors, Third Trial (RADIANT-3) Study Group. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011 Feb 10;364(6):514-23. doi: 10.1056/NEJMoa1009290.
• Barros MJ, Strosberg J, Al-Toubah T, de Jesus VHF, Durant L, Mello CA, Felismino TC, De Brot L, Taboada RG, Donadio MD, Riechelmann RP. HORMONET: a phase II trial of tamoxifen for estrogen/progesterone receptor-positive neuroendocrine tumors. Ther Adv Med Oncol. 2023 Jul 29;15:17588359231186041. doi: 10.1177/17588359231186041. eCollection 2023.

Drugs

Indications