Efficacy of metfOrmin in PrevenTIng Glucocorticoid-induced Diabetes in Patients With Brain Metastases

Summary

This is a monocentric, open label, randomized Phase II study in patients with brain metastasis from melanoma, lung or breast cancer, who require treatment with high-dose dexamethasone, as defined as a minimum of 8 mg daily based on the clinician judgment, for at least three weeks, with or without radiation therapy. The aim is to investigate the metformin efficacy in preventing the onset of glucocorticoid-induced diabetes and other metabolic perturbations in patients with brain metastases from melanoma, lung or breast cancer.

Timeline

Start

2019-10-15

Primary completion

2021-12-31

Completion

2022-03-31

Publications

• Background Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011 Mar 4;144(5):646-74. doi: 10.1016/j.cell.2011.02.013.
• Background Vernieri C, Casola S, Foiani M, Pietrantonio F, de Braud F, Longo V. Targeting Cancer Metabolism: Dietary and Pharmacologic Interventions. Cancer Discov. 2016 Dec;6(12):1315-1333. doi: 10.1158/2159-8290.CD-16-0615. Epub 2016 Nov 21.
• Background O'Neill LA, Kishton RJ, Rathmell J. A guide to immunometabolism for immunologists. Nat Rev Immunol. 2016 Sep;16(9):553-65. doi: 10.1038/nri.2016.70. Epub 2016 Jul 11.
• Background Lin X, DeAngelis LM. Treatment of Brain Metastases. J Clin Oncol. 2015 Oct 20;33(30):3475-84. doi: 10.1200/JCO.2015.60.9503. Epub 2015 Aug 17.
• Background Harris D, Barts A, Connors J, Dahl M, Elliott T, Kong J, Keane T, Thompson D, Stafford S, Ur E, Sirrs S. Glucocorticoid-induced hyperglycemia is prevalent and unpredictable for patients undergoing cancer therapy: an observational cohort study. Curr Oncol. 2013 Dec;20(6):e532-8. doi: 10.3747/co.20.1499.
• Background Weiser MA, Cabanillas ME, Konopleva M, Thomas DA, Pierce SA, Escalante CP, Kantarjian HM, O'Brien SM. Relation between the duration of remission and hyperglycemia during induction chemotherapy for acute lymphocytic leukemia with a hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone/methotrexate-cytarabine regimen. Cancer. 2004 Mar 15;100(6):1179-85. doi: 10.1002/cncr.20071.
• Background Furnary AP, Gao G, Grunkemeier GL, Wu Y, Zerr KJ, Bookin SO, Floten HS, Starr A. Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2003 May;125(5):1007-21. doi: 10.1067/mtc.2003.181.
• Background Perez A, Jansen-Chaparro S, Saigi I, Bernal-Lopez MR, Minambres I, Gomez-Huelgas R. Glucocorticoid-induced hyperglycemia. J Diabetes. 2014 Jan;6(1):9-20. doi: 10.1111/1753-0407.12090. Epub 2013 Oct 29.
• Background Oyer DS, Shah A, Bettenhausen S. How to manage steroid diabetes in the patient with cancer. J Support Oncol. 2006 Oct;4(9):479-83. No abstract available.
• Background Bozzi F, Mogavero A, Varinelli L, Belfiore A, Manenti G, Caccia C, Volpi CC, Beznoussenko GV, Milione M, Leoni V, Gloghini A, Mironov AA, Leo E, Pilotti S, Pierotti MA, Bongarzone I, Gariboldi M. MIF/CD74 axis is a target for novel therapies in colon carcinomatosis. J Exp Clin Cancer Res. 2017 Jan 23;36(1):16. doi: 10.1186/s13046-016-0475-z.
• Background Wallace MD, Metzger NL. Optimizing the Treatment of Steroid-Induced Hyperglycemia. Ann Pharmacother. 2018 Jan;52(1):86-90. doi: 10.1177/1060028017728297. Epub 2017 Aug 24.
• Background Kwon S, Hermayer KL, Hermayer K. Glucocorticoid-induced hyperglycemia. Am J Med Sci. 2013 Apr;345(4):274-277. doi: 10.1097/MAJ.0b013e31828a6a01.
• Background Zhang ZJ, Bi Y, Li S, Zhang Q, Zhao G, Guo Y, Song Q. Reduced risk of lung cancer with metformin therapy in diabetic patients: a systematic review and meta-analysis. Am J Epidemiol. 2014 Jul 1;180(1):11-4. doi: 10.1093/aje/kwu124. Epub 2014 Jun 10.
• Background Bodmer M, Meier C, Krahenbuhl S, Jick SS, Meier CR. Long-term metformin use is associated with decreased risk of breast cancer. Diabetes Care. 2010 Jun;33(6):1304-8. doi: 10.2337/dc09-1791. Epub 2010 Mar 18.
• Background Pusceddu S, Vernieri C, Di Maio M, Marconcini R, Spada F, Massironi S, Ibrahim T, Brizzi MP, Campana D, Faggiano A, Giuffrida D, Rinzivillo M, Cingarlini S, Aroldi F, Antonuzzo L, Berardi R, Catena L, De Divitiis C, Ermacora P, Perfetti V, Fontana A, Razzore P, Carnaghi C, Davi MV, Cauchi C, Duro M, Ricci S, Fazio N, Cavalcoli F, Bongiovanni A, La Salvia A, Brighi N, Colao A, Puliafito I, Panzuto F, Ortolani S, Zaniboni A, Di Costanzo F, Torniai M, Bajetta E, Tafuto S, Garattini SK, Femia D, Prinzi N, Concas L, Lo Russo G, Milione M, Giacomelli L, Buzzoni R, Delle Fave G, Mazzaferro V, de Braud F. Metformin Use Is Associated With Longer Progression-Free Survival of Patients With Diabetes and Pancreatic Neuroendocrine Tumors Receiving Everolimus and/or Somatostatin Analogues. Gastroenterology. 2018 Aug;155(2):479-489.e7. doi: 10.1053/j.gastro.2018.04.010. Epub 2018 Apr 13.
• Background Seelig E, Meyer S, Timper K, Nigro N, Bally M, Pernicova I, Schuetz P, Muller B, Korbonits M, Christ-Crain M. Metformin prevents metabolic side effects during systemic glucocorticoid treatment. Eur J Endocrinol. 2017 Mar;176(3):349-358. doi: 10.1530/EJE-16-0653. Epub 2017 Jan 10.
• Background Bostrom B, Uppal P, Chu J, Messinger Y, Gandrud L, McEvoy R. Safety and efficacy of metformin for therapy-induced hyperglycemia in children with acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2013 Oct;35(7):504-8. doi: 10.1097/MPH.0b013e31829cdeba.
• Green BJ, Marazzini M, Hershey B, Fardin A, Li Q, Wang Z, Giangreco G, Pisati F, Marchesi S, Disanza A, Frittoli E, Martini E, Magni S, Beznoussenko GV, Vernieri C, Lobefaro R, Parazzoli D, Maiuri P, Havas K, Labib M, Sigismund S, Fiore PPD, Gunby RH, Kelley SO, Scita G. PillarX: A Microfluidic Device to Profile Circulating Tumor Cell Clusters Based on Geometry, Deformability, and Epithelial State. Small. 2022 Apr;18(17):e2106097. doi: 10.1002/smll.202106097. Epub 2022 Mar 28.

Drugs

Indications