Effects of OXY111A in Primary and Secondary Hepato-Pancreato-Biliary Neoplasm

Summary

The purpose of the study is to evaluate whether the novel anti-cancer drug OXY111A is safe and tolerated in patients with primary and secondary hepato-pancreato-biliary and gastrointestinal neoplasia as measured by exploring the maximum tolerated dose (MTD). At level of MTD, additional patients will be included aimed for assessing the efficacy profile in these neoplasia entities.

Timeline

Start

2014-02

Primary completion

2016-12

Completion

2016-12

Publications

• Background Aprahamian M, Bour G, Akladios CY, Fylaktakidou K, Greferath R, Soler L, Marescaux J, Egly JM, Lehn JM, Nicolau C. Myo-InositolTrisPyroPhosphate treatment leads to HIF-1alpha suppression and eradication of early hepatoma tumors in rats. Chembiochem. 2011 Mar 21;12(5):777-83. doi: 10.1002/cbic.201000619. Epub 2011 Mar 2.
• Background Derbal-Wolfrom L, Pencreach E, Saandi T, Aprahamian M, Martin E, Greferath R, Tufa E, Choquet P, Lehn JM, Nicolau C, Duluc I, Freund JN. Increasing the oxygen load by treatment with myo-inositol trispyrophosphate reduces growth of colon cancer and modulates the intestine homeobox gene Cdx2. Oncogene. 2013 Sep 5;32(36):4313-8. doi: 10.1038/onc.2012.445. Epub 2012 Oct 8.
• Background Kieda C, El Hafny-Rahbi B, Collet G, Lamerant-Fayel N, Grillon C, Guichard A, Dulak J, Jozkowicz A, Kotlinowski J, Fylaktakidou KC, Vidal A, Auzeloux P, Miot-Noirault E, Beloeil JC, Lehn JM, Nicolau C. Stable tumor vessel normalization with pO(2) increase and endothelial PTEN activation by inositol trispyrophosphate brings novel tumor treatment. J Mol Med (Berl). 2013 Jul;91(7):883-99. doi: 10.1007/s00109-013-0992-6. Epub 2013 Mar 9.
• Background Raykov Z, Grekova SP, Bour G, Lehn JM, Giese NA, Nicolau C, Aprahamian M. Myo-inositol trispyrophosphate-mediated hypoxia reversion controls pancreatic cancer in rodents and enhances gemcitabine efficacy. Int J Cancer. 2014 Jun 1;134(11):2572-82. doi: 10.1002/ijc.28597. Epub 2013 Nov 25.
• Background Fylaktakidou KC, Lehn JM, Greferath R, Nicolau C. Inositol tripyrophosphate: a new membrane permeant allosteric effector of haemoglobin. Bioorg Med Chem Lett. 2005 Mar 15;15(6):1605-8. doi: 10.1016/j.bmcl.2005.01.064.
• Schneider MA, Linecker M, Fritsch R, Muehlematter UJ, Stocker D, Pestalozzi B, Samaras P, Jetter A, Kron P, Petrowsky H, Nicolau C, Lehn JM, Humar B, Graf R, Clavien PA, Limani P. Phase Ib dose-escalation study of the hypoxia-modifier Myo-inositol trispyrophosphate in patients with hepatopancreatobiliary tumors. Nat Commun. 2021 Jun 21;12(1):3807. doi: 10.1038/s41467-021-24069-w.
• Limani P, Linecker M, Kron P, Samaras P, Pestalozzi B, Stupp R, Jetter A, Dutkowski P, Mullhaupt B, Schlegel A, Nicolau C, Lehn JM, Petrowsky H, Humar B, Graf R, Clavien PA. Development of OXY111A, a novel hypoxia-modifier as a potential antitumor agent in patients with hepato-pancreato-biliary neoplasms - Protocol of a first Ib/IIa clinical trial. BMC Cancer. 2016 Oct 19;16(1):812. doi: 10.1186/s12885-016-2855-3.

Drugs

Indications