Safety and Effectiveness Study of Pre-operative Artesunate in Stage II/ III Colorectal Cancer

Summary

TThis study evaluates the safety and effectiveness of pre-operative artesunate, given orally once a day for 14 days prior to surgery, in patients with Stage II/III colorectal cancer. Artesunate is an established antimalarial drug with an excellent safety profile. It is well tolerated, affordable, and widely available. Several laboratory studies and one small pilot clinical study in patients with colorectal cancer have shown that artesunate can reduce the proliferation and growth of cancer cells. One hundred patients diagnosed with Stage II/III operable colorectal cancer will be randomly allocated to receive oral artesunate 200 mg daily or a matching placebo for 14 days prior to surgery. Patients will then be followed closely for 5 years to determine whether pre-operative artesunate reduces the risk of cancer recurrence after surgery.

Timeline

Start

2025-08-15

Primary completion

2032-08-30

Completion

2033-07-31

Publications

• Background Krishna S, Ganapathi S, Ster IC, Saeed ME, Cowan M, Finlayson C, Kovacsevics H, Jansen H, Kremsner PG, Efferth T, Kumar D. A Randomised, Double Blind, Placebo-Controlled Pilot Study of Oral Artesunate Therapy for Colorectal Cancer. EBioMedicine. 2014 Nov 15;2(1):82-90. doi: 10.1016/j.ebiom.2014.11.010. eCollection 2015 Jan.
• Background Kremsner PG, Krishna S. Antimalarial combinations. Lancet. 2004 Jul 17-23;364(9430):285-94. doi: 10.1016/S0140-6736(04)16680-4.
• Background Krishna S, Bustamante L, Haynes RK, Staines HM. Artemisinins: their growing importance in medicine. Trends Pharmacol Sci. 2008 Oct;29(10):520-7. doi: 10.1016/j.tips.2008.07.004. Epub 2008 Aug 25.
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• Background Singh NP, Panwar VK. Case report of a pituitary macroadenoma treated with artemether. Integr Cancer Ther. 2006 Dec;5(4):391-4. doi: 10.1177/1534735406295311.
• Background Steinbruck L, Pereira G, Efferth T. Effects of artesunate on cytokinesis and G(2)/M cell cycle progression of tumour cells and budding yeast. Cancer Genomics Proteomics. 2010 Nov-Dec;7(6):337-46.
• Background Reichert S, Reinboldt V, Hehlgans S, Efferth T, Rodel C, Rodel F. A radiosensitizing effect of artesunate in glioblastoma cells is associated with a diminished expression of the inhibitor of apoptosis protein survivin. Radiother Oncol. 2012 Jun;103(3):394-401. doi: 10.1016/j.radonc.2012.03.018. Epub 2012 May 3.
• Background Nakase I, Lai H, Singh NP, Sasaki T. Anticancer properties of artemisinin derivatives and their targeted delivery by transferrin conjugation. Int J Pharm. 2008 Apr 16;354(1-2):28-33. doi: 10.1016/j.ijpharm.2007.09.003. Epub 2007 Sep 6.
• Background Kim SJ., Kim MS., Lee JW., Lee CH., Yoo, H., Shin, SH., et al. Dihydroartemisinin enhances radiosensitivity of human glioma cells in vitro. J Cancer Res Clin Oncol. 2006;132 :129-135. Krishna K., Ganapathi S., Ster IS., Saeed MEM., Cowan M., Finlayson C., Kovacsevics H., Jansen H., Kremsner PG., Efferth T., Kumar D. A Randomised, Double Blind,Placebo Controlled Pilot Study of Oral Artesunate Therapy for Colorectal Cancer. EBioMedicine 2015;2(1) :82-90 Kreeftmeijer-Vegter, A. R., P. J. van Genderen., Visser LG., Bierman WF., Clerinx J., van Veldhuizen CK., de Vries PJ. "Treatment outcome of intravenous artesunate in patients with severe malaria in the Netherlands and Belgium." Malar J.2012;11:102. Lai H., Nakase I., Lacoste E., Singh NP., Sasaki. Artemisinin-transferrin conjugate retards growth of breast tumors in the rat. Anticancer Res 2009;29 :3807-3810.
• Background Ho WE, Peh HY, Chan TK, Wong WS. Artemisinins: pharmacological actions beyond anti-malarial. Pharmacol Ther. 2014 Apr;142(1):126-39. doi: 10.1016/j.pharmthera.2013.12.001. Epub 2013 Dec 6.
• Background Foxtrot Collaborative Group. Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: the pilot phase of a randomised controlled trial. Lancet Oncol. 2012 Nov;13(11):1152-60. doi: 10.1016/S1470-2045(12)70348-0. Epub 2012 Sep 25.
• Background Finlay IG, Meek D, Brunton F, McArdle CS. Growth rate of hepatic metastases in colorectal carcinoma. Br J Surg. 1988 Jul;75(7):641-4. doi: 10.1002/bjs.1800750707.
• Background Ericsson T, Blank A, von Hagens C, Ashton M, Abelo A. Population pharmacokinetics of artesunate and dihydroartemisinin during long-term oral administration of artesunate to patients with metastatic breast cancer. Eur J Clin Pharmacol. 2014 Dec;70(12):1453-63. doi: 10.1007/s00228-014-1754-2. Epub 2014 Sep 25.
• Background Efferth T, Dunstan H, Sauerbrey A, Miyachi H, Chitambar CR. The anti-malarial artesunate is also active against cancer. Int J Oncol. 2001 Apr;18(4):767-73. doi: 10.3892/ijo.18.4.767.
• Background Du JH, Zhang HD, Ma ZJ, Ji KM. Artesunate induces oncosis-like cell death in vitro and has antitumor activity against pancreatic cancer xenografts in vivo. Cancer Chemother Pharmacol. 2010 Apr;65(5):895-902. doi: 10.1007/s00280-009-1095-5. Epub 2009 Aug 19.
• Background Berger TG, Dieckmann D, Efferth T, Schultz ES, Funk JO, Baur A, Schuler G. Artesunate in the treatment of metastatic uveal melanoma--first experiences. Oncol Rep. 2005 Dec;14(6):1599-603.
• Background Berdelle N, Nikolova T, Quiros S, Efferth T, Kaina B. Artesunate induces oxidative DNA damage, sustained DNA double-strand breaks, and the ATM/ATR damage response in cancer cells. Mol Cancer Ther. 2011 Dec;10(12):2224-33. doi: 10.1158/1535-7163.MCT-11-0534. Epub 2011 Oct 13.
• Background Beccafico S, Morozzi G, Marchetti MC, Riccardi C, Sidoni A, Donato R, Sorci G. Artesunate induces ROS- and p38 MAPK-mediated apoptosis and counteracts tumor growth in vivo in embryonal rhabdomyosarcoma cells. Carcinogenesis. 2015 Sep;36(9):1071-83. doi: 10.1093/carcin/bgv098. Epub 2015 Jul 7.
• Background Anfosso L, Efferth T, Albini A, Pfeffer U. Microarray expression profiles of angiogenesis-related genes predict tumor cell response to artemisinins. Pharmacogenomics J. 2006 Jul-Aug;6(4):269-78. doi: 10.1038/sj.tpj.6500371. Epub 2006 Jan 24.

Drugs

Indications