Evaluation of the Safety and Efficacy of Esperanza Extract (PA001)

Summary

This is a phase Ib/II clinical study that has two phases. In phase Ib, the safety evaluation of the extract of Petiveria alliacea (Esperanza) will be carried out in patients with metastatic gastrointestinal tumors (colon, pancreas, stomach, and biliary tract) and patients with newly diagnosed and relapsed acute leukemia. In phase IIb, the safety will continue to be evaluated, and the efficacy of the Esperanza extract will be explored in combination with chemotherapy in patients with metastatic gastrointestinal tumors (colon, pancreas, stomach, and biliary tract) with newly diagnosed acute leukemias and relapses.

Timeline

Start

2022-12-15

Primary completion

2023-03-15

Completion

2023-06-15

Publications

• Results Di Martino MT, Zazzeroni F, Donadelli M, Chiodoni C, Caraglia M, Scotlandi K, Meschini S, Leonetti C. Reprogramming Tumor-Immune Cell Interface in Solid and Hematological Malignancies to Enhance Response to Therapy. J Exp Clin Cancer Res. 2018 Mar 5;37(1):48. doi: 10.1186/s13046-018-0710-x. No abstract available.
• Results Uruena C, Sandoval TA, Lasso P, Tawil M, Barreto A, Torregrosa L, Fiorentino S. Evaluation of chemotherapy and P2Et extract combination in ex-vivo derived tumor mammospheres from breast cancer patients. Sci Rep. 2020 Nov 12;10(1):19639. doi: 10.1038/s41598-020-76619-9.
• Results Sharma SV, Lee DY, Li B, Quinlan MP, Takahashi F, Maheswaran S, McDermott U, Azizian N, Zou L, Fischbach MA, Wong KK, Brandstetter K, Wittner B, Ramaswamy S, Classon M, Settleman J. A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell. 2010 Apr 2;141(1):69-80. doi: 10.1016/j.cell.2010.02.027.
• Results Bergers G, Fendt SM. The metabolism of cancer cells during metastasis. Nat Rev Cancer. 2021 Mar;21(3):162-180. doi: 10.1038/s41568-020-00320-2. Epub 2021 Jan 18.
• Results Fong MY, Zhou W, Liu L, Alontaga AY, Chandra M, Ashby J, Chow A, O'Connor ST, Li S, Chin AR, Somlo G, Palomares M, Li Z, Tremblay JR, Tsuyada A, Sun G, Reid MA, Wu X, Swiderski P, Ren X, Shi Y, Kong M, Zhong W, Chen Y, Wang SE. Breast-cancer-secreted miR-122 reprograms glucose metabolism in premetastatic niche to promote metastasis. Nat Cell Biol. 2015 Feb;17(2):183-94. doi: 10.1038/ncb3094. Epub 2015 Jan 26.
• Results Eddy RJ, Weidmann MD, Sharma VP, Condeelis JS. Tumor Cell Invadopodia: Invasive Protrusions that Orchestrate Metastasis. Trends Cell Biol. 2017 Aug;27(8):595-607. doi: 10.1016/j.tcb.2017.03.003. Epub 2017 Apr 12.
• Results Kang X, Wang J, Li C. Exposing the Underlying Relationship of Cancer Metastasis to Metabolism and Epithelial-Mesenchymal Transitions. iScience. 2019 Nov 22;21:754-772. doi: 10.1016/j.isci.2019.10.060. Epub 2019 Oct 31.
• Results Xian ZY, Liu JM, Chen QK, Chen HZ, Ye CJ, Xue J, Yang HQ, Li JL, Liu XF, Kuang SJ. Inhibition of LDHA suppresses tumor progression in prostate cancer. Tumour Biol. 2015 Sep;36(10):8093-100. doi: 10.1007/s13277-015-3540-x. Epub 2015 May 16.
• Results Zhu J, Ma J, Wang X, Ma T, Zhang S, Wang W, Zhou X, Shi J. High Expression of PHGDH Predicts Poor Prognosis in Non-Small Cell Lung Cancer. Transl Oncol. 2016 Dec;9(6):592-599. doi: 10.1016/j.tranon.2016.08.003.
• Results Butler LM, Perone Y, Dehairs J, Lupien LE, de Laat V, Talebi A, Loda M, Kinlaw WB, Swinnen JV. Lipids and cancer: Emerging roles in pathogenesis, diagnosis and therapeutic intervention. Adv Drug Deliv Rev. 2020;159:245-293. doi: 10.1016/j.addr.2020.07.013. Epub 2020 Jul 23.
• Results Shah US, Dhir R, Gollin SM, Chandran UR, Lewis D, Acquafondata M, Pflug BR. Fatty acid synthase gene overexpression and copy number gain in prostate adenocarcinoma. Hum Pathol. 2006 Apr;37(4):401-9. doi: 10.1016/j.humpath.2005.11.022. Epub 2006 Feb 7.
• Results Koundouros N, Poulogiannis G. Reprogramming of fatty acid metabolism in cancer. Br J Cancer. 2020 Jan;122(1):4-22. doi: 10.1038/s41416-019-0650-z. Epub 2019 Dec 10.
• Results Itkonen HM, Brown M, Urbanucci A, Tredwell G, Ho Lau C, Barfeld S, Hart C, Guldvik IJ, Takhar M, Heemers HV, Erho N, Bloch K, Davicioni E, Derua R, Waelkens E, Mohler JL, Clarke N, Swinnen JV, Keun HC, Rekvig OP, Mills IG. Lipid degradation promotes prostate cancer cell survival. Oncotarget. 2017 Jun 13;8(24):38264-38275. doi: 10.18632/oncotarget.16123.
• Results Zadra G, Photopoulos C, Tyekucheva S, Heidari P, Weng QP, Fedele G, Liu H, Scaglia N, Priolo C, Sicinska E, Mahmood U, Signoretti S, Birnberg N, Loda M. A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis. EMBO Mol Med. 2014 Apr;6(4):519-38. doi: 10.1002/emmm.201302734. Epub 2014 Feb 4.
• Results Song K, Li M, Xu X, Xuan LI, Huang G, Liu Q. Resistance to chemotherapy is associated with altered glucose metabolism in acute myeloid leukemia. Oncol Lett. 2016 Jul;12(1):334-342. doi: 10.3892/ol.2016.4600. Epub 2016 May 17.
• Results Song K, Li M, Xu XJ, Xuan L, Huang GN, Song XL, Liu QF. HIF-1alpha and GLUT1 gene expression is associated with chemoresistance of acute myeloid leukemia. Asian Pac J Cancer Prev. 2014;15(4):1823-9. doi: 10.7314/apjcp.2014.15.4.1823.
• Results Herst PM, Howman RA, Neeson PJ, Berridge MV, Ritchie DS. The level of glycolytic metabolism in acute myeloid leukemia blasts at diagnosis is prognostic for clinical outcome. J Leukoc Biol. 2011 Jan;89(1):51-5. doi: 10.1189/jlb.0710417. Epub 2010 Oct 19.
• Results Guerra F, Arbini AA, Moro L. Mitochondria and cancer chemoresistance. Biochim Biophys Acta Bioenerg. 2017 Aug;1858(8):686-699. doi: 10.1016/j.bbabio.2017.01.012. Epub 2017 Feb 1.
• Results Bokil A, Sancho P. Mitochondrial determinants of chemoresistance. Cancer Drug Resist. 2019 Sep 19;2(3):634-646. doi: 10.20517/cdr.2019.46. eCollection 2019.
• Results Panina SB, Baran N, Brasil da Costa FH, Konopleva M, Kirienko NV. A mechanism for increased sensitivity of acute myeloid leukemia to mitotoxic drugs. Cell Death Dis. 2019 Aug 13;10(8):617. doi: 10.1038/s41419-019-1851-3.
• Results Sriskanthadevan S, Jeyaraju DV, Chung TE, Prabha S, Xu W, Skrtic M, Jhas B, Hurren R, Gronda M, Wang X, Jitkova Y, Sukhai MA, Lin FH, Maclean N, Laister R, Goard CA, Mullen PJ, Xie S, Penn LZ, Rogers IM, Dick JE, Minden MD, Schimmer AD. AML cells have low spare reserve capacity in their respiratory chain that renders them susceptible to oxidative metabolic stress. Blood. 2015 Mar 26;125(13):2120-30. doi: 10.1182/blood-2014-08-594408. Epub 2015 Jan 28.
• Results Yang J, Ren B, Yang G, Wang H, Chen G, You L, Zhang T, Zhao Y. The enhancement of glycolysis regulates pancreatic cancer metastasis. Cell Mol Life Sci. 2020 Jan;77(2):305-321. doi: 10.1007/s00018-019-03278-z. Epub 2019 Aug 20.
• Results Donadelli M, Dando I, Dalla Pozza E, Palmieri M. Mitochondrial uncoupling protein 2 and pancreatic cancer: a new potential target therapy. World J Gastroenterol. 2015 Mar 21;21(11):3232-8. doi: 10.3748/wjg.v21.i11.3232.
• Results Lu W, Hu Y, Chen G, Chen Z, Zhang H, Wang F, Feng L, Pelicano H, Wang H, Keating MJ, Liu J, McKeehan W, Wang H, Luo Y, Huang P. Novel role of NOX in supporting aerobic glycolysis in cancer cells with mitochondrial dysfunction and as a potential target for cancer therapy. PLoS Biol. 2012;10(5):e1001326. doi: 10.1371/journal.pbio.1001326. Epub 2012 May 8.
• Ballesteros-Ramirez R, Pinilla P, Sanchez J, Arevalo M, Sanchez E, Aschner P, Uruena C, Fiorentino S. Exploring the safety and efficacy of phytomedicine Petiveria alliacea extract (Esperanza) in patients with metastatic gastrointestinal tumors and acute leukemias: study protocol for a phase Ib/randomized double blind phase II trial (PA001). BMC Complement Med Ther. 2023 Aug 10;23(1):284. doi: 10.1186/s12906-023-04109-2.

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Indications