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. 2019 Oct;15(28):3189-3196.
doi: 10.2217/fon-2019-0209. Epub 2019 Sep 12.

A Phase III open-label trial to evaluate efficacy and safety of CPI-613 plus modified FOLFIRINOX (mFFX) versus FOLFIRINOX (FFX) in patients with metastatic adenocarcinoma of the pancreas

Philip A Philip  1 , Marc E Buyse  2 , Angela T Alistar  3 , Caio MSPR Rocha Lima  4 , Sanjeev Luther  5 , Timothy S Pardee  4   5 , Eric Van Cutsem  6
Affiliations

A Phase III open-label trial to evaluate efficacy and safety of CPI-613 plus modified FOLFIRINOX (mFFX) versus FOLFIRINOX (FFX) in patients with metastatic adenocarcinoma of the pancreas

Philip A Philip et al. Future Oncol. 2019 Oct.

Abstract

Devimistat (CPI-613®) is a novel lipoate analog that inhibits the tricarboxcylic acid cycle at two key carbon entry points. Through its inhibition of pyruvate dehydrogenase and a-ketoglutarate dehydrogenase complexes, devimistat inhibits the entry of glucose and glutamine derived carbons, respectively. Pancreatic cancer is dependent on mitochondrial function for enhanced survival and aggressiveness. In a Phase I study of modified FOLFIRINOX, in combination with devimistat for metastatic pancreatic cancer patients, there was a 61% objective response rate including a 17% complete response rate. This report outlines the rationale and design of the AVENGER 500 study, a Phase III clinical trial of devimistat in combination with modified FOLFIRINOX compared with FOLFIRINOX alone for patients with previously untreated metastatic adenocarcinoma of the pancreas. Clinical trial registration: NCT03504423.

Keywords: CPI-613; FOLFIRINOX; Phase III; metastatic; pancreatic cancer.

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Conflict of interest statement

Financial & competing interests disclosures

AT Alistar has been a consultant for Rafael Pharmaceuticals, S Luther and TS Pardee are employees of Rafael Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Figures

Figure 1.
Figure 1.. Avenger 500 trial schema.
DOR: Duration of response; ECG: Electrocardiogram; ECOG: Eastern Cooperative Oncology Group; ORR: Objective response rate; PFS: Progression-free survival; PK: Pharmacokinetics; PROs: Patient-reported outcomes.
See this image and copyright information in PMC

References

    1. Kamisawa T, Wood LD, Itoi T, Takaori K. Pancreatic cancer. Lancet 388(10039), 73–85 (2016). - PubMed
    1. Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. N. Engl. J. Med. 371(11), 1039–1049 (2014). - PubMed

    2. • An excellent review on pancreatic cancer outlining the clinical and biological features of the disease.

    1. Conroy T, Desseigne F, Ychou M. et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N. Engl. J. Med. 364(19), 1817–1825 (2011). - PubMed

    2. • Reports the Phase III results of FOLOFIRINOX in metastatic pancreatic cancer patients.

    1. Von Hoff DD, Ervin T, Arena FP. et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N. Engl. J. Med. 369(18), 1691–1703 (2013). - PMC - PubMed
    1. Vaziri-Gohar A, Zarei M, Brody JR, Winter JM. Metabolic dependencies in pancreatic cancer. Front. Oncol. 8, 617 (2018). - PMC - PubMed

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