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Gastrointestinal tumours, non-colorectal

5988 - New promising combination therapy of a mitochondrial metabolism inhibitor with mFOLFIRINOX in pancreatic cancer


11 Sep 2017


Gastrointestinal tumours, non-colorectal


Angela Alistar


Annals of Oncology (2017) 28 (suppl_5): v209-v268. 10.1093/annonc/mdx369


A.T. Alistar1, B. Pasche2, R. D'Agostino3, T. Pardee4, S. Luther5, R. Desnoyer6

Author affiliations

  • 1 Hematology Oncology, Atlantic Health System, 07962 - morristown/US
  • 2 Hematology Oncology, Wake forest university, winston salem/US
  • 3 Director Of Biostatistic Core, wake forest university, winston salem/US
  • 4 Cmo, Rafael Pharmaceuticals, Cranbury/US
  • 5 Clinical Operations, Rafael pharmaceuticals, Cranbury/US
  • 6 Hematology Oncology, Wake forest university, Winston Salem/US


Abstract 5988


Stage IV pancreatic cancer is a lethal disease. Current standard practice is combination chemotherapy such as FOLFIRINOX or Gemcitabine and Abraxane. The glycolic and mitochondrial metabolism are aberrant in pancreatic cancer and translate into chemoresistance. Inhibition of glutamine metabolism can potentially synergize with therapies that increase intracellular reactive oxygen species such as FOLFIRINOX components. CPI- 613 is a novel antimitocondrial developed by Rafael Pharmaceuticals that showed preclinical activity in pancreatic cancer.


We designed a phase 1 study to evaluate for synergy between CPI -613 and FOLFIRINOX for patients with stage IV pancreatic cancer. Aims: To determine the maximum tolerated dose (MTD) of CPI- 613 when used in combination with modified FOLFIRINOX. To assess the safety of CPI-613 + modified FOLFIRINOX To obtain preliminary data on efficacy of treatment.


Updated Results as of July, 2017 Toxicity: No deaths due to adverse events were reported. The MTD was identified at 500 mg/m2 and a total of 18 patients were treated at the MTD. The most common grade 3–4 non-hematological adverse events: hyperglycemia, hypokalemia, peripheral sensory neuropathy, diarrhea, and abdominal pain. The most common grade 3–4 hematological adverse events: neutropenia, lymphopenia, anemia and thrombocytopenia Preliminary efficacy: Of the 18 patients treated at MTD– 8 patients are alive and 3 patients are still on treatment. The median PFS is 10.4 months, 95% CI (119 to 560 days) – 3 patients are still alive and on treatment who have not progressed. Median overall survival is 20.1 months, data still maturing. The 95% CI cannot be accurately estimated yet. Three patients achieved a complete response.


CPI-613 is a first in class non-redox active lipoate derivative being tested in phase I clinical trial in combination with FOLFIRINOX. The MTD for CPI-613 was identified at 500mg/m2. The treatment combination is feasible and well-tolerated. The response rate was 61%, which is higher than FOLFIRINOX alone (31.6%). The median PFS is 10.4months and the median OS is 20.1 months, data still maturing. A randomized, international phase 3 study of FOLFIRINOX vs. m FOLFIRINOX+ CPI613 will open in 2018.

Clinical trial identification

NCT01835041, First received: April 16, 2013 Last updated: May 30, 2017 Last verified: May 2017

Legal entity responsible for the study

Wake Forest University, School of Medicine


Cornerstone Pharmaceutical now Rafael Pharmaceuticals


T. Pardee: Chief Medical Officer and employee of Rafael Pharmaceutical (name change on June 5th 2017 from Cornerstone Pharmaceutical). Dr Pardee has no stock or equity in the company. S. Luther: Employee of Rafael Pharmaceuticals and the COO of the company. He owns stock in the company. All other authors have declared no conflicts of interest.

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