Cholesterol Disruption in Combination With FOLFIRINOX in Patients With Metastatic Pancreatic Adenocarcinoma

Official Title

A Phase 1 Feasibility Study of Cholesterol Metabolism Disruption (Evolocumab, Atorvastatin and Ezetimibe) in Combination With FOLFIRINOX in Patients With Metastatic Pancreatic Adenocarcinoma

Summary:

Cardiovascular diseases and cancers, the two leading causes of death in Canada, require cholesterol to sustain their progression. All cells require cholesterol, but cancer cells have much higher needs to sustain growth, division and metastasis. The availability of new cholesterol-lowering drugs developed to protect patients from heart diseases has resulted in unprecedented low levels of cholesterol. The combination of atorvastatin, ezetimibe and Repatha, which are 3 cholesterol-lowering drugs used in combination, is safe, well tolerated and efficient over years of treatment. Recent reports indicate that abundant cholesterol supplies are required to sustain the progression of pancreatic ductal adenocarcinomas. This proof-of-concept study aims to verify the feasibility, the acceptability and gain preliminary data on adding a cholesterol shortage on top of FOLFIRINOX (standard chemotherapy) in newly diagnosed patients with metastatic pancreatic adenocarcinomas. It is expected that a drug-induced cholesterol shortage will slow-down or stop the progression of pancreatic adenocarcinomas while increasing the response to chemotherapy.

Trial Description

Primary Outcome:

  • Safety as measured by the rate of adverse events
  • Characterization of dose-limiting toxicities
Secondary Outcome:
  • LDLR (low-density lipoprotein receptor) changes in response to the multipathway cholesterol embargo.
  • LRP1 (Low-density lipoprotein Receptor-Related Protein 1) changes in response to the multipathway cholesterol embargo.
  • NPC1L1 (Niemann-Pick C1-Like 1 protein) changes in response to the multipathway cholesterol embargo.
  • SRB1 (Scavenger Receptor class B type 1) changes in response to the multipathway cholesterol embargo.
  • Changes in TILs (Tumour Infiltrating Lymphocytes) in response to the multipathway cholesterol embargo.
  • PD-L1 (Programmed Death-Ligand-1) changes in response to the multipathway cholesterol embargo.
  • Tumoural lipid droplet content changes in response to the multipathway cholesterol embargo.

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society