Phase I:Decitabine by Hepatic Arterial Infusion(HAI) in Unresectable Liver Metastases Colorectal Cancer (CRC)
Status:
Completed
Trial end date:
2017-07-01
Target enrollment:
Participant gender:
Summary
Despite the advances in the medical treatment of unresectable liver metastases from
colorectal cancer there is currently no curative treatment option available for these
patients. Decitabine is a cytidine analog with proven anti-neoplastic activity in patients
with acute myeloid leukemia and myelodysplastic syndromes. Decitabine causes demethylation of
the DNA strands of replicating cells. Hereby decitabine treatment demethylates the promoter
regions of tumor suppressor- and cancer testis antigen encoding genes leading to expression
of these genes by the cancer cells. The hepatic arterial route for administration of
cytotoxic drugs has been widely explored in treatment of colorectal cancer liver metastases
because these metastases depend for their blood flow from this artery (as opposed to the
normal liver tissue that is mainly dependent from the portal vein). By investigating the
administration of decitabine by hepatic arterial infusion the investigators intend to explore
the potential advantage of minimizing the systemic exposure (and toxicity) and maximizing the
concentration of decitabine within the liver metastasis. The primary objective of this phase
I will be to establish the recommended dose for decitabine by HAI for further use in phase II
trials. The most important secondary objective will be to document the effect of decitabine
by HAI on the expression of cancer testis antigens by the colorectal cancer cells, serving as
a reference for potential further exploration of decitabine by HAI in combination with cancer
immunotherapy