Mechanism of Sorafenib Resistance in Patients With Advanced Hepatocellular Carcinoma
Status:
Recruiting
Trial end date:
2024-12-01
Target enrollment:
Participant gender:
Summary
It has been shown previously that gene expression profiling signature (a set of dysregulated
genes) can be used for molecular classification, diagnosis, and prognosis of several types of
cancers. In This study the hypothesise that resistant tumor may be due to genetic mutations
and/or other alternative pathways that could be the reason to overcome the Sorafenib and
still proliferate.
Primary objectives To evaluate the primary and secondary potential mechanisms by which HCC
patients on Sorafenib treatment would be resistant to therapy and also identify the favorable
genetic makeup of patients responding to treatment.
Measures of primary outcome:
- cDNA microarray analysis on the MAP kinase pathway.
- mRNA quantification of genetic expression (RT-PCR) for identification of upregulated
genes, and confirmed by corresponding proteomic testing (by Mass Spectroscopy) in the
serum for potential serum markers. Secondary Objectives Progression free survival: Time
to disease progression in patients in Saudi Arabia with HCC receiving Sorafenib:
[defined as time, in weeks, from the baseline visit to progression of the disease or
death from any cause] will be diagnosed using the RECIST criteria based on a trimestrial
abdominal CT evaluation.
- Survival rates and Predictors of survival:
- Survival defined as the time from baseline visit to death from any cause [in
weeks].
- Variables identified in multivariate regression analysis from overall treated
patients independently associated with survival till study completion or death.
Justification and Value to the Kingdom Sorafenib in the treatment of advanced HCC
is a recent development. Since the only current effective treatment for advanced
HCC is resection or transplantation and the list for these procedures are
ever-growing due to the confounding effect of the lack of infrastructure in the
Kingdom, selecting treatment for patients who are more likely to respond to
Sorafenib treatment The Long-Term Comprehensive National Plan for Science,
Technology and Innovation will help to reduce costs of managing HCC. Among Saudi
Arabia population, there are a unique set of patients here (e.g. non-alcohol
related HCC, genotype 4 HCV patients and genotype D HBV patients, high percentage
of obese patients i.e. NASH) which is different from other parts of the world.
There is increasing incidence of HCC in Saudi Arabia. Due to available expertise in
management of HCC patients in the participating institutions in the study, this
project will represent a bridge for the transfer of technology so that our research
staff and doctors will have more expertise in carrying out these techniques
independently. This study will also run in parallel to the on-going initiative to
start a HCC biobanking establishment which will provide the samples needed to carry
out our genetic studies in future. Finally, since the use of Sorafenib (at present,
the only approved treatment for advanced HCC) in the treatment of advanced HCC is a
new field, the findings of our study will have important implications in the
management of HCC, both locally and internationally.
HCC is the third most common cancer in Saudi Arabia. In 2001, HCC was the second most common
cancer affecting Saudi males and the eighth most common cancer affecting females. Most of
patients (90%) present at a more advanced stage when symptoms prevail.
Given the high prevalence of HCC in the Kingdom, it is pertinent to study why some patients
are resistant to Sorafenib compared to others. Elucidation of the differences in mechanisms
among responders and non-responders to Sorafenib therapy will enable physicians to make
better decisions in terms of treating Saudi HCC patients.