Mechanism of Sorafenib Resistance in Patients With Advanced Hepatocellular Carcinoma
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|ClinicalTrials.gov Identifier: NCT02733809|
Recruitment Status : Recruiting
First Posted : April 12, 2016
Last Update Posted : August 20, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Hepatocellular Carcinoma||Drug: Sorafenib||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Mechanism of Sorafenib Resistance in Patients With Advanced Hepatocellular Carcinoma|
|Study Start Date :||January 2014|
|Estimated Primary Completion Date :||December 2024|
|Estimated Study Completion Date :||December 2024|
Group under the treatment ( sorafenib ) Maximum dose of 400 mg BID If subjects devolves adverse events, dose can be reduced.
Liver lesion biopsy (HCC) and blood samples will be taken from the subjects before starting the treatment course, and another biopsy and blood samples when they devolve a resistance.
Other Name: Nexavar
- Overall and disease-free survival genes. [ Time Frame: 10 years ]Survival analysis
- The predictors of survival ( response to Sorafenib ) [ Time Frame: 10 years ]Survival analysis
- Potential genetic targets for resistance. [ Time Frame: 10 years ]Samples will be sequenced using second generation sequencing comparison between, before and after therapy signature will be identified.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02733809
|Contact: Weam S Hussein, MBBS FRCSC PhD||+966 firstname.lastname@example.org|
|Contact: Mazen M Hassanain||+966 50 514 email@example.com|
|King Saud University Medical City||Recruiting|
|Riyadh, Saudi Arabia, 7805|
|Contact: Weam S Husseim +966541480459 firstname.lastname@example.org|
|Principal Investigator: Dr. Mazen M Hassanain, MBBS FRCSC FACS PhD|
|Sub-Investigator: Prof. Ayman A Abdo, MD, FRCPC, FACP|
|Sub-Investigator: Dr. Khalid A Alswat, MD, ABIM, MRCP,FACP|
|Sub-Investigator: Prof. Waleed K Alhamoudi|
|Principal Investigator: Dr. Shouki M Bazarbashi|
|Principal Investigator:||Mazen M Hassanain, MBBS FRCSC PhD||King Saud University Medical City, Riyadh,KSA.|