Ignite Creation Date:
2024-05-05 @ 5:29 PM
Last Modification Date:
2024-10-26 @ 9:32 AM
Study NCT ID:
NCT00465842
Status:
TERMINATED
Last Update Posted:
2019-02-15
First Post:
2007-04-23
Brief Title:
Protein Biomarker in Hepatocellular Carcinoma
Sponsor:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Organization:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Overview
Official Title:
Protein Biomarkers for Early Detection and Prognostication in Hepatocellular Carcinoma HCC
Status:
TERMINATED
Status Verified Date:
2019-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Loss of funding due to difficulty with recruitment and participant retention
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Hepatocellular carcinoma HCC is the fifth commonest cancer in the world with poor prognosis as the annual mortality is almost equivalent to the incidence This is mainly due to late diagnosis and co-morbid liver dysfunction HCC is prevalent in our region than in the West due to prevalent Hepatitis B infection and carriers At the time of diagnosis only 10 - 20 of HCC patients are candidates for liver resection or transplantation Almost 40-50 of patients have such poor liver function and co-morbid conditions that only supportive cares are offered Thus the median survival time is 18-24 months for resectable disease 6 months for unresectabe disease and 3 months for metastatic disease
Current screening methods for HCC in high risk patients depend on alpha-fetoprotein AFP and ultrasound of the liver Neither test is sensitive or specific enough for early detection Therefore early diagnosis with novel protein biomarkers is needed urgently and may provides hope to improve treatment outcome
Our preliminary study in 49 HCC patients have identified several proteins such as truncated complement C3a albumin B2 microglobulin may be potentially helpful in early diagnosis We have started a large prospective and longitudinal study in July 2006 with nearly 100 patients accrued This application is to extend and expand our current study We aim to i identify and validate novel protein biomarkers for early diagnosis of HCC ii conduct longitudinal proteomics with most up-to-date methods to discover new biomarker for early detection and prognostication of HCC iii set up gene and plasma depository and clinical database for HCC in collaboration with Singapore Tissue Network
Current screening methods for HCC in high risk patients depend on alpha-fetoprotein AFP and ultrasound of the liver Neither test is sensitive or specific enough for early detection Therefore early diagnosis with novel protein biomarkers is needed urgently and may provides hope to improve treatment outcome
Our preliminary study in 49 HCC patients have identified several proteins such as truncated complement C3a albumin B2 microglobulin may be potentially helpful in early diagnosis We have started a large prospective and longitudinal study in July 2006 with nearly 100 patients accrued This application is to extend and expand our current study We aim to i identify and validate novel protein biomarkers for early diagnosis of HCC ii conduct longitudinal proteomics with most up-to-date methods to discover new biomarker for early detection and prognostication of HCC iii set up gene and plasma depository and clinical database for HCC in collaboration with Singapore Tissue Network
Detailed Description:
Up to 40 of HCC patients have normal AFP Moreover AFP can also be elevated in patients with cirrhosis or exacerbation of chronic hepatitis Prospective studies evaluating the value of AFP in HCC surveillance have reported sensitivities of 39-64 specificity of 76-91 and positive predictive values of 9 -32 9-11
Recently a small handful of biomarkers were identified in the blood of 49 HCC patients by SELDI MS proteomic analysis of their blood with specificity and sensitivity both at 90 12 13 These were truncated complement C3a albumin B2 microglobulin and histidine-rich glycoprotein In addition insulin growth factor IGF and its binding protein have been shown to be novel biomarkers of HCC 14-17 A larger prospective study is necessary to validate these findings
Other investigators have also used Surface-enhanced laser desorption ionization time-of-flight mass spectrometry SELDI to study proteomics in HCC Most of the studies included small numbers of patients and did not include independent test set or report on reproducibility most of the time Thus controversies continue on both the technology of SELDI and validation of the findings Nevertheless Ward et al reported that Kappa and Lumda immunoglobulin light chains were elevated by an average pf 50 in the serum of HCC patients p 0001 sensitivity 94 specificity 86 with Hepatitis C related cirrhosis 18 Schwegler et al reported that SELDI-TOF MS profiling of serum can distinguish chronic Hepatitis C from HCV- related HCC with a sensitivity of 61 and a specificity of 76 Sensitivity and specificity can be improved with the addition of AFP des-gamma carboxyprothrombin and GP73 19 Other reports also indicated potential marker of heat-shock protein 27 20 and complement C3a 21 However all studies lack prospective and longitudinal follow-up with multiple serum samples from same patient Our trial is designed to test the changes of proteomic overtime to identify the earliest possible biomarkers for HCC
Recently a small handful of biomarkers were identified in the blood of 49 HCC patients by SELDI MS proteomic analysis of their blood with specificity and sensitivity both at 90 12 13 These were truncated complement C3a albumin B2 microglobulin and histidine-rich glycoprotein In addition insulin growth factor IGF and its binding protein have been shown to be novel biomarkers of HCC 14-17 A larger prospective study is necessary to validate these findings
Other investigators have also used Surface-enhanced laser desorption ionization time-of-flight mass spectrometry SELDI to study proteomics in HCC Most of the studies included small numbers of patients and did not include independent test set or report on reproducibility most of the time Thus controversies continue on both the technology of SELDI and validation of the findings Nevertheless Ward et al reported that Kappa and Lumda immunoglobulin light chains were elevated by an average pf 50 in the serum of HCC patients p 0001 sensitivity 94 specificity 86 with Hepatitis C related cirrhosis 18 Schwegler et al reported that SELDI-TOF MS profiling of serum can distinguish chronic Hepatitis C from HCV- related HCC with a sensitivity of 61 and a specificity of 76 Sensitivity and specificity can be improved with the addition of AFP des-gamma carboxyprothrombin and GP73 19 Other reports also indicated potential marker of heat-shock protein 27 20 and complement C3a 21 However all studies lack prospective and longitudinal follow-up with multiple serum samples from same patient Our trial is designed to test the changes of proteomic overtime to identify the earliest possible biomarkers for HCC
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NA_00037477 | OTHER | JHM IRB | None |