Normal VolunteersNCT00465842
Protein Biomarker in Hepatocellular Carcinoma
An observational study of Normal Volunteers and Hepatitis, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in Singapore.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Normal Volunteers, Hepatitis, Liver Cirrhosis
- How many people
- 211 participants
- Where
- 1 siteSingapore
- Study dates
- 20 Jun 2006to 14 Aug 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: HCC patients, normal volunteers and patients with hepatitis with/without cirrhosis
Who may be able to join
- Group A: Normal volunteers without any history of liver disease and with normal liver functions test (LFT), including total protein/Albumin, LDH, ALT, AST, GGT, total bilirubin, direct and indirect bilirubin and do not belong to group B. Volunteers will be screened using questionnaires. Those deemed suitable will then be asked to have the blood test done. All blood tests are done free of charge to subjects.
- Group B: Hepatitis B or C carriers with normal liver functions.
- Group C: Hepatitis B or C carriers with abnormal liver functions.
- Group D: Liver cirrhosis, proven by liver biopsy or on clinical evidences, such as varices on CT scan indicative of portal hypertension.
- Group E: HCC patients with resection.
- Group F: Unresectable HCC patients with treatment.
Show all 10Show fewer
- Group G: HCC patients with active malignant disease and only palliative care are offered.
- Signed Informed Consent
- -≥ 18 years of age
- In this trial, diagnosis of HCC is established with either (a) known hepatitis B or C carrier, and space occupying lesion(s) in the liver and AFP > 400ng/ml or (b) cytological or histological confirmation by biopsy
Who cannot join
- There is no exclusion criteria
Trial locations and contacts
1 site in 1 country.
Singapore1 site
Johns Hopkins Singapore International Medical Center
Singapore, 308433
About this study
Official title: Protein Biomarkers for Early Detection and Prognostication in Hepatocellular Carcinoma (HCC)
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.
Read the 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 < 0.001, 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.
- Keywords
- Hepatitis, Liver Cirrhosis, HCC
- Medical subject headings
- Hepatitis, Liver Cirrhosis, Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| A - Normal Volunteers | Normal volunteers without any history of liver disease and with normal liver functions test (LFT), including total protein/Albumin, LDH, ALT, AST, GGT, total bilirubin, direct and indirect bilirubin and do not belong to group B. Volunteers will be screened using questionnaires. Those deemed suitable will then be asked to have the blood test done. All blood tests are done free of charge to subjects. | |
| B - Hepatitis B or C carriers with normal liver functions | Not described | |
| C - Hepatitis B or C carriers with abnormal liver functions | Not described | |
| D - Liver Cirrhosis | Liver cirrhosis, proven by liver biopsy or on clinical evidences, such as varices on CT scan indicative of portal hypertension. | |
| E - Hepatocellular Carcinoma (HCC) with Resection | HCC patients with resection. | |
| F - Unresectable HCC | Unresectable HCC patients with treatment | |
| G - Malignant HCC | HCC patients with active malignant disease and only palliative care are offered. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with presence of serum protein markers
Number of participants with truncated complement C3a, albumin, B2-microglobulin and histidine-rich glycoprotein, IGF-I, and IGF-II on first blood sample.
Measured: Day 1
Secondary outcomes (2)
Number of participants with hepatocellular carcinoma (HCC) with presence of protein markers.
To study the prospective and longitudinal value of these protein markers in detecting HCC by regular measurement of these proteins and follow up with routine clinical practice in high-risk patients.
Measured: up to 5 years
Number of participants with presence of serum protein markers with resectable and unrsectable HCC.
Measured: up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2007 (estimated)
- Study start20 Jun 2006
- Primary completion14 Aug 2013
- Study completion14 Aug 2013
Why it stopped: Loss of funding due to difficulty with recruitment and participant retention.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Normal VolunteersStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 211 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Singapore Cancer Society
- Responsible party
- Sponsor
- Investigators
- Alex Chang, MD, Principal investigator, Johns Hopkins Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00465842
- Sponsor's protocol ID
- JS0541
- Other IDs
- NA_00037477
- Status last verified
- Feb 2019
- First submitted
- 23 Apr 2007
- Last updated
- 15 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Protein Biomarkers for Early Detection and Prognostication in Hepatocellular Carcinoma (HCC)
- ClinicalTrials.gov ID
- NCT00465842
- Acronym / sponsor ID
- JS0541
- Keywords
- Hepatitis, Liver Cirrhosis, HCC
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Loss of funding due to difficulty with recruitment and participant retention.
- Enrolment
- 211 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- Singapore Cancer Society
- Study start
- 20 Jun 2006 (actual)
- Primary completion
- 14 Aug 2013 (actual)
- Study completion
- 14 Aug 2013 (actual)
- First posted
- 25 Apr 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 < 0.001, 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 design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| A - Normal Volunteers | – | –Normal volunteers without any history of liver disease and with normal liver functions test (LFT), including total protein/Albumin, LDH, ALT, AST, GGT, total bilirubin, direct and indirect bilirubin and do not belong to group B. Volunteers will be screened using questionnaires. Those deemed suitable will then be asked to have the blood test done. All blood tests are done free of charge to subjects. |
| B - Hepatitis B or C carriers with normal liver functions | – | – |
| C - Hepatitis B or C carriers with abnormal liver functions | – | – |
| D - Liver Cirrhosis | – | –Liver cirrhosis, proven by liver biopsy or on clinical evidences, such as varices on CT scan indicative of portal hypertension. |
| E - Hepatocellular Carcinoma (HCC) with Resection | – | –HCC patients with resection. |
| F - Unresectable HCC | – | –Unresectable HCC patients with treatment |
| G - Malignant HCC | – | –HCC patients with active malignant disease and only palliative care are offered. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- HCC patients, normal volunteers and patients with hepatitis with/without cirrhosis
Key inclusion criteria (10 listed)
- Group A: Normal volunteers without any history of liver disease and with normal liver functions test (LFT), including total protein/Albumin, LDH, ALT, AST, GGT, total bilirubin, direct and indirect bilirubin and do not belong to group B. Volunteers will be screened using questionnaires. Those deemed suitable will then be asked to have the blood test done. All blood tests are done free of charge to subjects.
- Group B: Hepatitis B or C carriers with normal liver functions.
- Group C: Hepatitis B or C carriers with abnormal liver functions.
- Group D: Liver cirrhosis, proven by liver biopsy or on clinical evidences, such as varices on CT scan indicative of portal hypertension.
- Group E: HCC patients with resection.
Key exclusion criteria (1 listed)
- There is no exclusion criteria
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Number of participants with presence of serum protein markers
Time frame: Day 1
Number of participants with truncated complement C3a, albumin, B2-microglobulin and histidine-rich glycoprotein, IGF-I, and IGF-II on first blood sample.
2 secondary outcomes
Number of participants with hepatocellular carcinoma (HCC) with presence of protein markers.
Time frame: up to 5 years
Number of participants with presence of serum protein markers with resectable and unrsectable HCC.
Time frame: up to 5 years
Results and safety
The study was stopped early (reason given: Loss of funding due to difficulty with recruitment and participant retention.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alex Chang, MD principal investigator
Johns Hopkins Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Normal Volunteers and Hepatitis, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Loss of funding due to difficulty with recruitment and participant retention.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with presence of serum protein markers (time frame: Day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2019.