Clinical trial NCT02036216: Circulating Cell-free DNA as a Predictive Biomarker for Hepatocelluar Carcinoma.
Official title: Detected the Valuable Characteristic Changes Both in Circulating Cell-free DNA and Primary Tumor in the Patients With Hepatocelluar Carcinoma.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hepatocellular Carcinoma
Keywords: Hepatocellular Carcinoma；cell free tumor DNA; Mutation;
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: Stanford University
First posted: 2014-01-14
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The HCC patients who will receive the surgical treatment in Peking Union Medical College Hospital from Jan of 2014 till the end of this study.

Brief summary: Circulating free cell DNA (cfDNA) is extracellular fragmentation of nucleic acids that occurs both in plasma and serum. This kind of DNA which derived from the apoptotic/necrotic cells or the lysis of circulating tumor cells (CTCs) can be detectedin the patients with a variety of diseases. Emerging evidence suggests that cfDNA from patients exhibits characteristicchanges of tumors, suchas mutations, insertions/deletions, methylations,microsatellite aberrations, and copy number variations, etc. All of these reveal a visible difference between the benign conditions, and thus may be useful in the diagnosis of cancer, identification of targeted therapy, monitor responses to treatments, and early detection of relapse. The purpose for this study is to explore these characteristic changes in the patients withhepatocellular carcinoma (HCC) and expect to guide targeted therapy and identify non-invasive biomarkers of cancer diagnosis and prognosis which can be easily isolated from the circulation.

Detailed description: In cancer, cfDNA can be detected a higher concentration in the circulation because of the necrosis of neoplasm cells with the rapid enlargement and relatively shortage of blood supply. So, identifying tumor-specific genetic and epigenetic changes in cfDNA on this status, such as gene mutations, deletions, methylation alterations and microsatellite alterations, may be more specific for us to diagnose the neoplasms in early phase. This phenomenon also appears in the patients with hepatocellular carcinoma (HCC). Studies have shown that cfDNA level is associated with intrahepatic and extrahepatic metastasis in HCC patients and examined some cfDNAcharacteristic changes, such as p161NK4A, RTL, RASSF1A, LINE-1 and GSTP1. Thus is useful for us to explore the specific cfDNA in HCC. For a high sensitivity and specificity detection, we will use technologiesdeveloped at Stanford Genome Technology Centerto find more characteristic gene mutations, methylation alterations or other changes (3). In this study, we willinvestigate thesecharacteristic changesin cfDNA and primary tumor lesions.

Study arrangement:

Collect the DNA samples from the plasma, blood cells and solid tumor tissues in the patients with HCC.

Detect the DNA sequence from the samples of plasma, blood cells and solid tumor tissues.

Identify cancer specific variations in cfDNA and primary tumor lesions. Date analysis and investigate these characteristic changes. Evaluate the application in early diagnosis, treatment monitoring and prognosis for HCC.

Eligibility criteria: Inclusion Criteria:

Age≥18years and ≤80 years; Histologically and cytologically proven Hepatocellular carcinoma Child-Pugh：child A-B Adequate hematological, renal, cardiac and pulmonary functions Tumor in any segment of liver

Exclusion Criteria:

Uncontrolled systemic disease Reject the surgical treatment Metastatic carcinoma Child-Pugh：child C

Primary outcomes:
measure: To collect the DNA samples from the plasma, blood cells and solid tumor tissues in the patients with HCC.
timeFrame: three months
Secondary outcomes:
measure: Investigate the value characteristic changes from the DNA samples.
timeFrame: three months
measure: Date analysis
timeFrame: two months
measure: Evaluate the sensitivity and specificity with these changes in HCC
timeFrame: four months
measure: Early diagnosis, treatment monitoring and prognosis evaluation.
timeFrame: twelve months
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Genome Technology Center
state: California
city: Beijing
country: China
facility: Department of liver surgery; Peking Union Medical College Hospital；
state: Beijing
Study officials:
affiliation: PUMCH
name: Yilei Mao, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chen K, Zhang H, Zhang LN, Ju SQ, Qi J, Huang DF, Li F, Wei Q, Zhang J. Value of circulating cell-free DNA in diagnosis of hepatocelluar carcinoma. World J Gastroenterol. 2013 May 28;19(20):3143-9. doi: 10.3748/wjg.v19.i20.3143.
citation: Gall TM, Frampton AE, Krell J, Habib NA, Castellano L, Stebbing J, Jiao LR. Cell-free DNA for the detection of pancreatic, liver and upper gastrointestinal cancers: has progress been made? Future Oncol. 2013 Dec;9(12):1861-9. doi: 10.2217/fon.13.152.
citation: Shen P, Wang W, Chi AK, Fan Y, Davis RW, Scharfe C. Multiplex target capture with double-stranded DNA probes. Genome Med. 2013 May 29;5(5):50. doi: 10.1186/gm454. eCollection 2013.