Detection of MicroRNA-25 in the Diagnosis of Pancreatic Cancer

Carcinoma, Pancreatic Ductal Clinical Trial

Official title:

A Clinical Validation Study on the Efficacy of MicroRNA-25 Level Detection in Assisting the Diagnosis of Pancreatic Cancer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03432624
• Other study ID #: CSPAC-030
• Status: Not yet recruiting
• Phase: N/A
• First received: January 24, 2018
• Last updated: February 12, 2018
• Start date: March 1, 2018
• Est. completion date: January 1, 2019

Study information

• Verified date: February 2018
• Source: Fudan University
• Contact: Xianjun Yu, doctor
• Phone: +86-21-6417-5590
• Email: yuxianjun[@]fudanpci.org
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Pancreatic cancer represents the most lethal of the common malignancies, with a 5-year survival rate of less than 5%. For patients who, when are diagnosed of pancreatic cancer, are eligible for potentially curative resection, the mortality and morbidity rates after surgery can improve significantly, but who accounts for no more than 20% of all pancreatic patients. It is therefore an effective way to improve the treatment efficacy for pancreatic cancer by discovering novel detection methods for pancreatic cancer, especially at early stages. MicroRNAs have been proved in recent years as functional disease markers, and circulating microRNA-25 is reported of high pancreatic cancer specificity and can be used as a novel marker for pancreatic cancer. A detection kit "MicroRNA (microRNA-25) Qualitative Detection Kit (Fluorescent PCR Method)" is produced and proven to be effective in assisting the diagnosis of pancreatic cancer through clinical trials held independently in three state-level hospitals in China. To further validate the efficacy of the kit, the researchers in this study intend to compare the sensibility and specificity of microRNA-25 level detection and other diagnosis methods, including detection of conventional tumor markers (CA19-9, CA125, CA50, CEA) and imaging (CT, MRI, PET/CT), both in separation and combined, in the diagnosis of pancreatic cancer.

Description:

Pancreatic cancer (mainly pancreatic ductal adenocarcinoma, PDAC) is a disease with extremely poor prognosis, and is often fatal. Surgical resection is the only potentially curative technique for management of PDAC, but only approximately 15% to 20% of patients are candidates for pancreatectomy at the time of diagnosis. For these patients, however, the mortality and morbidity rates after surgery can improve significantly. It is therefore an effective way to improve the treatment efficacy for pancreatic cancer by discovering novel detection methods for pancreatic cancer, especially at early stages.

MicroRNAs are a type of non-encoding single-stranded small RNAs with a length of ~22nt. They can regulate the expression of their target mRNAs by inhibiting their translation into proteins. MicroRNAs participate in all physiological and pathological activities, and their abnormal expression profiles are proven to be closely related to the occurrence and development of diseases, including cancer. Recent studies have further proved that not only tissue/cell-line based microRNAs, but circulating microRNAs can be stably detected, and their expression profiles can function as novel markers to be used in the diagnosis and prognosis of diseases.

Pancreatic cancer specific microRNA profiles have also been reported, amongst which microRNA-25 is found to be significantly upregulated in pancreatic cancer patients. There are also studies try to improve the efficacy of pancreatic cancer diagnosis by combining detection of microRNA and CA19-9. Further are there studies proving microRNA-25 as a highly potential marker for pancreatic cancer. A detection kit "MicroRNA (microRNA-25) Qualitative Detection Kit (Fluorescent PCR Method)" is produced and proven to be effective in assisting the diagnosis of pancreatic cancer through clinical trials held independently in three state-level hospitals in China.

To further validate the efficacy of the kit, the researchers in this study intend to compare the sensibility and specificity of microRNA-25 level detection and other diagnosis methods, including detection of conventional tumor markers (CA19-9, CA125, CA50, CEA) and imaging (CT, MRI, PET/CT), both in separation and combined, with Cohort One in the diagnosis of pancreatic cancer at early stages, to validate the efficacy of microRNA-25 detection in the differentiation of pancreatic cancer and other related diseases, to investigate the relation between microRNA-25 level and pancreatic staging. Patients in Group One will receive a microRNA-25 level detection at the time of diagnosis, along with conventional tumor marker detection and imaging tests, and then be confirmed by pathological study. And, to investigate the efficacy of microRNA-25 level detection in the curative efficacy evaluation and relapse monitoring, patients of Group Two (selected from Group One) will receive a microRNA-25 level detection within one month after surgery and before starting adjuvant therapy, followed by a microRNA-25 level detection every three months along with normal follow-up tests, until relapse is observed with imaging tests.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 750
• Est. completion date: January 1, 2019
• Est. primary completion date: October 1, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Group One:

1. Patient aged 18 years old and above at the time of signing the ICF.

2. Prior to blood sample withdraw, patient not treated with systematic anti-tumor therapy, including long-acting somatostatin analogues, interferons, PRRT (Peptide Receptor- Radionuclide Therapy), mTOR inhibitors and chemotherapy; not treated with radiotherapy or neo-adjuvant therapies.

3. Differences:

Experiment Subgroup: Patients diagnosed or highly-suspected of pancreatic cancer, among whom:

Operable: Patients confirmed with pancreatic cancer by pathological test, and evaluated by MDT as "operable" and "probably operable"; Not operable: Patients confirmed with pancreatic cancer by cytological test (exfoliative cytology or fine needle puncture biopsy), or highly suspected of pancreatic cancer by the MDT referring to disease history, clinical manifestations, lab test and imagining results.

Control Subgroup: Patients confirmed with gallbladder carcinoma, biliary tract lower segment carcinoma, and gastrointestinal carcinoma by pathological test.

Interference Subgroup: Patients diagnosed of chronic pancreatitis, IPMN (intraductal papillary mucinous neoplasm), SPT (solid pseudopapillary tumor of pancreas), pancreatic cystic adenoma.

Group Two:

1. Patient aged 18 years old and above at the time of signing the ICF, and with an expected survival time of over 12 months.

2. Prior to the first blood sample withdraw after surgery, patient not treated with radiotherapy or adjuvant therapy.

3. Differences:

Experiment Subgroup: Patients confirmed of pancreatic cancer and received successful curative operation.

Control Subgroup: Patients confirmed of gallbladder carcinoma and biliary tract lower segment carcinoma, and received successful curative operation.

Exclusion Criteria

Group One:

1. Patient in the period of acute infection.

2. Patient treated with therapies or drugs prior to blood withdraw.

3. Blood sample shows jaundice (TBIL=17.1µmol/L) and hematolysis (to be decided by the serum sample preparer).

4. Blood sample has been stored for one year and above.

Group Two:

1. Patient treated with therapies or drugs prior to first blood withdraw after surgery.

2. Patient shows symptoms of remote metases.

3. Blood sample shows jaundice (TBIL=17.1µmol/L) and hematolysis (to be decided by the serum sample preparer).

4. Blood sample has been stored for one year and above.

Related Conditions & MeSH terms

• Carcinoma, Pancreatic Ductal
• Pancreatic Neoplasms

Intervention

Diagnostic Test:
• Serum MicroRNA-25 detection
The level of microRNA-25 in serum of patients will be detected using the MicroRNA (microRNA-25) Qualitative Detection Kit (Fluorescent PCR Method) and following the manufacture's instruction.*all arms are given the same intervention.

Locations

Country	Name	City	State
China	Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fourfold Table Analysis Indexes	Using the Fourfold Table to analyze the diagnosis value of the tested reagent in comparison with the golden standard (pathological test) from mainly four indexes: Sensitivity, Specificity, Total Coincidence Rate and Youden Index (%).; Fourfold Table Tested reagent Golden standard Total Positive (D+) Negative (D-) Positive (T+) a b a+b Negative (T-) c d c+d Total a+c b+d N=a+b+c+d; Sensitivity: Se=P(T+|D+)=a/(a+c); Specificity: Sp=P(T-|D-)=d/(b+d); Total Coincidence Rate: TC= (a+d)/N; Youden Index: YI=Se+Sp-1	throughout the trial, average one year
Secondary	Statistical Analysis Indexes	Statistical Analysis will evaluate the diagnosing efficacy of the tested reagent with two indexes, Kappa Value and AUC: Kappa Value (K Value) Analysis: to investigate the consistency of the tested reagent with golden standard.; The definition of K is: K=(p_0-p_e)/(1-p_e ), Where p0 is the relative observed agreement of the tested reagent and/or the comparison reagents (identical to accuracy), and pe is the hypothetical probability of chance agreement, using the observed data to calculate the probabilities of each observer randomly seeing each category.; AUC (%): to investigate the diagnosing efficacy of the tested reagent through calculating the AUC (Area Under the ROC Curve).; The ROC curve is created by plotting the true positive rate (TPR) against the false positive rate (FPR) at various threshold setting. The TPR is also known as sensitivity. The FPR is also known as the fall-out or probability of false alarm and can be calculated as (1-specificity).	throughout the trial, average one year