Clinical trial NCT03432624: Detection of MicroRNA-25 in the Diagnosis of Pancreatic Cancer
Official title: A Clinical Validation Study on the Efficacy of MicroRNA-25 Level Detection in Assisting the Diagnosis of Pancreatic Cancer
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Carcinoma, Pancreatic Ductal
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2018-02-14
Enrollment: 750
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed and treated at the Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Fourfold Table Analysis Indexes
timeFrame: throughout the trial, average one year
Secondary outcomes:
measure: Statistical Analysis Indexes
timeFrame: throughout the trial, average one year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan University
state: Shanghai
Study officials:
References: