Celebrex and Metformin for Postoperative Hepatocellular Carcinoma

Study Overview
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Brief Summary
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This prospective trial aims to compare the role of celebrex alone, metformin alone, and celebrex plus metformin in preventing HCC recurrence after hepatic resection.

Detailed Description
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Hepatic resection is a popular curative treatment for patients with early-stage HCC and well-preserved liver function. Although overall survival after resection has been increasing, the median 5-year disease-free survival rate after resection remains at only about 37% for early-stage HCC. In fact, the 5-year recurrence rate is as high as 74% for intermediate and advanced HCC. Postoperative recurrence may be due to intrahepatic metastasis arising from the primary tumor or it may be de novo metastasis (multicentric) that arises spontaneously in the residual liver. Intrahepatic metastasis is the primary mechanism of early recurrence, which occurs <2 years after resection; multicentric metastasis is the principal mechanism behind late recurrence, which occurs at least 2 years after resection. In the past few years, some observational studies with small sample size found metformin and celebrex (selective cyclic oxidase-2 inhibitors) may reduce the rate of HCC after surgery. However, no prospective study compare their efficacy in preventing HCC recurrence. This trial aims to compare the role of celebrex alone, metformin alone, and celebrex plus metformin in preventing HCC recurrence after hepatic resection.

Official Title
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Celebrex and Metformin for Postoperative Hepatocellular Carcinoma

Conditions
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Liver Cancer

Intervention / Treatment
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* Drug: Celebrex plus Metformin
* Drug: Celebrex
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 years Diagnosis of HCC was confirmed by histopathological examination of surgical samples in all patients Patients have Child-Pugh A or B liver function No previous neoadjuvant treatment No evidence of macrovascular invasion, metastasis to the lymph nodes and/or distant metastases on the basis of preoperative imaging results and perioperative findings No malignancy other than HCC for 5 years prior to the initial HCC treatment Exclusion Criteria: History of cardiac disease Known history of human immunodeficiency virus (HIV) infection Known Central Nervous System tumors including metastatic brain disease History of organ allograft Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study Pregnant or breast-feeding patients

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Celebrex<br>Patients will receive celebrex (1 piece/day, 0.2mg/piece, Pfizer Pharmaceuticals Ltd) until obvious side effects. | Drug: Celebrex<br>* This group patients will receive celebrex.<br>|
| Experimental: Metformin<br>Patients will receive metformin (1 piece/bid, 250 mg/piece) until obvious side effects. | Drug: Metformin<br>* This group patients will receive metformin.<br>|
| Active Comparator: Celebrex plus Metformin<br>Patients will receive celebrex (1 piece/day, 0.2mg/piece, Pfizer Pharmaceuticals Ltd) until obvious side effects. In addition, patients will receive metformin (1 piece/bid, 250 mg/piece) until obvious side effects. | Drug: Celebrex plus Metformin<br>* This group patients will receive metformin and celebrex.<br>|
| No Intervention: Empty control group<br>This group patients will not receive any postoperative adjuvant therapy. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with tumor recurrence | The 1-year tumor recurrence will be compared between the three groups | 1-year |