Preventive Effect of Celecoxib on Sorafenib-related Hand Foot Syndrome, a Single Center, Randomized Controlled Clinical Trail

Preventive Effect of Celecoxib on Sorafenib-related Hand Foot Syndrome

Hepatocellular carcinoma (HCC) is a common fatal malignant tumor, although with the popularity of health examination, most patients were diagnosed as HCC in advanced stages so far. Sorafenib is currently recognized worldwide as the only effective treatment for advanced HCC. However, sorafenib need long-term medication, and will bring a series of side effects, including, hand, foot and comprehensive syndrome (Hand-foot syndrome, HFS) limbs swelling, rash, peeling, pain.Occurrence rate of HFS is about 21%-51%, which seriously affect patient's quality of life.Besides, this side effects appeared to be dose-related.When severe HFS happened, sorafenib need to reduce dosage or discontinue administration, which could seriously affect the patient's survival. Therefore, investigators designed this prospective randomized controlled study to explore preventive effect of celecoxib for sorafenib related HFS, the influence on the quality of life in patients with, and also the synergistic anti-tumor effect of celecoxib in combination with sorafenib on HCC. This study will explore horizon of improving treatment for sorafenib in patients with advanced HCC,quality of life and tumor control.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Celecoxib; Drug: Sorafenib

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1.Diagnosed with HCC according to the Primary liver cancer diagnosis and treatment practices published by the Ministry of Health in 2011 China
• 2.A Karnofsky Performance Status (KPS) score ≥70 points
• 3.Age between 18 and 70 years
• 4.Child-Pugh classA or B (class B patients had scores no greater than 7 points). In addition, the baseline laboratory tests had to meet the following criteria: white blood cells (WBCs) ≥1.5 × 109/L, platelets ≥50 × 109/L, hemoglobin ≥80 g/L, serum aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2 x the upper limit of normal (ULN), serum creatinine ≤ 1.5 x ULN, an international normalized ratio (INR)<1.5 or prothrombin time < the ULN + 4 seconds, albumin ≥30 g/L, and total bilirubin ≤34mmol/L
• 5.Patients with advanced hepatocellular carcinoma who failed first-line therapy with surgery，radiofrequency ablation

Exclusion Criteria:

• 1.Pugh Child-Pugh Grade C, or with massive ascites or had a history of hepatic encephalopathy, or previous history of gastrointestinal bleeding
• 2.Poor general condition or cachexia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Celecoxib group; Patients were treated with sorafenib taking capsules celecoxib (Celebrex) at the same time, 200mg/day, last 6 months	Drug: Celecoxib; Patients from experimental group will take celecoxib, except for sorafenib; Drug: Sorafenib; Each group will receive sorafenib as basic treatment.
Active Comparator: Control group; Patients take sorafenib only.	Drug: Sorafenib; Each group will receive sorafenib as basic treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of participants with clinically definite Sorafenib-related Hand Foot Syndrome	within the first 6 months after sorafenib administration

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	one year

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Minshan Chen, Sun Yat-sen University

Publications and helpful links

General Publications

• Chen JC, Wang JC, Pan YX, Yi MJ, Chen JB, Wang XH, Fu YZ, Zhang YJ, Xu L, Chen MS, Zhang RX, Zhou ZG. Preventive effect of celecoxib in sorafenib-related hand-foot syndrome in hepatocellular carcinoma patients, a single-center, open-label, randomized, controlled clinical phase III trial. Am J Cancer Res. 2020 May 1;10(5):1467-1476. eCollection 2020.

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: November 6, 2016
• First Submitted That Met QC Criteria: November 8, 2016
• First Posted (Estimate): November 11, 2016

Study Record Updates

• Last Update Posted (Actual): September 10, 2019
• Last Update Submitted That Met QC Criteria: September 7, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: hepatocellular carcinoma; celecoxib; sorafenib
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Dermatitis; Drug-Related Side Effects and Adverse Reactions; Drug Eruptions; Drug Hypersensitivity; Carcinoma, Hepatocellular; Hand-Foot Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Cyclooxygenase 2 Inhibitors; Sorafenib; Celecoxib
• Other Study ID Numbers: 2016-FXY-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO