Randomized Study of Adjuvant Radiotherapy After Curative Resection of HCC With Narrow Margin (RAISE) (RAISE)

Randomized Study of Adjuvant Radiotherapy After Curative Resection of Hepatocellular Carcinoma With Narrow Margin (≤1 cm)

RAISE is a multicenter randomized controlled trial to assess the efficacy of adjuvant radiotherapy for controlling postsurgical recurrence in HCC patients with narrow margin (≤ 1 cm) after curative resection.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma; Hepatectomy; Radiotherapy
• Intervention / Treatment: Radiation: Surgery-radiotherapy

Detailed Description

RAISE trial will recruit 148 patients, and they will be randomized (1:1) to two groups (the surgery group and the surgery-radiotherapy group). Random assignment was stratified by the condition of MVI and tumor size. All patients in the surgery-radiotherapy group received Intensity Modulated Radiation Therapy (IMRT) within 1-3 months after surgical resection. The prescription dose was planned at 50 gray in 25 fractions over 5-6 weeks. The trial is to verify whether adjuvant radiotherapy prolongs recurrence-free survival in patients with a narrow resection margin.

• Study Type: Interventional
• Enrollment (Estimated): 148
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ming Kuang, PhD; Phone Number: 8576 008687755766; Email: kuangm@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • The First Affiliated Hospital of Sun Yat-sen University
      • Contact: Ming Kuang, Ph.D.; Phone Number: 8576 008687755766; Email: kuangm@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18 - 75 years.
2. HCC who underwent R0 resection with pathological confirmation.
3. The narrowest margin is less than or equal to 1 cm.
4. No residual tumors after surgery based on postoperative CT or MR images in 4-6 weeks.
5. ECOG PS ≤ 1.
6. Child-Pugh score 5-7.
7. Expected life expectancy ≥ 6 months.
8. Blood, liver, and kidney functions meet the following criteria: 1)Neutrophil counts ≥ 1.5×109/L; 2)Platelet counts ≥ 60×109/L; 3)Hemoglobin concentration ≥ 90g/L; 4)Serum albumin concentration ≥ 30g/L; 5)Bilirubin ≤ 1.5 × upper limit of normal; 6)AST and ALT < 3× ULN; 7)Extended prothrombin time not exceeding 3s of ULN; 8)Creatinine < 1.5× ULN.

Exclusion Criteria:

1. Preoperative imaging revealed tumor thrombus in the portal vein, hepatic vein, bile duct, or extrahepatic metastasis.
2. The number of tumors ≥4.
3. Pregnant or lactating women or subjects scheduled for contraceptive procedures within 2 years.
4. Patients with concomitant HIV or syphilis infection.
5. Patients with concurrent or other malignancies within 5 years before enrollment.
6. Patients receiving allogeneic organ transplantation.
7. Patients with severe dysfunction of the heart, kidneys or other organs.
8. Participated in clinical trials of other drugs within 12 months before enrollment.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Surgery-radiotherapy; Patients in the surgery-radiotherapy group will receive Intensity Modulated Radiation Therapy (IMRT) at a dose of 50Gy/25fraction after surgery. After radiotherapy, patients will be actively monitored.	Radiation: Surgery-radiotherapy; Patients in the surgery-radiotherapy group will receive Intensity Modulated Radiation Therapy (IMRT) at a dose of 50Gy/25fraction after randomization.
No Intervention: Surgery group; Patients in the surgery group will be actively monitored after randomization.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence Free Survival,RFS	Defined as the time from randomization until disease recurrence or death from any cause, whichever happens first.	two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
health related quality of life	The quality of life is accessed by EORTC QLQ-C30 (version 3).	two years
Overall Survival, OS	Defined as the time from randomization until death from any cause.	two years
Time To Recurrence, TTR	Defined as the time from randomization until disease recurrence.	two years
Incidence of Treatment-Emergent Adverse Events during the treatment period using Common Terminology Criteria for Adverse Events (CTCAE) (version 4).	Incidence of Treatment-Emergent Adverse Events during the treatment period using Common Terminology Criteria for Adverse Events (CTCAE) (version 4)causality of Adverse Events (AEs) during the treatment period using Common Terminology Criteria for Adverse Events (CTCAE) (version 4).	two years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Southern Medical University, China; Shantou University Medical College; Guangzhou Medical University
• Investigators: Principal Investigator: Ming Kuang, PhD, First Affiliated Hospital, Sun Yat-Sen University

Publications and helpful links

General Publications

• Rodriguez-Peralvarez M, Luong TV, Andreana L, Meyer T, Dhillon AP, Burroughs AK. A systematic review of microvascular invasion in hepatocellular carcinoma: diagnostic and prognostic variability. Ann Surg Oncol. 2013 Jan;20(1):325-39. doi: 10.1245/s10434-012-2513-1. Epub 2012 Nov 13.
• Wang WH, Wang Z, Wu JX, Zhang T, Rong WQ, Wang LM, Jin J, Wang SL, Song YW, Liu YP, Ren H, Fang H, Wang WQ, Liu XF, Yu ZH, Li YX. Survival benefit with IMRT following narrow-margin hepatectomy in patients with hepatocellular carcinoma close to major vessels. Liver Int. 2015 Dec;35(12):2603-10. doi: 10.1111/liv.12857. Epub 2015 Jun 3.
• Yu W, Wang W, Rong W, Wang L, Xu Q, Wu F, Liu L, Wu J. Adjuvant radiotherapy in centrally located hepatocellular carcinomas after hepatectomy with narrow margin (<1 cm): a prospective randomized study. J Am Coll Surg. 2014 Mar;218(3):381-92. doi: 10.1016/j.jamcollsurg.2013.11.030. Epub 2013 Dec 2.

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2018
• Primary Completion (Estimated): August 11, 2025
• Study Completion (Estimated): August 11, 2025

Study Registration Dates

• First Submitted: November 4, 2018
• First Submitted That Met QC Criteria: November 4, 2018
• First Posted (Actual): November 6, 2018

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Apatinib; Angiogenesis Inhibitors
• Other Study ID Numbers: 2018175

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No