Clinical trial NCT03732105: Randomized Study of Adjuvant Radiotherapy After Curative Resection of HCC With Narrow Margin (RAISE)
Official title: Randomized Study of Adjuvant Radiotherapy After Curative Resection of Hepatocellular Carcinoma With Narrow Margin (≤1 cm)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Hepatocellular Carcinoma
Radiotherapy
Hepatectomy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Guangzhou Medical University
name: Southern Medical University, China
name: Shantou University Medical College
First posted: 2018-11-06
Enrollment: 148
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Recurrence Free Survival,RFS
timeFrame: two years
Secondary outcomes:
measure: Overall Survival, OS
timeFrame: two years
measure: Time To Recurrence, TTR
timeFrame: two years
measure: Incidence of Treatment-Emergent Adverse Events during the treatment period using Common Terminology Criteria for Adverse Events (CTCAE) (version 4).
timeFrame: two years
measure: health related quality of life
timeFrame: two years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: First Affiliated Hospital, Sun Yat-Sen University
name: Ming Kuang, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.