Clinical trial NCT02678013: RFA+Highly-purified CTL vs. RFA Alone for Recurrent HCC
Official title: Radiofrequency Ablation Combined With Highly-purified CTL vs. Radiofrequency Ablation Alone for Recurrent HCC
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Hepatocellular Carcinoma
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2016-02-09
Enrollment: 210
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: TREATMENT

Brief summary: Hepatocellular carcinoma (HCC) is the fifth most common and the third leading cause of cancer-related death worldwide. Recurrence of tumor within the liver remnant is common, with a reported 5-year recurrence rate of 70%. Repeat hepatectomy is an effective treatment for intrahepatic HCC but with a small proportion of resection rate because of the poor functional liver reserve and postoperative complications. Radiofrequency ablation(RFA) is becoming the main effective treatment for small HCC (≤5.0cm). The efficacy of RFA for recurrent HCC has been reported to be comparable to those achieved by surgery with minimal, but higher local recurrence rate after RFA. It has been reported that immunotherapy in patients who underwent curative treatment for HCC, adjuvant immunotherapy with activated CIK cells increased recurrence-free and overall survival. But there is little evidence for adjuvant immunotherapy of recurrence HCC. Cytotoxic T lymphocytes(CTL), a kind of effective T cells that specific recognizing and killing antigen targeted cells through cloning amplification after receiving antigen information from antigen presented cell and playing key role to clear cancerous cells. So our hypothesis is that RFA combined with immunotherapy (Highly-purified CTL) is superior to RFA for recurrent HCC. The aim of this prospective study is to compare the outcome of RFA combined with immunotherapy (Highly-purified CTL) with RFA for small recurrent HCC after partial hepatectomy.


Eligibility criteria: Inclusion Criteria:

1. age 18-75 years;
2. recurrence of HCC 12 months after initial hepatectomy;
3. no other treatment received except for the initial hepatectomy;
4. single tumor≤5.0cm in diameter; or 2-3 lesions each≤3.0cm;
5. lesions visible on ultrasound and with an acceptable and safe path between the lesion and the skin as shown on ultrasound;
6. no severe coagulation disorders (prothrombin activity\<40% or a platelet count\<40,000/mm3);
7. Eastern Co-operative Oncology Group performance(ECOG) status 0-1.

Exclusion Criteria:

1. Pregnant women, breastfeeding women or plan pregnancy for the future 2 years;
2. The presence of vascular invasion or extrahepatic spread onimaging;
3. Usage of strong immunosuppressive agents such as corticosteroids, cyclosporine A within six months or longer;
4. HIV antibody or HCV antibody positive;
5. Immunodeficiency diseases or autoimmune diseases (such as rheumatoid arthritis, Buerger's disease, multiple sclerosis and type 1 diabetes);
6. Suffering with cancers (except skin cancer, prostate cancer or cervical carcinoma in situ) at the enrolling time or 5 years before;
7. Suffering with other organ failure;
8. Suffering with severe mental illness;
9. Drug addiction (including alcohol) for 1 year before the enrolling time;
10. Participate in other Clinical trials within three months prior to 3 months before the enrolling time;
11. Other researchers believe that the patient is not fit for inclusion.

Primary outcomes:
measure: Recurrence-free survival
timeFrame: 2 years
Secondary outcomes:
measure: Overall survival
timeFrame: 5 years
measure: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0
timeFrame: 1 month
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Zhen-Wei Peng
state: Guangdong
Study officials:
affiliation: First Affiliated Hospital, Sun Yat-Sen University
name: Ming Kuang, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bruix J, Sherman M; American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology. 2011 Mar;53(3):1020-2. doi: 10.1002/hep.24199. No abstract available.
citation: Lee JH, Lee Y, Lee M, Heo MK, Song JS, Kim KH, Lee H, Yi NJ, Lee KW, Suh KS, Bae YS, Kim YJ. A phase I/IIa study of adjuvant immunotherapy with tumour antigen-pulsed dendritic cells in patients with hepatocellular carcinoma. Br J Cancer. 2015 Dec 22;113(12):1666-76. doi: 10.1038/bjc.2015.430. Epub 2015 Dec 10.
citation: Harding JJ, El Dika I, Abou-Alfa GK. Immunotherapy in hepatocellular carcinoma: Primed to make a difference? Cancer. 2016 Feb 1;122(3):367-77. doi: 10.1002/cncr.29769. Epub 2015 Nov 5.