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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT06408753
Other study ID # UW 19-857
Secondary ID
Status Completed
Phase
First received
Last updated
Start date November 1, 2019
Est. completion date March 27, 2024

Study information

Verified date May 2024
Source The University of Hong Kong
Contact n/a
Is FDA regulated No
Health authority
Study type Observational [Patient Registry]

Clinical Trial Summary

This is a prospective study to investigate the biomarkers in predicting treatment outcome and toxicity in hepatocellular carcinoma (HCC) patients receiving immune checkpoint inhibitors with or without stereotactic body radiotherapy (SBRT).


Recruitment information / eligibility

Status Completed
Enrollment 50
Est. completion date March 27, 2024
Est. primary completion date November 30, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: First Cohort (SBRT+IO): 1. Unresectable HCC confirmed by multi-disciplinary team 2. Tumor size 5-15cm 3. Number of lesion(s) = 3 4. No main portal vein or inferior vena cava thrombosis 5. ECOG performance status 0-1 6. Child-Pugh class A-B7 7. Liver volume minus gross tumor volume > 700ml 8. Adequate organ function 9. No prior systemic therapy, immunotherapy, TACE, radiotherapy, or radio-embolization Second Cohort (IO alone): 1. BCLC stage C HCC 2. ECOG performance status 0-1 3. Child-Pugh class A5-B9 4. Adequate organ function Exclusion Criteria: 1. Based on the inclusion criteria above. Any eligibility factors that do not fit the inclusion criteria will be considered as ineligible subjects.

Study Design


Related Conditions & MeSH terms


Intervention

Procedure:
sterotatic body radiotherapy
checkpoint inhibitors with or without sterotatic body radiotherapy

Locations

Country Name City State
Hong Kong Department of Clinical Oncology Hong Kong

Sponsors (1)

Lead Sponsor Collaborator
The University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

References & Publications (25)

Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Yokoi T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeno J, Wadsworth C, Melillo G, Jiang H, Huang Y, Dennis PA, Ozguroglu M; PACIFIC Investigators. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Nov 16;377(20):1919-1929. doi: 10.1056/NEJMoa1709937. Epub 2017 Sep 8. — View Citation

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Chen G, Huang AC, Zhang W, Zhang G, Wu M, Xu W, Yu Z, Yang J, Wang B, Sun H, Xia H, Man Q, Zhong W, Antelo LF, Wu B, Xiong X, Liu X, Guan L, Li T, Liu S, Yang R, Lu Y, Dong L, McGettigan S, Somasundaram R, Radhakrishnan R, Mills G, Lu Y, Kim J, Chen YH, Dong H, Zhao Y, Karakousis GC, Mitchell TC, Schuchter LM, Herlyn M, Wherry EJ, Xu X, Guo W. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature. 2018 Aug;560(7718):382-386. doi: 10.1038/s41586-018-0392-8. Epub 2018 Aug 8. — View Citation

Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009 Jan;10(1):25-34. doi: 10.1016/S1470-2045(08)70285-7. Epub 2008 Dec 16. — View Citation

Chew V, Lee YH, Pan L, Nasir NJM, Lim CJ, Chua C, Lai L, Hazirah SN, Lim TKH, Goh BKP, Chung A, Lo RHG, Ng D, Filarca RLF, Albani S, Chow PKH. Immune activation underlies a sustained clinical response to Yttrium-90 radioembolisation in hepatocellular carcinoma. Gut. 2019 Feb;68(2):335-346. doi: 10.1136/gutjnl-2017-315485. Epub 2018 Feb 13. — View Citation

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Dewan MZ, Galloway AE, Kawashima N, Dewyngaert JK, Babb JS, Formenti SC, Demaria S. Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res. 2009 Sep 1;15(17):5379-88. doi: 10.1158/1078-0432.CCR-09-0265. Epub 2009 Aug 25. — View Citation

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Harlin H, Meng Y, Peterson AC, Zha Y, Tretiakova M, Slingluff C, McKee M, Gajewski TF. Chemokine expression in melanoma metastases associated with CD8+ T-cell recruitment. Cancer Res. 2009 Apr 1;69(7):3077-85. doi: 10.1158/0008-5472.CAN-08-2281. Epub 2009 Mar 17. — View Citation

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Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J, Ayuso C, Sala M, Muchart J, Sola R, Rodes J, Bruix J; Barcelona Liver Cancer Group. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002 May 18;359(9319):1734-9. doi: 10.1016/S0140-6736(02)08649-X. — View Citation

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Wu AY, Ueda K, Lai CP. Proteomic Analysis of Extracellular Vesicles for Cancer Diagnostics. Proteomics. 2019 Jan;19(1-2):e1800162. doi: 10.1002/pmic.201800162. Epub 2019 Jan 11. — View Citation

Yang Y, Li CW, Chan LC, Wei Y, Hsu JM, Xia W, Cha JH, Hou J, Hsu JL, Sun L, Hung MC. Exosomal PD-L1 harbors active defense function to suppress T cell killing of breast cancer cells and promote tumor growth. Cell Res. 2018 Aug;28(8):862-864. doi: 10.1038/s41422-018-0060-4. Epub 2018 Jun 29. No abstract available. — View Citation

Zhang ZN, Zhu ML, Chen YH, Fu YJ, Zhang TW, Jiang YJ, Chu ZX, Shang H. Elevation of Tim-3 and PD-1 expression on T cells appears early in HIV infection, and differential Tim-3 and PD-1 expression patterns can be induced by common gamma -chain cytokines. Biomed Res Int. 2015;2015:916936. doi: 10.1155/2015/916936. Epub 2015 Jan 22. — View Citation

Zhu AX, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmer D, Verslype C, Zagonel V, Fartoux L, Vogel A, Sarker D, Verset G, Chan SL, Knox J, Daniele B, Webber AL, Ebbinghaus SW, Ma J, Siegel AB, Cheng AL, Kudo M; KEYNOTE-224 investigators. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol. 2018 Jul;19(7):940-952. doi: 10.1016/S1470-2045(18)30351-6. Epub 2018 Jun 3. Erratum In: Lancet Oncol. 2018 Sep;19(9):e440. — View Citation

* Note: There are 25 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Exosomal PD-L1 level in serum Increase in level of exosomal PD-L1 may reflect reinvigoration of T-cell activity against cancer cells, thus predicting the treatment efficacy and toxicities in HCC patients received immunotherapy with or without SBRT from the date of first study treatment to the date of last study treatment, an average of 3 years
Primary Immune profile of peripheral blood mononuclear cells (PBMC) Immune profile of pre-treatment peripheral blood is predictive of sustained responder of radio-embolization, thus predicting the treatment efficacy and toxicities in HCC patients received immunotherapy with or without SBRT from the date of first study treatment to the date of last study treatment, an average of 3 years
Secondary Serum Cytokine profile SBRT activates the host immune system, in particular those achieving clinical response to the combined treatment from the date of first study treatment to the date of last study treatment, an average of 3 years
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