Combination of SBRT and Immunotherapy in Small Hepatocellular Carcinoma (HSBRT2402)

Hepatocellular Carcinoma Clinical Trial

— HSBRT2402  

Official title:

Stereotactic Body Radiotherapy With or Without Adjuvant Immunotherapy for Small Hepatocellular Carcinoma: An Open-label, Randomized, Phase II Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06313190
• Other study ID #: SL-B2024-061
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: April 5, 2024
• Est. completion date: April 30, 2030

Study information

• Verified date: March 2024
• Source: Sun Yat-sen University
• Contact: Mian Xi, MD
• Phone: +862087343385
• Email: ximian[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

For inoperable small hepatocellular carcinoma (HCC), stereotactic body radiotherapy (SBRT) is an effective and safe local treatment. Despite satisfactory local control rate, the incidence of recurrence out the field remains substantial, with 2-year PFS of 31.9% to 60.9%. Therefore, a more effective treatment mode is urgently needed. Immune checkpoint inhibitors targeting PD-1/PD-L1 have shown substantial clinical benefits in advanced HCC as well as resected high-risk HCC. Recently, the combination of immunotherapy with SBRT has shown promising activity in HCC, but its utility in small HCC is unclear. The aim of this study was to investigate the efficacy and safety of SBRT followed by sintilimab (an anti-PD-1 antibody) in patients with recurrent or residual small HCC.

Description:

A total of 140 patients with recurrent or residual small HCC will be stratified according to tumor diameter (≤3 vs. >3 cm) and tumor type (recurrent vs. residual) and randomly assigned (1:1) to receive stereotactic body radiotherapy (SBRT) with or without adjuvant sintilimab for 6 cycles (200 mg, once every 3 weeks, with the first dose within 1 week after the completion of SBRT).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 140
• Est. completion date: April 30, 2030
• Est. primary completion date: April 30, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Histologically confirmed hepatocellular carcinoma or diagnosed by American Association for the Study of Liver Disease criteria;

2. Presence of recurrent or residual HCC lesions without vascular invasion or extrahepatic metastasis confirmed by CT or MRI, the sum of the maximum diameter of lesions =5 cm, total number of lesions were =2, and at least one of which is measurable according to the RECIST 1.1 Criteria;

3. Previous molecular targeted therapy or intravenous chemotherapy is allowed, but the interval of drug withdrawal was at least 6 months prior to protocol therapy;

4. Age at diagnosis 18 to 75 years;

5. Eastern Cooperative Oncology Group performance status = 2

6. Child-Pugh class A liver function;

7. Normal liver volume greater than 700 ml;

8. Estimated life expectancy =24 weeks;

9. The function of important organs meets the following requirements: a. white blood cell count (WBC) = 3.0×109/L, absolute neutrophil count (ANC) = 1.5×109/L; b. platelets = 50×109/L; c. hemoglobin = 9g/dL; d. serum albumin = 2.8g/dL; e. total bilirubin = 1.5×ULN, ALT, AST and/or AKP = 2.5×ULN; f. serum creatinine = 1.5×ULN or creatinine clearance rate >60 mL/min;

10. Ability to understand the study and sign informed consent.

Exclusion Criteria:

1. Patients who have previously been treated with immune checkpoint inhibitors;

2. Patients with extrahepatic metastasis disease;

3. A history of abdominal radiotherapy;

4. Known or suspected allergy or hypersensitivity to monoclonal antibodies;

5. Patients who have a preexisting or coexisting bleeding disorder;

6. Female patients who are pregnant or lactating;

7. Inability to provide informed consent due to psychological, familial, social and other factors;

8. A history of malignancies other than hepatocellular carcinoma before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer;

9. A history of diabetes for more than 10 years and poorly controlled blood glucose levels;

10. Patients who cannot tolerate radiotherapy due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia;

11. Active autoimmune diseases, a history of autoimmune diseases (including but not limited to these diseases or syndromes, such as colitis, hepatitis, hyperthyroidism), a history of immunodeficiency (including a positive HIV test result), or other acquired or congenital immunodeficiency diseases, a history of organ transplantation or allogeneic bone marrow transplantation;

12. A history of interstitial lung disease or non-infectious pneumonia;

13. A history of active pulmonary tuberculosis infection within 1 year or a history of active pulmonary tuberculosis infection more than 1 year ago but without formal anti-tuberculosis treatment;

14. Presence of active hepatitis B (HBV DNA = 2000 IU/mL or 104 copies/mL), hepatitis C (positive for hepatitis C antibody, and HCV-RNA levels higher than the lower limit of the assay);

15. Any unstable situation that may endanger the safety and compliance of patients.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Radiation:
• Stereotactic body radiotherapy
Patients in both cohorts will receive SBRT using volumetric arc therapy. The prescribed dose is 30-54 Gy in 3 fractions over 1 week.

Drug:
• Sintilimab
Patients received sintilimab 200 mg every 3 weeks for up to 6 cycles, with the first dose within 1 week after the completion of SBRT.

Locations

Country	Name	City	State
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (3)

Lead Sponsor	Collaborator
Sun Yat-sen University	Fifth Affiliated Hospital, Sun Yat-Sen University, Ningbo Medical Center Lihuili Eastern Hospital

Country where clinical trial is conducted

China, 

References & Publications (4)

Chiang CL, Chiu KWH, Chan KSK, Lee FAS, Li JCB, Wan CWS, Dai WC, Lam TC, Chen W, Wong NSM, Cheung ALY, Lee VWY, Lau VWH, El Helali A, Man K, Kong FMS, Lo CM, Chan AC. Sequential transarterial chemoembolisation and stereotactic body radiotherapy followed b — View Citation

Kim HJ, Park S, Kim KJ, Seong J. Clinical significance of soluble programmed cell death ligand-1 (sPD-L1) in hepatocellular carcinoma patients treated with radiotherapy. Radiother Oncol. 2018 Oct;129(1):130-135. doi: 10.1016/j.radonc.2017.11.027. Epub 201 — View Citation

Ren Z, Xu J, Bai Y, Xu A, Cang S, Du C, Li Q, Lu Y, Chen Y, Guo Y, Chen Z, Liu B, Jia W, Wu J, Wang J, Shao G, Zhang B, Shan Y, Meng Z, Wu J, Gu S, Yang W, Liu C, Shi X, Gao Z, Yin T, Cui J, Huang M, Xing B, Mao Y, Teng G, Qin Y, Wang J, Xia F, Yin G, Yan — View Citation

Wang K, Xiang YJ, Yu HM, Cheng YQ, Liu ZH, Qin YY, Shi J, Guo WX, Lu CD, Zheng YX, Zhou FG, Yan ML, Zhou HK, Liang C, Zhang F, Wei WJ, Lau WY, Li JJ, Liu YF, Cheng SQ. Adjuvant sintilimab in resected high-risk hepatocellular carcinoma: a randomized, contr — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Correlation between serum cytokines and overall survival and immune-related adverse events	The correlation between dynamic change of serum cytokines (IL-2R, IL-6, IL-13, IL-8, CCL3, CD40, and CD274) during treatment and survival outcomes and immune-related adverse events.	From date of enrollment to the date of last follow-up, assessed up to 36 months
Other	Correlation between ctDNA and overall survival	The correlation between dynamic change of ctDNA (before and after treatment) and survival outcomes.	From date of enrollment to the date of last follow-up, assessed up to 36 months
Primary	Progression-free survival (PFS) rate	Two-year follow-up from the date of enrollment to the date of disease progression or last follow-up	From date of enrollment until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 24 months
Secondary	Overall survival	Three-year follow-up from the enrollment to the date of death from any cause or date of lost follow-up	From date of enrollment until the date of death from any cause or the date of last follow-up, whichever came first, assessed up to 36 months
Secondary	Local control rate (DCR)	The proportion of patients with complete response, partial response, or stable disease for the target lesion according to RECIST criteria.	From date of enrollment to the date of last follow-up, assessed up to 36 months
Secondary	Treatment-related adverse events	Incidence of treatment-related adverse events as assessed by CTCAE v4.0.	From date of enrollment to the date of last follow-up, assessed up to 36 months.