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

NCT06313190 | Recruiting Phase 2 DMC

• 1 other identifier: SL-B2024-061
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular carcinoma; Immunotherapy; Stereotactic body radiotherapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Overall survival

  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

• Local control rate (DCR)

  From date of enrollment to the date of last follow-up, assessed up to 36 months

• Treatment-related adverse events

  From date of enrollment to the date of last follow-up, assessed up to 36 months.

Other Outcomes (2)

• Correlation between serum cytokines and overall survival and immune-related adverse events

  From date of enrollment to the date of last follow-up, assessed up to 36 months

• Correlation between ctDNA and overall survival

  From date of enrollment to the date of last follow-up, assessed up to 36 months

Study Arms (2)

Arm A

EXPERIMENTAL

Patients in both cohorts will receive SBRT using volumetric arc therapy. The prescribed dose is 30-54 Gy in 3 fractions over 1 week. Then patients in the study group (arm A) will receive sintilimab as adjuvant therapy for up to 6 cycles after the completion of radiotherapy.

Radiation: Stereotactic body radiotherapy; Drug: Sintilimab

Arm B

ACTIVE COMPARATOR

Patients in both cohorts will receive SBRT using volumetric arc therapy. The prescribed dose is 30-54 Gy in 3 fractions over 1 week. Then patients in the control group (arm B) will be followed up regularly.

Radiation: Stereotactic body radiotherapy

Interventions

Stereotactic body radiotherapy RADIATION

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

Also known as: SBRT

Arm A; Arm B

Sintilimab DRUG

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.

Also known as: IBI308

Arm A

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed hepatocellular carcinoma or diagnosed by American Association for the Study of Liver Disease criteria;
• 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;
• Previous molecular targeted therapy or intravenous chemotherapy is allowed, but the interval of drug withdrawal was at least 6 months prior to protocol therapy;
• Age at diagnosis 18 to 75 years;
• Eastern Cooperative Oncology Group performance status ≤ 2
• Child-Pugh class A liver function;
• Normal liver volume greater than 700 ml;
• Estimated life expectancy ≥24 weeks;
• 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;
• Ability to understand the study and sign informed consent.

You may not qualify if:

• Patients who have previously been treated with immune checkpoint inhibitors;
• Patients with extrahepatic metastasis disease;
• A history of abdominal radiotherapy;
• Known or suspected allergy or hypersensitivity to monoclonal antibodies;
• Patients who have a preexisting or coexisting bleeding disorder;
• Female patients who are pregnant or lactating;
• Inability to provide informed consent due to psychological, familial, social and other factors;
• A history of malignancies other than hepatocellular carcinoma before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer;
• A history of diabetes for more than 10 years and poorly controlled blood glucose levels;
• Patients who cannot tolerate radiotherapy due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia;
• 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;
• A history of interstitial lung disease or non-infectious pneumonia;
• 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;
• 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);
• Any unstable situation that may endanger the safety and compliance of patients.

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Fifth Affiliated Hospital, Sun Yat-Sen University: collaborator
• Ningbo Medical Center Lihuili Eastern Hospital: collaborator

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Related Publications (4)

• 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 2018 Jan 30.

  PMID: 29366520 BACKGROUND

• 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 by immunotherapy as conversion therapy for patients with locally advanced, unresectable hepatocellular carcinoma (START-FIT): a single-arm, phase 2 trial. Lancet Gastroenterol Hepatol. 2023 Feb;8(2):169-178. doi: 10.1016/S2468-1253(22)00339-9. Epub 2022 Dec 15.

  PMID: 36529152 BACKGROUND

• 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, controlled, phase 2 trial. Nat Med. 2024 Mar;30(3):708-715. doi: 10.1038/s41591-023-02786-7. Epub 2024 Jan 19.

  PMID: 38242982 BACKGROUND

• 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, Yang Y, Chen M, Wang Y, Zhou H, Fan J; ORIENT-32 study group. Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study. Lancet Oncol. 2021 Jul;22(7):977-990. doi: 10.1016/S1470-2045(21)00252-7. Epub 2021 Jun 15.

  PMID: 34143971 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Radiosurgery; sintilimab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Mian Xi, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mian Xi, MD

CONTACT

+862087343385; ximian@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 10, 2024
• First Posted: March 15, 2024
• Study Start: April 5, 2024
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2030
• Last Updated: November 18, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)