Combination of Sintilimab and Stereotactic Body Radiotherapy in Hepatocellular Carcinoma (ISBRT01)

NCT04167293 | Unknown Phase 2

• 1 other identifier: B2019-108-01
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief Summary

Although sorafenib is the standard treatment for hepatocellular carcinoma with portal vein invasion, the outcome of these patients remains very poor, with a median survival time of 5.5 to 7.2 months. It has been demonstrated that first-line treatment with transarterial chemoembolization plus radiotherapy could provide more favorable survival than sorafenib alone. However, intrahepatic dissemination and distant metastasis remains the major recurrence pattern after treatment in these patients; therefore, searching for new strategies to improve efficacy is necessary. Immunotherapy targeting the PD-1/PD-L1 checkpoints has demonstrated promising activity in advanced HCC. Combining radiotherapy with immune checkpoints showed promising response rates and improved survival in several solid tumor types. The aim of this randomized study was to investigate the efficacy and safety of stereotactic body radiotherapy followed by sintilimab (an anti-PD-1 antibody) compared with stereotactic body radiotherapy alone for hepatocellular carcinoma with portal vein invasion after arterially directed therapy.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular carcinoma; immunotherapy; PD-1; stereotactic body radiotherapy

Outcome Measures

Primary Outcomes (1)

• 24-week progression-free survival (PFS) rate

  The proportion of patients with progression disease according to mRECIST at 24 weeks from randomization.

  24 weeks after radiotherapy

Secondary Outcomes (6)

• Progression-free survival (PFS)

  2 years from randomization

• Overall survival (OS)

  2 years from randomization

• 24-week overall response rate (ORR)

  24 weeks after radiotherapy

• 24-week disease control rate (DCR)

  24 weeks after radiotherapy

• Duration of response (DOR)

  2 years from randomization

Study Arms (2)

SBRT + PD-1 Arm

EXPERIMENTAL

Patients assigned to this arm will receive SBRT followed by sintilimab. Patients will receive stereotactic body radiotherapy (SBRT) using volumetric arc therapy. The prescribed dose is 30-54 Gy in 3-6 fractions over 1-2 weeks. In the SBRT + PD-1 arm, sintilimab is administered intravenously at 200 mg every 3 weeks for up to 1 year. The first course of sintilimab will be given within 4-6 weeks after completion of SBRT.

Radiation: stereotactic body radiotherapy; Drug: Sintilimab

SBRT Arm

OTHER

Patients assigned to this arm will receive SBRT alone. Patients will receive stereotactic body radiotherapy (SBRT) using volumetric arc therapy. The prescribed dose is 30-54 Gy in 3-6 fractions over 1-2 weeks.

Radiation: stereotactic body radiotherapy

Interventions

stereotactic body radiotherapy RADIATION

Patients will receive stereotactic body radiotherapy (SBRT) using volumetric arc therapy. The prescribed dose is 30-54 Gy in 3-6 fractions over 1-2 weeks.

Also known as: SBRT

SBRT + PD-1 Arm; SBRT Arm

Sintilimab DRUG

Sintilimab is administered intravenously at 200 mg every 3 weeks for up to 1 year. The first course of sintilimab will be given within 4-6 weeks after completion of SBRT.

Also known as: IBI308

SBRT + PD-1 Arm

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;
• No previous treatment for hepatocellular carcinoma, and received arterially directed therapy (transarterial chemoembolization or hepatic arterial infusion chemotherapy) as initial treatment and achieved technical success;
• Absence of extrahepatic metastasis disease;
• Portal vein invasion (at least the first- or second-branch portal vein) confirmed by 2 imaging techniques;
• Less than 3 active intrahepatic lesions with a total diameter of less than 15 cm were required, at least one of which is measurable according to the mRECIST Criteria;
• 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 ≥12 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 been treated previously with systemic anti-tumor therapy (including chemotherapy, molecule-targeted therapy, immunotherapy, etc.);
• Patients with extrahepatic metastasis disease at diagnosis;
• The total diameter of the active intrahepatic lesions was more than 15 cm;
• 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);

Sponsors & Collaborators

• Mian XI: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Related Publications (3)

• Shi Y, Su H, Song Y, Jiang W, Sun X, Qian W, Zhang W, Gao Y, Jin Z, Zhou J, Jin C, Zou L, Qiu L, Li W, Yang J, Hou M, Zeng S, Zhang Q, Hu J, Zhou H, Xiong Y, Liu P. Safety and activity of sintilimab in patients with relapsed or refractory classical Hodgkin lymphoma (ORIENT-1): a multicentre, single-arm, phase 2 trial. Lancet Haematol. 2019 Jan;6(1):e12-e19. doi: 10.1016/S2352-3026(18)30192-3.

  PMID: 30612710 RESULT

• Shen L, Xi M, Zhao L, Zhang X, Wang X, Huang Z, Chen Q, Zhang T, Shen J, Liu M, Huang J. Combination Therapy after TACE for Hepatocellular Carcinoma with Macroscopic Vascular Invasion: Stereotactic Body Radiotherapy versus Sorafenib. Cancers (Basel). 2018 Dec 14;10(12):516. doi: 10.3390/cancers10120516.

  PMID: 30558224 RESULT

• Yoon SM, Ryoo BY, Lee SJ, Kim JH, Shin JH, An JH, Lee HC, Lim YS. Efficacy and Safety of Transarterial Chemoembolization Plus External Beam Radiotherapy vs Sorafenib in Hepatocellular Carcinoma With Macroscopic Vascular Invasion: A Randomized Clinical Trial. JAMA Oncol. 2018 May 1;4(5):661-669. doi: 10.1001/jamaoncol.2017.5847.

  PMID: 29543938 RESULT

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: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 15, 2019
• First Posted: November 18, 2019
• Study Start: November 16, 2019
• Primary Completion: November 30, 2021
• Study Completion: October 31, 2022
• Last Updated: March 23, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)