Combination of Sintilimab and Stereotactic Body Radiotherapy in Advanced Metastatic HCC

NCT04547452 | Unknown Phase 2

• 1 other identifier: I-SBRT-HCC-001
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

Hepatocellular carcinoma (HCC) is a common malignancy, and more than 70% of newly diagnosed HCC patients already have advanced disease. Sorafenib and lenvatinib are recommended as first-line options for advanced HCC. The PD-1 monoclonal antibody，such as nivolumab and pembrolizumab, have been approved to treat the patients with advanced HCC by the FDA. Combining radiotherapy with immune checkpoints showed promising response rates and improved survival in several solid tumor types. The purpose of this randomized study is to determine whether stereotactic body radiation therapy (SBRT) combined with sintilimab (an anti-PD-1 antibody) will improve the response to the anticancer treatment compared to sintilimab alone in patients with advanced HCC. About 84 participants will be enrolled in this study. All will take part at West China Hospital, Sichuan University.

Conditions

Stage IV HCC; Immunotherapy; SBRT

Outcome Measures

Primary Outcomes (1)

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

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

  24 weeks after radiotherapy

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  up to 24 months after the enrollment

• Overall Survival (OS)

  up to 24 months after the enrollment

• 24-week disease control rate (DCR)

  24 weeks after radiotherapy

• Duration of response (DOR)

  up to 24 months after the enrollment

• Adverse Events

  2 years from randomization

Study Arms (2)

Sintilimab Combined with SBRT

EXPERIMENTAL

Patients will be randomly placed in either of the two arms. Participants enrolled in this arm treated to a total dose of 35-80Gy in 5-8 fractions with stereotactic radiotherapy to a liver or lung or any metastatic lesion. The choice of radiation dose will be at the discretion of the treating radiation oncologist. Sintilimab is administered intravenously at 200 mg every 3 weeks for up to 1 year.

Radiation: Stereotactic body radiation therapy; Drug: Anti-PD-1 antibody drug named Sintilimab

Sintilimab

ACTIVE COMPARATOR

Participants enrolled in this arm treated with sintilimab administered intravenously at 200 mg every 3 weeks for up to 1 year.

Drug: Anti-PD-1 antibody drug named Sintilimab

Interventions

Stereotactic body radiation therapy RADIATION

Sintilimab Combined with SBRT

Also known as: SBRT

Sintilimab Combined with SBRT

Anti-PD-1 antibody drug named Sintilimab DRUG

Sintilimab

Sintilimab; Sintilimab Combined with SBRT

Eligibility Criteria

• Age: 18 Years - 70 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;
• Deemed ineligible for curative intent therapy with surgical resection or liver transplantation.
• Estimated life expectancy ≥12 weeks;
• Male or female subjects with age: 18-70 years old
• Failure in first-line systemic treatment with sorafenib or Lenvatinib
• Unwilling to receive or unable to tolerate first-line treatment with sorafenib
• Have ECOG performance status 0-1
• Have measurable disease based on RECIST 1.1.
• Pretreatment CT chest /abdomen /pelvis within 28 days of protocol enrollment.
• Child-Pugh class A liver function (assessed within 14 days of SBRT)；
• 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 ≥ 8g/dL; d. serum albumin ≥ 3.0g/dL; e. total bilirubin ≤ 2.0×ULN, ALT, AST ≤ 5×ULN; f. serum creatinine ≤ 1.5×ULN
• Must have at least one lesion amenable to SBRT.
• Ability to understand the study and sign informed consent.

You may not qualify if:

• A history of abdominal radiotherapy;
• 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);
• 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)
• History of organ transplantation or allogeneic bone marrow transplantation，or other acquired or congenital immunodeficiency diseases
• Receipt of live, attenuated vaccine within 30 days prior to the study treatment
• Has a known history of active TB (Bacillus Tuberculosis).
• Uncontrolled intercurrent illness including, but not limited to digestive tract ulcer, uncontrolled hypertension, fracture, uncured wound, history of congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Prior invasive malignancy within 2 years except for noninvasive malignancies such as cervical carcinoma in situ, in situ prostate cancer, non-melanomatous carcinoma of the skin, lobular or ductal carcinoma in situ of the breast that has been surgically cured
• Female patients who are pregnant or lactating
• Untreated central nervous system (CNS) metastatic disease, lepto-meningeal disease, or cord compression
• Active infection requiring systemic therapy
• Presence of clinically meaningful ascites，hydrothorax or hydropericardium and patients requiring non pharmacologic intervention (eg, paracentesis) or escalation in pharmacologic intervention to maintain symptomatic control
• Severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb)

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (1)

West China Hospital

Chengdu, Sichuan, 610041, China

RECRUITING

MeSH Terms

Interventions

Radiosurgery

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

Xin Wang, PhD/MD

CONTACT

+86 28 85423609; wangxin213@sina.com

Jitao Zhou, PhD/MD

CONTACT

+86 28 85423609; zjthelen@sina.com

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: September 6, 2020
• First Posted: September 14, 2020
• Study Start: July 1, 2020
• Primary Completion: July 1, 2022
• Study Completion: July 1, 2023
• Last Updated: September 14, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)