Actively Recruiting
Sintilimab Combined With Bevacizumab Biosimilar as Adjuvant Treatment After Resection of Ruptured Hepatocellular Carcinoma (CLEAR-2)
Led by Ruijin Hospital · Updated on 2026-03-27
35
Participants Needed
4
Research Sites
175 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Primary liver cancer-particularly hepatocellular carcinoma (HCC)-remains a major health burden in China, characterized by high incidence and mortality rates and poor 5-year survival. Spontaneous rupture of HCC (SRHCC), although a relatively uncommon complication, is associated with extremely high mortality and marked geographic variation, with disproportionately higher incidence and rupture-related deaths reported in Asian populations. For patients with preserved liver function and resectable tumors, hepatic resection can offer favorable long-term survival and even a potential cure. However, despite surgical removal, the risk of postoperative recurrence is substantially increased, and long-term outcomes remain unsatisfactory. Currently, there is no validated adjuvant therapy to reduce recurrence or improve survival after resection. In recent years, immune checkpoint inhibitors (ICIs) in combination with anti-angiogenic agents have demonstrated synergistic antitumor activity and manageable safety in advanced HCC. Notably, studies of sintilimab plus a bevacizumab biosimilar have shown significant improvements in overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Moreover, emerging evidence in the adjuvant and perioperative settings suggests that PD-1 blockade may delay recurrence in high-risk patients, such as those with microvascular invasion. Based on the high postoperative recurrence rate in SRHCC patients and the existing therapeutic gap, along with established evidence of the efficacy of immune checkpoint inhibitors combined with antiangiogenic therapy in advanced HCC, conducting a prospective Phase II single-arm study of adjuvant therapy with sintilimab plus the bevacizumab biosimilar holds significant clinical and scientific value. This study aims to evaluate the tolerability of this combination regimen in postoperative SRHCC patients at high risk of recurrence. It is expected to provide a more effective treatment option for patients diagnosed with spontaneously ruptured hepatocellular carcinoma, improve their prognosis, and offer scientific evidence for future treatment strategies.
CONDITIONS
Official Title
Sintilimab Combined With Bevacizumab Biosimilar as Adjuvant Treatment After Resection of Ruptured Hepatocellular Carcinoma (CLEAR-2)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Patients provide written informed consent before any study procedures
- Age between 18 and 75 years, any gender
- Spontaneous tumor rupture with bleeding confirmed by imaging before or during surgery
- Clinical history of abdominal pain within 2 weeks before surgery if rupture was found incidentally during surgery
- Chinese Liver Cancer (CNLC) stage I or II
- Complete surgical removal of tumor with negative margins and intraoperative irrigation of at least 5000 mL of distilled water or saline
- Complete response confirmed by imaging 4 to 8 weeks after surgery
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Child-Pugh class A with a score of 6 or less
- Life expectancy of at least 12 months
- Specific laboratory test values within 3 days before first dose including neutrophil count, platelet count, hemoglobin, serum albumin, bilirubin, liver enzymes, creatinine, coagulation parameters, and urine protein
- For patients with hepatitis B virus infection, viral DNA must be controlled below 2000 IU/mL with antiviral therapy started at least 1 week before treatment
- Female patients of childbearing potential must have a negative pregnancy test before first dose
- Patients and partners of childbearing potential must agree to use effective contraception during treatment and for 6 months after last dose
You will not qualify if you...
- Diagnosis of liver cancers other than hepatocellular carcinoma, including cholangiocarcinoma or combined types
- Use of chemotherapeutic agents during surgery lavage
- Child-Pugh class B or C
- ECOG performance status above 1
- Evidence of cancer spread outside the liver or residual disease after surgery
- Prior systemic cancer treatments including targeted, immune, investigational drugs, or local therapies like TACE (except preoperative TAE for bleeding control)
- Moderate or severe ascites needing drainage or high ascites score, or uncontrolled pleural or pericardial effusions
- Current or history of serious lung diseases affecting immune-related lung toxicity diagnosis
- Active pneumonia or severe lung function impairment
- Active tuberculosis infection
- Active autoimmune diseases or history of autoimmune diseases likely to recur, except certain controlled conditions
- Use of immunosuppressive drugs or corticosteroids above specified doses within 2 weeks before treatment
- Recent or high risk of gastrointestinal bleeding or related conditions
- Known bleeding or clotting disorders or current full-dose anticoagulant use
- Recent blood clot or embolic events within 6 months
- Significant heart diseases including heart failure, unstable angina, recent heart attack, serious arrhythmias, or abnormal QTc intervals
- Poorly controlled high blood pressure or history of hypertensive crisis
- Major vascular disease requiring surgery or recent arterial thrombosis
- Severe wounds, ulcers, or unhealed fractures
- Problems swallowing or absorbing medications
- Severe infections within 4 weeks before treatment or recent antibiotic use for infection
- Known immunodeficiency such as HIV
- Vaccination with live vaccines within 28 days before treatment or expected need during study
- Any other condition that may impair study results, patient safety, or cause early study withdrawal including substance abuse or severe illnesses
AI-Screening
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Trial Site Locations
Total: 4 locations
1
Sanming First Hospital
Sanming, Fujian, China, 365000
Not Yet Recruiting
2
The Third Bethune Hospital of Jilin University
Changchun, Jilin, China, 130033
Actively Recruiting
3
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, China, 200025
Actively Recruiting
4
Huashan Hospital, Fudan University
Shanghai, Shanghai Municipality, China, 200031
Actively Recruiting
Research Team
Y
Yongjun Chen
CONTACT
F
Feng Ye
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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