Anti-angiogenic Agents Plus Anti-PD-1 Antibodies for uHCC
- Conditions
- Hepatocellular Carcinoma
- Interventions
- Drug: Anti-angiogenic agents plus anti-PD-1/PD-L1 antibodies
- Registration Number
- NCT04639284
- Lead Sponsor
- Shanghai Zhongshan Hospital
- Brief Summary
Combination treatment with antiangiogenic agents and anti-programmed cell death protein 1 (PD-1) antibodies have shown high anti-tumor efficacy for patients with unresectable or advanced hepatocellular carcinoma (uHCC). In this single-center cohort study, we are aiming to (1) evaluate the clinical effectiveness in real-world patients, especially for Chinese patients, most of whom were with hepatitis B virus infection; (2) predict clinical effectiveness with clinicopathological features; (3) predict clinical effectiveness with histologic features and blood samples.
- Detailed Description
Combination treatment with antiangiogenic agents and anti-programmed cell death protein 1 (PD-1) antibodies have shown high anti-tumor efficacy for patients with unresectable or advanced hepatocellular carcinoma (uHCC). In this single-center cohort study, we are aiming to:
1. To evaluate the clinical effectiveness in real-world patients, especially for Chinese patients most of whom were with hepatitis B virus infection.
2. To predict clinical effectiveness with clinicopathological features, such as lab examinations (at baseline and dynamic changes), radiological features (radiomics study at the baseline);
3. To predict clinical effectiveness with histologic features, such as PD-L1 expression, ctDNA, and peripheral immune cell subtypes.
4. To evaluate the clinical effectiveness of second- or third-line therapies, including TACE, HAIC, and interferon, for those who lost clinical benefit or who were intolerant to the combination therapy.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 200
- Documented diagnosis of HCC confirmed by histology/cytology or clinical diagnosis of HCC by Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China (2019 edition) criteria.
- Unresectable or advanced disease at the investigator's discretion. The advanced stage was BCLC C stage or China Liver Cancer Stage IIIa or IIIb.
- Child-Pugh class A or B7.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- Subjects received combination therapy with an anti-angiogenic agent and an anti-PD-1/PD-L1 antibody, received at least one imaging evaluation, and signed an Informed Consent Form. Anti-angiogenic agents include sorafenib, lenvatinib, apatinib, and bevacizumab; anti-PD-1/PD-L1 antibodies include pembrolizumab, nivolumab, sintilimab, toripalimab, camrelizumab, tislelizumab, and atezolizumab.
- Adequate hematologic and end-organ function.
- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
- History of malignancy other than HCC within 5 years prior to the therapy, with the exception of adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or papillary thyroid carcinoma.
- History of organ transplantation or hepatic encephalopathy.
- Allergic to anti-angiogenic agents or anti-PD-1/PD-L1 agents.
- History of gastrointestinal perforation and/or fistula within the 6 months, a history of intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection, Crohn's disease, ulcerative colitis, or chronic diarrhea within 6 months.
- Active autoimmune disease requiring systemic therapy within 2 years prior to the first dose, allowing the use of alternative therapies (e.g., thyroxine, insulin, or physiologic corticosteroids for adrenal or pituitary insufficiency); history of primary immunodeficiency; presence of only autoimmune antibody-positive subjects. The presence of autoimmune disease needs to be confirmed at the investigator's discretion.
- Uncontrollable hypertension, SBP >140 mmHg or DBP >90 mmHg after optimal medical therapy, hypertensive crisis, or history of hypertensive encephalopathy.
- Subjects had a bleeding event in the past 6 months due to esophageal or gastric fundus varices induced by portal venous hypertension; subjects have undergone a gastrointestinal endoscopy within 3 months prior to the first dose to diagnose the presence of severe (G3) varices; subjects had a high risk of bleeding as assessed by the investigator.
- Subject requests withdrawal of informed consent.
- Other conditions that the investigator deems inappropriate for participation in this study.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Combinational therapy Anti-angiogenic agents plus anti-PD-1/PD-L1 antibodies Participants who receive systemic treatment with an anti-angiogenic agent, including sorafenib, lenvatinib, apatinib, and bevacizumab, in combination with an anti-PD-1/PD-L1 antibody, including pembrolizumab, nivolumab, sintilimab, toripalimab, camrelizumab, tislelizumab, and atezolizumab.
- Primary Outcome Measures
Name Time Method Objective response up to 2 years Subjects with complete response or partial response
- Secondary Outcome Measures
Name Time Method Duration of response up to 2 years the interval between the time of partial or complete response to the time of progressive disease
Time to deterioration in patient-reported quality of life, physical functioning, and role functioning up to 2 years Quality of life, physical functioning, and role functioning was determined by EORTC QLQ-C30 and QLQ-HCC18 questionnaires.
Progression free survival up to 2 years the interval between the time of treatment initiation to the time of progressive disease or patient death
Overall survival up to 2 years the interval between the time of treatment initiation to the time of patient death
Ratio of R0 resection up to 2 years The ratio of patients who underwent R0 resection to patients received combination therapy
Recurrence-free survival up to 5 years the interval between the time of surgical resection to the time of disease recurrence or patient death for those who underwent surgery
Trial Locations
- Locations (1)
Zhongshan Hospital, Fudan University
🇨🇳Shanghai, Shanghai, China