Trial Title:
Adjuvant Adebrelimab Plus Apatinib for Participants With HCC at High-risk of Recurrence After Curative Resection
NCT ID:
NCT06454578
Condition:
Carcinoma, Hepatocellular
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Recurrence
Apatinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Adebrelimab + Apatinib
Description:
the first 6 months or 8 cycles: Adebrelimab 1200 mg, every 3 weeks； Apatinib 250 mg/day
Maintenance phase： Adebrelimab 1200 mg, every 3 weeks, Maximum maintenance up to 2 years
Arm group label:
Adebrelimab + Apatinib
Summary:
This is a single-center, single-arm, open-label clinical study to evaluate the efficacy
and safety of Adebrelimab plus Apatinib as adjuvant therapy in hepatocellular carcinoma
(HCC) participants who are at high risk of recurrence after curative resection.
Detailed description:
Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality.
Surgical resection is the most important radical treatment. However, the recurrence rate
is high especially in the participants with high risk of recurrence after curative
resection.
Adebelimumab is a humanized anti-PD-L1 monoclonal antibody independently developed by
Hengrui Pharmaceutical. It can specifically bind to PD-L1 molecules to block the
PD-1/PD-L1 pathway that leads to tumor immune tolerance, reactivate the anti-tumor
activity of the immune system, and achieve the goal of treating tumors. As of October 8,
2021, adebelimumab has conducted several clinical studies in various malignant tumor
fields and has shown good anti-tumor efficacy and controllable safety.
Therefore, the investigators plan to conduct a prospective clinical study targeting HCC
participants at high risk of postoperative recurrence, to demonstrate the efficacy and
safety of postoperative adjuvant therapy with adebelimumab combined with apatinib. This
study has the potential to provide efficient new treatment options for participants,
which is of great significance for improving the survival rate and quality of life of
liver cancer participants in general.
A mid-term analysis will be conducted on the recurrence free survival rate and survival
rate, at 6 months after the enrollment of 30 participants.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Participants must meet all of the following conditions in order to be enrolled in this
study:
1. Voluntarily participate in this study and sign an informed consent form.
2. Participants diagnosed with HCC through pathological histology/cytology or
clinically diagnosed with HCC according to the Diagnosis and Treatment Guidelines
for Primary Liver Cancer (2024 Edition).
3. Within 4-12 weeks prior to enrollment, radical resection surgery was performed.
4. Complete recovery from surgical resection within 4 weeks prior to enrollment.
5. High risk factors for postoperative recurrence of hepatocellular carcinoma include
multiple tumors, tumor length>5 cm, poor tumor differentiation (Edmondson III-IV
grade), margin ≤ 1 cm, invasion of Microvasculature or large vessels, lymph node
metastasis, sustained abnormalities in AFP or abnormal prothrombin , etc.
6. Child Pugh liver function rating within 7 days prior to randomization: A or B (≤ 7
points).
7. ECOG PS score within 7 days before randomization: 0-1 points.
8. Have not received systematic anti-tumor treatment for hepatocellular carcinoma in
the past.
9. Expected survival time ≥ 12 weeks.
10. The main organ functions meet the following requirements (within 7 days before
randomization):
(1) Blood routine examination: (excluding hemoglobin, no blood transfusion within 14 days
prior to screening, no use of granulocyte colony-stimulating factor [G-CSF], no
medication correction):
• Neutrophil absolute count ≥ 1.5 × 109/L; Platelets ≥ 75 × 10^9/L; • Hemoglobin ≥ 90
g/L.(Leukocyte and thrombocytopenia caused by splenic hyperfunction can be included in
the group after partial embolization of the splenic artery or medication correction) (2)
Blood biochemistry test (no albumin transfusion within 14 days before screening): Serum
albumin ≥ 28g/L; Total serum bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 3 × ULN; Blood
creatinine ≤ 1.5 x ULN or Cr clearance rate>50ml/min (3) International standardized ratio
(INR) ≤ 2.3 or prothrombin time (PT) exceeding the range of normal control ≤ 6 (4)
Urinary protein<2+(If urinary protein ≥ 2+, 24-hour urine protein quantification is
required, and 24-hour urine protein quantification<1.0g can be included in the group).
11. If suffering from hepatitis B virus (HBV) infection, it is necessary to be willing
to receive antiviral treatment throughout the study period (according to the
diagnostic and treatment guidelines, such as entecavir) and regularly monitor it;
Hepatitis C virus (HCV) ribonucleic acid (RNA) positive subjects must receive
antiviral treatment according to the diagnosis and treatment guidelines, and their
liver function must be within CTCAE1 level elevation.
12.Women with fertility: must agree to contraception from the signing of the informed
consent form until 90 days after the last use of the study drug (whichever is longer).
And the blood HCG test must be negative within 7 days before starting the study
treatment; And it must be non lactation period
Exclusion Criteria:
If a subject meets any of the following conditions, they will not be allowed to enter
this study:
1. Known hepatobiliary carcinoma, sarcoma like hepatocellular carcinoma, combined
hepatocellular-cholangiocarcinoma，and fibrous layer cell carcinoma; Within 5 years
or simultaneously suffering from other active malignant tumors other than
hepatocellular carcinoma (excluding cured skin basal cell carcinoma and cervical
carcinoma in situ).
2. There are uncontrollable extrahepatic metastases, such as lung and brain metastases
(EHS).
3. Previously received local treatment, including therapeutic TACE, transarterial
embolization (TAE), hepatic artery infusion chemotherapy (HAIC), transarterial
radiation embolization (TARE), etc.
4. Participants who are preparing to undergo or have previously received organ or
allogeneic bone marrow transplantation.
5. Participants who are currently accompanied by interstitial pneumonia or interstitial
lung disease, or have a history of interstitial pneumonia or interstitial lung
disease that requires hormone therapy in the past, or other pulmonary fibrosis,
organized pneumonia (such as bronchiolitis obliterans), pneumoconiosis, drug-related
pneumonia, idiopathic pneumonia, or subjects with evidence of active pneumonia or
severe lung function impairment seen on chest computed tomography (CT) images during
screening, are allowed to have radiation induced pneumonia in the radiation field;
Active tuberculosis.
6. Currently, there is active autoimmune disease or a history of autoimmune disease
that may recur (including but not limited to: autoimmune hepatitis, interstitial
pneumonia, uveitis, enteritis, pituitary inflammation, vasculitis, nephritis,
hyperthyroidism, hypothyroidism [subjects that can be controlled only through
hormone replacement therapy can be included]); Subjects with skin diseases that do
not need systematic treatment, such as vitiligo, psoriasis, alopecia, controlled
type I diabetes that receive insulin treatment, or childhood asthma that has
completely alleviated without any intervention after adulthood can be included;
Asthma subjects who require medical intervention with bronchodilators cannot be
included.
7. Suffering from hypertension and unable to achieve good control through
antihypertensive drug treatment (systolic ≥ 140 mmHg or diastolic ≥ 90 mmHg) (based
on the average BP reading obtained from ≥ 2 measurements), it is allowed to achieve
the above parameters through the use of antihypertensive therapy; Previously
experienced hypertensive crisis or hypertensive encephalopathy.
8. Participants with moderate to severe ascites with clinical symptoms who require
therapeutic puncture or drainage, or whose Child Pugh score is greater than 7
(excluding those who only show a small amount of ascites on imaging but do not have
clinical symptoms); Uncontrolled or moderate to equal amounts of pleural effusion
and pericardial effusion.
9. There are clinical symptoms or diseases of the heart that cannot be well controlled,
such as: (1) According to the standards of the New York Heart Association (NYHA),
level II or above cardiac insufficiency or cardiac ultrasound examination: LVEF
(left ventricular ejection fraction)<50%; (2) Unstable angina pectoris; (3) Have
experienced myocardial infarction within one year prior to the start of the research
treatment; (4) Clinically significant supraventricular or ventricular arrhythmias
require treatment or intervention; (5) QTc>480ms (QTc interval is calculated using
the Fridericia formula; if QTc is abnormal, it can be detected continuously three
times every 2 minutes, and the average value is taken).
10. History of spontaneous rupture of liver tumors.
11. Individuals with a history of hepatic encephalopathy.
12. Congenital or acquired immune dysfunction in subjects (such as HIV infected
individuals).
13. There have been incidents of thrombosis or embolism occurring within the first 6
months of treatment, such as cerebrovascular accidents (including transient ischemic
attacks, cerebral hemorrhage, cerebral infarction), pulmonary embolism, etc.
14. Participants with a history of gastrointestinal bleeding or a clear tendency towards
gastrointestinal bleeding within 6 months prior to the start of the study treatment,
such as those at risk of bleeding or severe esophageal and gastric varices, locally
active gastrointestinal ulcer lesions, or continuous positive fecal occult blood,
cannot be included in the study. (If fecal occult blood is positive during the
baseline period, a follow-up examination is required. If the follow-up examination
is still positive, gastroduodenoscopy (EGD) is required. If EGD indicates a risk of
bleeding, esophageal and gastric varices/other gastrointestinal diseases cannot be
included in the study.)
15. Within 6 months prior to the start of treatment, there have been abdominal fistulas,
gastrointestinal perforation, or abdominal abscesses.
16. Severe, unhealed or cracked wounds, as well as active ulcers or untreated fractures.
17. Known genetic or acquired bleeding (such as coagulation dysfunction) or thrombotic
tendencies, such as in hemophilia participants; Currently or recently (within 10
days prior to the start of research treatment), full dose oral or injection
anticoagulants or thrombolytic drugs (prophylactic use of low-dose aspirin, low
molecular weight heparin allowed) have been used for therapeutic purposes.
18. Major vascular diseases (such as aortic aneurysm requiring surgical repair or recent
peripheral arterial thrombosis) occur within 6 months prior to the start of the
study treatment.
19. Severe infection within 4 weeks prior to the start of the study treatment, including
but not limited to hospitalization due to complications of infection, bacteremia, or
severe pneumonia; Oral or intravenous administration of therapeutic antibiotics
within 2 weeks prior to the start of the study treatment (subjects who receive
prophylactic antibiotics, such as preventing urinary tract infections or
exacerbation of chronic obstructive pulmonary disease, are eligible to participate
in the study).
20. It is known that the active ingredients and excipients contained in the
investigational drugs (Adebelimumab, Apatinib) in this study have hypersensitivity
reactions, or have a history of severe allergies to any other monoclonal antibodies
or anti angiogenic targeted drugs.
21. Use immunosuppressive agents or systemic hormone therapy within 14 days prior to the
start of the study to achieve immunosuppressive effects (dose>10mg/day prednisone or
other therapeutic hormones).
22. Received attenuated live vaccine treatment within 28 days prior to the start of the
study treatment, or expected to receive such vaccines during the treatment period
with Adebrelimab or within 60 days after the last dose of Adebrelimab.
23. Received other experimental drug treatments within 28 days or 5 half-lives
(whichever is longer) prior to the start of the study treatment.
24. According to the judgment of the researchers, the subjects may have other factors
that may affect the research results or cause the study to be terminated midway,
such as alcoholism, drug abuse, other serious illnesses (including mental illness)
that require concurrent treatment, serious laboratory test abnormalities, and family
or social factors that may affect the safety of the subjects.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Qilu Hospital of Shandong University
Address:
City:
Jinan
Zip:
250012
Country:
China
Status:
Recruiting
Contact:
Last name:
Tao Li
Phone:
18560085138
Email:
Litao7706@163.com
Contact backup:
Last name:
Dongxu Wang
Phone:
18560084836
Start date:
July 24, 2024
Completion date:
June 2027
Lead sponsor:
Agency:
Qilu Hospital of Shandong University
Agency class:
Other
Source:
Qilu Hospital of Shandong University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06454578
