Trial Title:
Evaluation of Effectiveness and Safety of HAIC in Combination With Adebrelimab and Bevacizumab for Potentially Resectable Hepatocellular Carcinoma
NCT ID:
NCT06405061
Condition:
Adebrelimab
Hepatocellular Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Bevacizumab
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
Description:
Adebrelimab: 1200 mg, IV, q3w
Arm group label:
Study arm
Other name:
Bevacizumab
Other name:
HAIC
Summary:
Primary liver cancer mainly consists of three different pathologic types: hepatocellular
carcinoma, intrahepatic cholangiocarcinoma, and hybrid HCC-ICC, of which HCC accounts for
90%. According to GLOBOCAN 2018 data, liver cancer is the sixth most prevalent tumor in
the world, with about 841,100 new liver cancer cases and 781,600 deaths per year
globally, which is the second leading cause of tumor deaths in men worldwide. China is a
high incidence area of liver cancer, accounting for about 50% of the global incidence and
deaths.
The treatment of HCC varies according to disease stage, which is based on the BCLC
classification system, Child-Pugh liver function rating, and extent of disease.
Approximately 30% of HCC cases are diagnosed in the early stages (i.e., BCLC stage 0 or
A), and the main treatment options include surgical resection, ablation techniques, and
liver transplantation. However, the 5-year recurrence rate remains as high as 70%. The
recommended treatment for intermediate stage HCC (i.e., BCLC stage B) is hepatic artery
intervention, i.e., transarterial chemoembolization (TACE), but the scope of
applicability is limited due to concomitant disease and liver impairment factors, some
patients do not derive a survival benefit from it, and patients ultimately progress after
treatment and are no longer suitable for further TACE.
In recent years, the multi-drug combination therapy of systemic drugs combined with local
therapy has also been gradually adopted, and studies have reported the feasibility of
target drugs combined with ICI, TACE or HAIC for the treatment of unresectable
hepatocellular carcinoma. The therapeutic aim of Adebrelimab (SHR-1316) is to inhibit
tumor growth by specifically blocking the binding of PD-1 to PD-L1 and terminating the
immunosuppressive signals generated by this receptor on T cells, so that T cells can
re-recognize tumor cells and produce killing effects on them.
This study proposes an evaluation to explore the efficacy and safety of irinotecan
liposome-based hepatic arterial perfusion chemotherapy (FOLFIRI) in combination with
adebrelimab and bevacizumab for the treatment of potentially resectable hepatocellular
carcinoma.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. patients voluntarily enrolled in the study and signed an informed consent form.
2. 18-75 years old, both male and female.
3. patients with HCC diagnosed histologically, cytologically, or clinically.
4. CNLC-IIb to IIIaHCC (IIIa is limited to combined portal vein branch thrombosis
Ching's staging grade I/II) of the Guidelines for the Management of Primary Liver
Cancer (2022 edition).
5. not have received any prior local and systemic therapy for HCC.
6. at least one measurable lesion (the measurable lesion is ≥10 mm in long diameter or
≥15 mm in short diameter of enlarged lymph node on spiral CT scan according to
RECISTv1.1).
7. Child-Pugh score ≤7.
8. ECOG score:0~1.
9. Expected survival ≥12 weeks.
10. Vital organs function in accordance with the following requirements (within 7 days
prior to initiation of study treatment).
(1) Routine blood tests: (except hemoglobin, which has not been transfused, granulocyte
colony-stimulating factor [G-CSF], or corrected with medication within 14 days prior to
screening): absolute neutrophil count ≥ 1.5 x 109/L; platelets ≥ 75 x 109/L; hemoglobin ≥
90 g/L.
(2) Biochemical tests: (no albumin transfusion within 14 days prior to screening): serum
albumin ≥29g/L; serum total bilirubin ≤1.5×upper limit of normal range (ULN); alanine
aminotransferase (ALT), aspartate aminotransferase acid enzyme (AKP) ≤5×ULN; serum
creatinine (Cr) ≤1.5ULN or Cr clearance >50mL/min.
(3) International normalized ratio (INR) ≤ 2.3 or prothrombin time (PT) exceeding the
range of normal control ≤ 6 seconds.
(4) Urine protein <2+ (if urine protein ≥2+, 24-hour (h) urine protein quantification can
be performed, and 24-h urine protein quantification <1.0 g can be enrolled).
11. If the patient has active hepatitis B virus (HBV) infection: HBV-deoxyribonucleic
acid (DNA) must be <500 IU/mL (or <2500 copies/mL if only copies/mL are available at
the study center), and has received at least 14 days of anti-HBV treatment prior to
the initiation of study treatment (based on the standard of care in the local area,
e.g., entecavir) and is willing to be enrolled at the time of study treatment.
Patients who are hepatitis C virus (HCV) ribonucleic acid (RNA)-positive must be
receiving antiviral therapy according to standard local treatment guidelines and
have liver function within CTCAE grade 1 elevation.
12. Patients must agree to use contraception for at least 120 days from the date of
informed consent until the last dose of study drug. Must have had a negative serum
HCG test within 7 days prior to starting study treatment; must not be breastfeeding.
Exclusion Criteria:
1. Known hepatobiliary ductal cell carcinoma, sarcomatoid HCC, mixed cell carcinoma and
fibrous platysmal cell carcinoma; active malignant tumors other than HCC within 5
years or at the same time. Cured limited tumors, such as basal cell carcinoma of the
skin, squamous carcinoma of the skin, superficial bladder cancer, carcinoma in situ
of the prostate, carcinoma in situ of the cervix, carcinoma in situ of the breast,
etc. can be enrolled.
2. Patients with combined portal vein branch thrombosis of grade III or above in
Cheng's staging.
3. Patients who are going to undergo or have previously undergone organ or allogeneic
bone marrow transplantation.
4. Patients with clinically symptomatic moderate or severe ascites that requires
therapeutic puncture or drainage or Child-Pugh score >2 (except those with only a
small amount of ascites on imaging but not accompanied by clinical symptoms);
uncontrolled or moderate amount or more of pleural effusion or pericardial effusion.
5. Esophageal varices or fundal bleeding due to portal hypertension within the past 6
months; Presence of severe (G3) varices detected by endoscopy 3 months prior to
initial dosing; Evidence of portal hypertension (including imaging findings of
spleen more than 10 cm in length and platelets less than 100) and high risk of
bleeding as assessed by the investigator.
6. Arteriovenous thromboembolic events within the past 6 months, including myocardial
infarction, unstable angina, cerebrovascular accident or transient ischemic attack,
pulmonary embolism, deep vein thrombosis, or any other history of severe
thromboembolism. Implantable IV port or catheter derived thrombosis, or superficial
vein thrombosis, except for thrombus stabilization after routine anticoagulation
therapy.
7. Known hereditary or acquired bleeding (e.g., coagulation disorders) or thrombotic
tendencies, such as in patients with hemophilia; Currently using or have recently
(within 10 days prior to initiation of study treatment) used for therapeutic
purposes full-dose oral or injectable anticoagulant or thrombolytic medications
(prophylactic use of low-dose aspirin, low molecule heparin is permitted).
8. current or recent (within 10 days prior to start of study treatment) treatment with
aspirin (>325 mg/day (maximum antiplatelet dose) or dipyridamole, ticlopidine,
clopidogrel and cilostazol.
9. Thrombotic or embolic events, such as cerebrovascular accidents (including transient
ischemic attack, cerebral hemorrhage, cerebral infarction), pulmonary embolism,
etc., within 6 months prior to the start of study treatment.
10. Uncontrolled cardiac clinical symptoms or diseases, such as: (1) Class II or higher
cardiac insufficiency according to the New York Heart Association (NYHA) criteria
(see Annex 5) or cardiac ultrasound: LVEF (left ventricular ejection fraction) <
50%; (2) unstable angina pectoris; (3) myocardial infarction within 1 year prior to
the start of the study; (4) clinically significant supraventricular or ventricular
arrhythmia requiring a cardiovascular or cardioembolic intervention; and (5)
clinically significant supraventricular or ventricular arrhythmia requiring a
cardiovascular or cardiac intervention; (6) cardiac disease or disease of the heart.
or ventricular arrhythmia requiring treatment or intervention; (5) QTc>450ms (men);
QTc>470ms (women) (QTc intervals were calculated using the Fridericia formula; if
the QTc was abnormal, three consecutive tests were performed at 2-minute intervals,
and the average value was taken).
11. have hypertension that is not well controlled by antihypertensive medication
(systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg) (based on the average of ≥2 BP
readings), allowing the achievement of the above parameters through the use of
antihypertensive therapy; have had a previous hypertensive crisis or hypertensive
encephalopathy.
12. significant vascular disease (e.g., aortic aneurysm requiring surgical repair or
recent peripheral arterial thrombosis) within 6 months prior to the start of study
treatment; and
13. severe, unhealed or gaping wounds and active ulcers or untreated fractures.
14. major surgical treatment (other than diagnostic) within 4 weeks prior to the start
of study treatment or anticipated need for major surgical treatment during the study
period.
15. previous intestinal obstruction and/or previous clinical signs or symptoms of
gastrointestinal obstruction within 6 months prior to initiation of study treatment,
including incomplete obstruction related to a pre-existing condition or requiring
routine parenteral hydration, parenteral nutrition, or tube feeding/tube feeding.
16. Patients may be enrolled in the study if at the time of initial diagnosis patients
with incomplete obstruction/obstruction syndrome/signs/symptoms of intestinal
obstruction receive definitive (surgical) treatment to abate symptoms.
17. evidence of an intra-abdominal pneumoperitoneum that cannot be explained by puncture
or recent surgery.
18. previous or current central nervous system metastases.
19. Metastatic disease involving major airways or blood vessels (e.g., complete
occlusion of the portal trunk or vena cava due to tumor invasion, which refers to
the confluence of the splenic vein and the superior mesenteric vein, and the
division of the hepatic portal vein into right and left branches) or a centrally
located large mediastinal tumor mass (<30 mm from the crista longitudinalis).
20. those with a history of hepatic encephalopathy.
21. current concomitant interstitial pneumonia or interstitial lung disease, or a
previous history of interstitial pneumonia or interstitial lung disease requiring
hormonal therapy, or other conditions that may interfere with the determination and
management of immune-related pulmonary toxicity such as pulmonary fibrosis, organic
pneumonia (e.g., occlusive bronchiectasis), pneumoconiosis, drug-associated
pneumonia, idiopathic pneumonia, or active pneumonia as seen on a screening chest
computed tomography (CT) picture Evidence or severely impaired lung function in
subjects with a history of radiation pneumonitis in the permitted radiation field;
active tuberculosis.
22. presence of active autoimmune disease or history of autoimmune disease with
potential for relapse (including, but not limited to: autoimmune hepatitis,
interstitial pneumonitis, uveitis, enterocolitis, pituitary gland inflammation,
vasculitis, nephritis, hyperthyroidism, hypothyroidism [subjects who can be
controlled by hormone replacement therapy only are eligible for enrollment]);
subjects with skin conditions that do not require systemic treatment such as
vitiligopsoriasis, alopecia areata, controlled type I diabetes mellitus treated with
insulin or asthma that has completely resolved in childhood and does not require any
intervention in adulthood may be included; asthmatics requiring medical intervention
with bronchodilators may not be included.
23. Immunosuppressive or systemic hormone therapy for immunosuppression within 14 days
prior to initiation of study treatment (dose >10 mg/day prednisone or other
equipotent hormone).
24. Use of strong CYP3A4/CYP2C19 inducers including rifampicin (and its analogs) and
oncolytic or strong CYP3A4/CYP2C19 inhibitors within 14 days prior to initiation of
study treatment.
25. severe infection within 4 weeks prior to initiation of study treatment, including
but not limited to hospitalization for complications of infection, bacteremia, or
severe pneumonia; therapeutic antibiotics given orally or intravenously within 2
weeks prior to initiation of study treatment (patients receiving prophylactic
antibiotics (e.g., for prevention of urinary tract infection or exacerbation of COPD
are eligible for study participation).
26. Patients with congenital or acquired immune deficiency (e.g., HIV-infected
patients).
27. Combined hepatitis B and hepatitis C co-infection.
28. Use of immunosuppressive drugs within 4 weeks prior to the first dose; and
29. Received live attenuated vaccine within 4 weeks prior to the first dose or plan to
receive live attenuated vaccine during the study.
30. Received a traditional Chinese medicine with an antitumor indication or a drug with
immunomodulatory effects within 2 weeks prior to the first dose of study drug.
31. previous treatment with other anti-PD-1 antibodies or other immunotherapy targeting
PD-1/PD-L1.
32. palliative radiotherapy to non-target lesions for symptom control is permitted and
must have been completed at least 2 weeks prior to the initiation of study treatment
use, with no recovery from radiotherapy-induced adverse events to ≤ CTCAE grade 1.
33. have received other experimental drug therapy within 28 days prior to initiation of
study treatment.
34. In the judgment of the investigator, the patient has other factors that may affect
the results of the study or cause this study to be forced to be terminated in
midstream, such as alcoholism, drug abuse, other serious illnesses (including
psychiatric illnesses) that require comorbid treatment, serious laboratory test
abnormalities, accompanied by family or social factors that would affect the
patient's safety.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Peking Union Medical College Hospital
Address:
City:
Beijing
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Haitao Zhao, MD
Phone:
13901246374
Facility:
Name:
Tianjin Cancer Hospital Airport Hospital
Address:
City:
Tianjin
Zip:
300308
Country:
China
Status:
Recruiting
Contact:
Last name:
Huikai Li, Doctor
Phone:
18622228639
Email:
tjchlhk@126.com
Contact backup:
Last name:
Yang Liu, MD
Phone:
17694950696
Email:
tjchlhk@126.com
Facility:
Name:
Third Central Hospital of Tianjin
Address:
City:
Tianjin
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Cheng Lou, MD
Phone:
1552224 2700
Facility:
Name:
Tianjin First Central Hospital
Address:
City:
Tianjin
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Zilin Cui, MD
Phone:
13602184643
Start date:
May 1, 2024
Completion date:
August 1, 2027
Lead sponsor:
Agency:
Tianjin Medical University Cancer Institute and Hospital
Agency class:
Other
Source:
Tianjin Medical University Cancer Institute and Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06405061
