Trial Title:
HAIC Combined With Adebrelimab Plus Apatinib as the First-line Treatment for HCC in BCLC Stage C: An Open-label, Single-arm, Phase II Study
NCT ID:
NCT06482008
Condition:
Hepatocellular Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Apatinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Hepatic arterial infusion chemotherapy(HAIC) combined with adebrelimab plus apatinib
Description:
HAIC every 3 weeks until 6 treatments have been completed, or HAIC therapy is terminated
if patients have not reached 6 treatments and experience intolerable adverse effects;
adebrelimab, fixed dose 1200 mg, IV, D1, every 21 days (Q3W), in combination with
apatinib, 250 mg (0.25 g), orally, once daily (QD), consecutively dosing in 3-week
(21-day) treatment cycles. Study treatment will continue until the subject develops an
intolerable toxic reaction, withdraws informed consent, and progresses according to
RECIST v1.1 as confirmed by the investigator (after the subject develops disease
progression as defined by RECIST v1.1, if the investigator assesses that the subject is
still clinically beneficial and can tolerate the study treatment, the subject may
continue to receive the study drug; if it is considered that the subject no longer has
clinical benefit, then treatment may be terminated), or other termination criteria
specified in the protocol, whichever occurs first.
Arm group label:
HAIC+adebrelimab+apatinib
Summary:
This is an open, single-arm clinical study to observe and evaluate the efficacy and
safety of first-line treatment of patients with stage C hepatocellular carcinoma of BCLC
at HAIC in combination with adebrelimab and apatinib.
Patients with stage C hepatocellular carcinoma of BCLC who have not received prior
systemic therapy and cannot be resected will be selected for the study. The study has
objective response rate (ORR) as the primary study endpoint and is planned to enroll 33
subjects. Patients eligible for enrollment will receive HAIC in combination with
adebrelimab and apatinib.
Subjects will receive study treatment after being fully informed and signing an informed
consent form and being screened for eligibility.HAIC treatment (FOLFOX regimen) will be
administered every 3 weeks until 6 treatments have been completed or HAIC treatment is
terminated if the patient experiences intolerable adverse effects before 6 treatments
have been achieved; adebrelimab, fixed dose 1200 mg, IV, D1, every 21 days (Q3W), in
combination with Apatinib, 250 mg (0.25 g), orally, once daily (QD), administered
consecutively in 3-week (21-day) treatment cycles. Study treatment will continue until
the subject develops an intolerable toxic reaction, withdraws informed consent, and
progresses in accordance with RECIST v1.1 disease progression as identified by the
investigator (after the subject has progressed in accordance with the definition of
RECIST v1.1, the subject may continue to receive study drug if the investigator assesses
that the subject is still clinically beneficial and can tolerate the study treatment, or,
if it is deemed that the subject no longer has clinical benefit, then treatment may be
terminated), or other termination criteria specified in the protocol, whichever occurs
first.
Subjects will all have a safety visit at D1 of each treatment cycle after enrollment in
the study, and will continue to have a safety visit and survival follow-up after
completion of treatment.
Tumor imaging assessment will be performed every 6 weeks after enrollment to assess
efficacy. Additional imaging examinations and assessments may be performed at any time
during the study if clinically indicated. Tumor imaging assessment will continue until
there is disease progression confirmed by the investigator according to RECIST v1.1
criteria or termination of treatment, whichever occurs later. For subjects who end
treatment for reasons other than investigator-confirmed disease progression (according to
RECIST v1.1), regular follow-up tumor imaging assessments will also continue after the
end of treatment.
If the subject withdraws consent, has started other anti-tumour therapy (other than PCPs)
or dies prior to the occurrence of investigator-confirmed disease progression according
to RECIST v1.1 criteria or termination of treatment, no further imaging assessment will
be required. If the subject does not meet the above termination criteria for imaging
assessment, the assessment of tumour efficacy for all three efficacy assessment criteria
(RECIST v1.1, mRECIST, imRECIST) will need to be continued even if there is disease
progression for one of the efficacy assessment criteria.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients voluntarily enrolled in the study and signed an informed consent form;
2. ≥18 years of age (counted on the date of signing informed consent), both male and
female;
3. Patients with hepatocellular carcinoma diagnosed by EASL/AASLD diagnostic criteria,
pathohistological or cytological confirmation;
4. Subjects must be able to provide fresh or archived tumour tissue (formalin-fixed,
paraffin-embedded [FFPE] tissue blocks or at least 5 unstained FFPE slides) and
their pathology report. If the subject can provide less than 5 unstained slides or
if tumour tissue is not available (e.g., exhausted because of previous diagnostic
testing), enrolment may be allowed on a case-by-case basis after discussion;
5. Barcelona Clinical Liver Cancer Staging (BCLC, see Annex 1) stage C and not suitable
for surgery or progressed after surgery and/or local treatment;
6. Patients who have progressed after local therapy, where local therapy (including but
not limited to surgery, radiotherapy, hepatic artery embolisation, TACE, hepatic
artery perfusion, radiofrequency ablation, cryoablation, or percutaneous ethanol
injection) has been completed at least 4 weeks prior to the baseline imaging scan
and where toxic reactions (other than alopecia) due to local therapy must have
recovered to the National Cancer Institute-Common Terminology Criteria for Adverse
Events version 5.0 ( NCI-CTCAE v5.0) rating ≤ Grade 1;
7. not have received any prior systemic therapy for HCC
8. At least one measurable lesion (spiral CT scan length ≥ 10 mm or short diameter of
enlarged lymph node ≥ 15 mm according to RECIST v1.1; lesions previously treated
with localised therapy can be used as target lesions after definitive progression
according to RECIST v1.1).
9. Child-Pugh Liver Function Class (see Annex 2): Grade A or B.
10. Eastern Cooperative Oncology Group (ECOG) physical status score of 0 to 2 (see Annex
3 for ECOG scoring criteria);
11. Expected survival ≥ 12 weeks;
12. Major organ function is basically normal
13. If the patient has active hepatitis B virus (HBV) infection and is willing to
receive antiviral therapy (based on the local standard of care, e.g., entecavir) for
the entire duration of the study, enrolment will be determined on an individual
basis by the physician, with monitoring of viral copy number; Hepatitis C virus
(HCV) ribonucleic acid (RNA)-positive patients must be receiving antiviral therapy
according to standard local treatment guidelines and have liver function within
CTCAE grade 1 elevation;
14. Females of childbearing potential: must agree to abstain (avoid heterosexual
intercourse) or use a reliable, effective method of contraception for at least 120
days from the time of signing the Informed Consent Form until after the last dose of
study drug. Must have a negative serum HCG test within 7 days prior to starting
study treatment; and must not be breastfeeding. A female patient is considered
fertile if she is menstruating, has not yet reached postmenopausal status (≥12
consecutive months without menstruation, with no reason other than menopause
identified), and has not undergone a sterilisation procedure (e.g., hysterectomy,
bilateral tubal ligation, or bilateral salpingo-oophorectomy).
15. For male patients whose partner is a woman of childbearing potential, they must
agree to abstain from sex or use a reliable, effective method of contraception for
at least 120 days from the time of signing the informed consent form until the last
dose of study drug. Male subjects must also agree not to donate sperm during the
same time period. Male subjects whose partners are pregnant are required to use
condoms and no other method of contraception.
Exclusion Criteria:
1. Known hepatobiliary cell carcinoma, sarcomatoid HCC, mixed cell carcinoma and
fibroblastic laminar cell carcinoma; and other active malignant tumours other than
HCC within 5 years or concurrently. Cured limited tumours such as basal cell
carcinoma of the skin, squamous carcinoma of the skin, superficial bladder
carcinoma, carcinoma in situ of the prostate, carcinoma in situ of the cervix, and
carcinoma in situ of the breast may be enrolled;
2. Patients who are preparing for or have previously undergone organ or allogeneic bone
marrow transplantation;
3. Have received other experimental drug therapy within 28 days prior to initiation of
study treatment;
4. Those with clinically symptomatic moderate or severe ascites i.e. requiring
therapeutic puncture or drainage or Child-Pugh score >2 (except for those with only
a small amount of ascites on imaging but without clinical symptoms); uncontrolled or
moderate or greater pleural effusion, pericardial effusion;
5. History of gastrointestinal bleeding or a definite propensity for gastrointestinal
bleeding within 6 months prior to the start of study treatment;
6. Abdominal fistula, gastrointestinal perforation or abdominal abscess within 6 months
prior to start of study treatment;
7. Known hereditary or acquired bleeding (e.g., coagulation disorders) or thrombotic
tendencies, such as in patients with haemophilia; current or recent (within 10 days
prior to start of study treatment) use of full-dose oral or injectable anticoagulant
or thrombolytic medications for therapeutic purposes (prophylactic use of low-dose
aspirin, low molecule heparin is permitted);
8. Have had a thrombotic or embolic event, such as cerebrovascular accident (including
transient ischaemic attack, cerebral haemorrhage, cerebral infarction), pulmonary
embolism, etc., within 6 months prior to the start of study treatment;
9. Have a clinical cardiac condition or disease that is not well controlled, such
as:(1) Class II or higher cardiac insufficiency according to the New York Heart
Association (NYHA) criteria;(2) Unstable angina pectoris;(3) Myocardial infarction
within 1 year prior to the start of study treatment;(4) clinically significant
supraventricular or ventricular arrhythmia requiring treatment or intervention;
10. Hypertension that is not well controlled by antihypertensive medication, allowing
the above parameters to be achieved through the use of antihypertensive therapy;
previous hypertensive crisis or hypertensive encephalopathy;
11. Major vascular disease (e.g., aortic aneurysm requiring surgical repair or recent
peripheral arterial thrombosis) within 6 months prior to the start of study
treatment; severe, unhealed or gaping wounds as well as active ulcers or untreated
bone fractures; major surgical procedure (other than diagnostic) within 4 weeks
prior to the start of study treatment or anticipation of the need for major surgical
procedure during the study period;
12. inability to swallow tablets, malabsorption syndrome, or any condition that
interferes with gastrointestinal absorption; history of intestinal obstruction
and/or history of clinical signs or symptoms of gastrointestinal obstruction,
including incomplete obstruction related to pre-existing conditions or requiring
routine parenteral hydration, parenteral nutrition, or tube feedings, within 6
months prior to the initiation of study treatment: at the time of the initial
diagnosis if there is an incomplete obstruction/obstruction syndrome/intestinal
obstruction sign/symptom Patients may be eligible for enrolment in the study if they
receive definitive (surgical) treatment to abate symptoms;
13. Evidence of intra-abdominal pneumoperitoneum that cannot be explained by puncture or
recent surgical intervention;
14. previous or current central nervous system metastases; metastatic disease involving
major airways or blood vessels (e.g. complete occlusion of the portal trunk or vena
cava due to tumour 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 centrally located, large mediastinal tumour masses (<30 mm
from the crural crest);
15. Persons with a history of hepatic encephalopathy; 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 judgement and management of immune-related
pulmonary toxicity such as pulmonary fibrosis, mechanised pneumonitis (e.g.,
occlusive bronchiectasis), pneumoconiosis, drug-associated pneumonitis, idiopathic
pneumonitis, or in the case of screening chest computed tomography (CT) scans
Subjects with evidence of active pneumonia visible on the chart or severely impaired
lung function, permitted to have had radiation pneumonitis in the radiation field;
active tuberculosis;
16. Presence of active autoimmune disease or history of autoimmune disease with
potential for relapse (including, but not limited to: autoimmune hepatitis,
interstitial pneumonitis, uveitis, enteritis, pituitary gland inflammation,
vasculitis, nephritis, hyperthyroidism, hypothyroidism [subjects who can be
controlled by hormone replacement therapy only may be included]); Subjects who
suffer from a skin condition that does not require systemic treatment such as
vitiligo, psoriasis, 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;
17. Use of 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);
18. Use of strong CYP3A4/ CYP2C19 inducers including rifampicin (and its analogues) and
guanfacine or strong CYP3A4/ CYP2C19 inhibitors within 14 days prior to initiation
of study treatment;
19. Known history of severe allergy to any monoclonal antibody, anti-angiogenesis
targeted drug;
20. Severe infection within 4 weeks prior to initiation of study treatment, including,
but not limited to, hospitalisation for complications of infection, bacteraemia 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);
21. Patients with congenital or acquired immune deficiency (e.g., HIV-infected);
22. Co-infection with Hepatitis B and Hepatitis C;
23. Prior treatment with other anti-PD-1 antibodies or other immunotherapies targeting
PD-1/PD-L1, or prior treatment with apatinib;
24. has received a live attenuated vaccine within 28 days prior to initiation of study
treatment or anticipates the need for such vaccine during adebenosumab treatment or
within 60 days of the last dose of adebenosumab
25. in the judgement of the investigator, the patient has other factors that may affect
the results of the study or cause this study to be forcibly terminated midway
through, such as alcoholism, drug abuse, other serious illnesses (including
psychiatric illnesses) that require comorbid treatment, serious laboratory test
abnormalities, concomitant family or social factors, which would affect the
patient's safety.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
June 19, 2024
Completion date:
February 1, 2026
Lead sponsor:
Agency:
Sun Yat-sen University
Agency class:
Other
Source:
Sun Yat-sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06482008
