Trial Title:
HAIC Combined With Durvalumab, Tremelimumab and Bevacizumab as Conversion Therapy for Potentially Resectable Hepatocellular Carcinoma
NCT ID:
NCT05864755
Condition:
Unrescetable Hepatocellular Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Bevacizumab
Durvalumab
Tremelimumab
Conditions: Keywords:
Unrescetable Hepatocellular Carcinoma
Durvalumab
Tremelimumab
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:
HAIC+Durvalumab+Tremelimumab+Bevacizumab
Description:
Tremelimumab：300mg, only once in cycle 1.Durvalumab: 1500mg, iv,q3w Bevacizumab: 15mg/kg,
iv, q3w HAIC: Oxaliplatin plus Fluorouracil/Leucovorin
Arm group label:
HAIC+Durvalumab+Tremelimumab+Bevacizumab
Summary:
To evaluate the efficacy and safety of HAIC combined with Durvalumab, Tremelimumab and
Bevacizumab as first-line therapy in Unresectable hepatocellular carcinoma
Detailed description:
An open label, single-arm, single center, phase II study evaluating HAIC combined with
Durvalumab, Tremelimumab and Bevacizumab as first-line therapy in unresectable
hepatocellular carcinoma
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Provide a written informed consent form (ICF) signed and dated by the patient/legal
representative before conducting any research specific procedures, sampling, and
analysis specified in the protocol.
2. Before collecting genetic analysis samples (optional), provide a signed and dated
written informed consent form for genetic research.
3. At the time of screening, the age should be ≥ 18 years old. For patients under the
age of 20 who are enrolled in China, written informed consent from the patient and
their legal representative should be obtained.
4. Based on the histopathology results of tumor tissue, a patient with stage C
hepatocellular carcinoma complicated with portal vein tumor thrombus BCLC was
diagnosed, with portal vein tumor thrombus type I to III. (Cheng's classification
indicates that the tumor thrombus is mainly located at the level of the liver
segment (secondary branch of the portal vein); Type II refers to the spread of
cancer thrombi invading the left or right branch of the portal vein (primary branch
of the portal vein); Type III refers to cancer thrombus invading the main portal
vein; Type IV refers to tumor thrombus invading superior mesenteric vein or inferior
vena cava.
5. No evidence of extrahepatic diseases was found in baseline chest/abdominal/pelvic
imaging
6. The disease is not suitable for radical surgery, transplantation, or radical
ablation
7. The disease must be suitable for TACE and HAIC treatment, and it is expected that
TACE treatment for local lesions will not exceed 4 times within 16 weeks [DEB-TACE]
8. The Child Pugh grading of liver function is Grade A,the Eastern Oncology
Collaborative Group (ECOG) physical fitness score was 0 or 1
9. Patients with HBV infection [showing positive hepatitis B B virus surface antigen
(HBsAg), and/or positive hepatitis B core antibody (anti HBcAb)] and detectable HBV
DNA (≥ 10IU/mL or higher than the detection limit according to the local
experimental standard) must receive antiviral treatment according to the
institutional diagnosis and treatment routine to ensure adequate virus suppression
(HBV DNA ≤ 2000IU/mL) before enrollment. Patients must maintain antiviral treatment
during the study period and within 6 months after the last administration of the
study drug. For patients who are positive for hepatitis B core antibody (HBc) but
have not detected HBV DNA (<10 IU/ml or below the detection limit of local
laboratory standards), antiviral treatment is not required before enrollment. These
patients need to monitor HBV DNA levels during each course of treatment, and once
HBV DNA is tested (≥ 10 IU/mL or below the detection limit of local laboratory
standards), antiviral treatment begins. Patients who can detect HBV DNA must begin
and maintain antiviral therapy during the study period and within 6 months after the
last administration of the study drug.
10. According to the following mRECIST criteria, at least one measurable intrahepatic
lesion is suitable for repeated evaluation: in intravenous contrast-enhanced CT or
MRI scans, the liver lesion shows typical features of HCC, namely arterial phase
vascular enhancement, venous phase or delayed phase enhancement rapidly disappears
in the non necrotic part at baseline (arterial phase IV contrast agent enhancement),
and its longest diameter can be accurately measured to be ≥ 10 mm
11. The definition of good organ and bone marrow function is as follows. Within 14 days
before the start of the first dose, standards "a", "b", "c", and "f" cannot be met
through blood transfusion, infusion, or receiving supportive therapies such as
growth factors
1. Hemoglobin ≥ 9.0 g/dL
2. Absolute neutrophil count ≥ 1000/µ L
3. Platelet count ≥ 75000/ μ L
4. Total bilirubin ≤ 2.0 × Upper limit of normal value (ULN)
5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 × ULN
6. Albumin ≥ 2.8 g/dL
7. International normalized ratio (INR) ≤ 1.6
8. 2+or lower urine test strip reading
9. Calculate creatinine clearance rate (CL) ≥ 30mL/min, and measure male
creatinine CL=weight (kg) using Cockcroft Fault (using actual body weight) or
24-hour urine creatinine CL × (140 Age) (mL/min) 72 × Serum creatinine (mg/dL)
Female: creatinine CL=weight (kg) × (140- Age) × 0.85（mL/min）72 × Serum
creatinine (mg/dL)
12. Must have an expected lifespan of at least 12 weeks
13. Weight>30 kg
14. No gender limit
Exclusion Criteria:
1. History of kidney disease or nephrotic syndrome
2. Cardiovascular diseases with clinical significance
3. Major traumatic injury occurred within the first 4 weeks of randomization
4. Known genetic factors for bleeding or thrombosis; Any previous or current evidence
indicating a tendency to bleed
5. Systematic anticoagulant therapy is allowed, except for vitamin K antagonists
6. History of arterial embolism events, including stroke or myocardial infarction
7. Patients with unhealed wounds, active ulcers, or fractures. For granulation wounds
in the second stage of healing, as long as there is no evidence of surface cracking
or infection in patients, they meet the inclusion criteria but require wound
examination every 3 weeks
8. Abdominal wall fistula or gastrointestinal perforation, refractory unhealed gastric
ulcer, or active gastrointestinal bleeding within 6 months before enrollment
9. Patients who have undergone any surgery within the past 28 days (diagnostic biopsy
is acceptable)
10. Uncontrolled hypertension is defined as systolic blood pressure>150 mmHg or
diastolic blood pressure>90 mmHg, with or without taking antihypertensive drugs.
Patients who experience an increase in blood pressure (BP) for the first time can be
enrolled if using or adjusting antihypertensive drugs can lower their blood pressure
to the inclusion criteria.
11. Diagnosed fibrolaminar HCC, sarcomatous HCC, or mixed cholangiocarcinoma and HCC
12. Have a history of hepatic encephalopathy within the past 12 months, or require
medication to prevent or control encephalopathy (such as using lactulose, rifaximin,
etc. for hepatic encephalopathy).
13. Large portal vein thrombosis was seen in the baseline/qualification test imaging,
and patients with type IV procedures were excluded
14. Patients with infiltrative HCC
15. Have a history of homologous organ transplantation
16. Active or previously recorded autoimmune diseases or inflammatory diseases
(including inflammatory bowel disease [such as colitis or Krohn's disease],
diverticulitis [except diverticulosis], systemic lupus erythematosus, sarcoidosis
syndrome or Wegener's syndrome [such as granulomatous vasculitis, Gray's disease,
rheumatoid arthritis, hypophysitis and uveitis]). There are the following exceptions
to this standard:
- Patients with vitiligo or hair loss
- Patients with stable hypothyroidism after receiving hormone replacement therapy
(such as after Hashimoto's thyroiditis) Any chronic skin disease patient who
does not require systemic treatment
- Patients with no active diseases within the past 5 years can be included, but
only after consulting the research doctor can they be included Patients with
celiac disease who can be controlled solely by diet
17. Uncontrolled complications, including but not limited to: persistent or active
infection (except for the above HBV or HCV), symptomatic congestive heart failure,
uncontrollable diabetes, uncontrollable hypertension, unstable angina pectoris,
uncontrollable arrhythmia, active ILD, severe chronic GI disease with diarrhea, or
suffering from a condition that may limit compliance with the study requirements
Mental illness/social issue conditions that significantly increase the risk of AE or
affect the subject's ability to provide written informed consent.
18. History of other primary malignant tumors, except for the following situations
Malignant tumors that have been treated for the purpose of cure, and have no known
active diseases for ≥ 5 years before the first administration of IP, with a low
potential risk of recurrence
- Fully treated non melanoma skin cancer or malignant lentiginous nevus without
disease evidence Fully treated in situ cancer with no evidence of disease
19. History of meningeal cancer
20. History of active primary immunodeficiency
21. Active infection, including tuberculosis (clinical evaluation, including clinical
history, physical examination and imaging examination results, as well as
tuberculosis testing according to local clinical standards) or human
immunodeficiency virus (HIV 1/2 antibody positive)
22. Patients who are co infected with HBV and HCV, or co infected with HBV and hepatitis
D virus (HDV). (HBV infection refers to the presence of HBsAg and/or anti HBcAb, and
detectable HBV DNA ≥ 10 IU/mL or according to local laboratory standards detection
limit; HCV positive infection refers to detectable HCV RNA; HDV positive infection
refers to the presence of anti HDV antibodies.)
23. Except for hair loss, vitiligo, and laboratory values specified in the inclusion
criteria, any unrelieved NCI (National Cancer Institute) CTCAE v5.0 ≥ Level 2 events
caused by previous anti-cancer treatment
24. Known to cause allergic or hypersensitive reactions to any investigational drug or
any of its excipients
25. Have a history of allogeneic bone marrow transplantation and active chronic graft
versus host disease
26. Have received anti PD-1, anti PD-L1, or anti CTLA-4 treatment before the first
administration of IP
27. Previously received TACE (transcatheter arterial chemoembolization), TAE
(transcatheter arterial embolization), or TARE (transcatheter arterial
radioembolization)
28. Previously received systemic anti-cancer treatment for HCC
29. IP has been vaccinated with attenuated live vaccine within 30 days before the first
administration. Note: If enrolled, patients are not allowed to receive attenuated
live vaccines during IP treatment and within 30 days after the last administration
of IP.
30. Currently in use or using immunosuppressive drugs within 14 days before the first
dose of IP administration. This standard has the following exceptions:
- Intranasal, inhalation, topical steroids, or local injection of steroids (such
as intra-articular injection) Whole body corticosteroid therapy with no more
than 10 mg/day prednisone or its equivalent physiological dose as a preventive
use of steroid hormones for hypersensitivity reactions (such as CT scan
pre-treatment medication)
31. Previously received IP allocation in this study
32. Simultaneously enroll in another clinical study, unless the study is an
observational (non intervention) clinical study or during the follow-up period of an
intervention study
33. Prior to randomization or treatment, participants had previously participated in
clinical studies of immune checkpoint inhibitors, regardless of treatment group
allocation.
34. From screening to 6 months after the last administration of IP, pregnant or
lactating female patients, or male or female patients with fertility, are unwilling
to use efficient contraceptive measures. According to the patient's preferred and
habitual lifestyle, abstinence during treatment and abstinence is an acceptable
contraceptive measure.
35. Patients who, in the judgment of the researcher, are unlikely to comply with the
research steps, limitations, and requirements shall not participate in this study.
Gender:
All
Minimum age:
18 Years
Maximum age:
85 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Tianjin Cancer Hospital Airport Hospital
Address:
City:
Tianjin
Zip:
300308
Country:
China
Status:
Recruiting
Contact:
Last name:
Huikai Li, MD
Phone:
18622228639
Email:
tjchlhk@126.com
Contact backup:
Last name:
Yang Liu, MD
Phone:
17694950696
Start date:
June 20, 2023
Completion date:
December 2025
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/NCT05864755
