Trial Title:
Perioperative Risk of Immunotherapy Based Neoadjuvant and Conversion Therapy for Hepatocellular Carcinoma
NCT ID:
NCT06571396
Condition:
Carcinoma, Hepatocellular
Immunotherapy
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Study type:
Observational
Overall status:
Recruiting
Study design:
Time perspective:
Retrospective
Summary:
This study aims to retrospectively collect a cohort of participants with hepatocellular
carcinoma who received immunotherapy-based neoadjuvant/translational treatment. A
multi-dimensional and multi-method analysis plan will be adopted. The goal is to provide
solutions for better application of neoadjuvant immunotherapy and to offer better
evidence for conducting prospective clinical research on hepatocellular carcinoma.
Detailed description:
Hepatocellular carcinoma (HCC) is indeed a significant health concern, especially in
regions like China where its incidence and mortality rates are notably high. Radical
resection is the main method for curing HCC. However, about 64% of HCC participants are
diagnosed at mid to late stages, making surgical resection unsuitable as the first
choice. Additionally, the short-term recurrence rate after HCC surgery is relatively
high, with a five-year recurrence and metastasis rate reaching 70%. Therefore, increasing
the radical resection rate and reducing the postoperative recurrence rate are key
measures to improve prognosis.
With the development of tumor genomics and immunology, systematic treatment based on
immune checkpoint inhibitors (ICIs) has shown remarkable efficacy in improving HCC
prognosis. The application of ICIs in perioperative treatment of solid tumors can
effectively reduce tumor burden while expanding the immune effect of tumor antigens,
thereby increasing resection rates and reducing recurrence rates.
Currently, neoadjuvant immunotherapy has achieved good treatment outcomes in lung cancer,
esophageal cancer, and gastric cancer. However, the increased antitumor treatment may
lead to potential treatment side effects. For neoadjuvant immunotherapy in solid tumors,
preoperative treatment can pose perioperative risks such as tissue edema, adhesions, and
excessive bleeding during surgery. Due to the hidden effects of some immune therapy
adverse reactions, these perioperative risks require particular attention and research.
Neoadjuvant immunotherapy for HCC is still in its infancy, with a limited number of cases
reported by various centers, and there are currently no large-sample clinical studies
available.
The investigators intend to establish a cohort of HCC participants undergoing
neoadjuvant/conversion treatment. It will employ a multidimensional and multi-method
analysis plan to systematically investigate the perioperative risks associated with
immunotherapy in these participants, aiming to provide solutions for better application
of neoadjuvant immunotherapy in HCC, while also offering improved evidence for the
conduct of prospective clinical research in HCC.
Criteria for eligibility:
Study pop:
Participants with hepatocellular carcinoma who have received immunotherapy based
neoadjuvant or conversion therapy
Sampling method:
Non-Probability Sample
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. Received immunotherapy based neoadjuvant or conversion therapy.
4. Complete recovery from surgical resection within 4 weeks prior to enrollment.
5. Child Pugh liver function rating A or B (≤ 7 points).
6. ECOG PS score was 0-1 points.
7. Expected survival time ≥ 12 weeks.
8. 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.
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. Participants who are preparing to undergo or have previously received organ or
allogeneic bone marrow transplantation.
4. 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, 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
5. 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.
6. 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.
7. 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.
8. 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).
9. History of spontaneous rupture of liver tumors.
10. Individuals with a history of hepatic encephalopathy.
11. Congenital or acquired immune dysfunction in subjects (such as HIV infected
individuals).
12. 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.
13. 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.)
14. Within 6 months prior to the start of treatment, there have been abdominal fistulas,
gastrointestinal perforation, or abdominal abscesses.
15. Severe, unhealed or cracked wounds, as well as active ulcers or untreated fractures.
16. 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.
17. Major vascular diseases (such as aortic aneurysm requiring surgical repair or recent
peripheral arterial thrombosis) occur within 6 months prior to the surgery.
18. Severe infection within 4 weeks prior to the surgery, 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).
19. Use immunosuppressive agents or systemic hormone therapy within 14 days prior to the
surgery to achieve immunosuppressive effects (dose>10mg/day prednisone or other
therapeutic hormones).
20. Received attenuated live vaccine treatment within 28 days prior to the surgery.
21. 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
Start date:
April 1, 2014
Completion date:
August 3, 2026
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/NCT06571396
