Trial Title:
Clinical Study of Radiotherapy Combined With Camrelizumab and Apatinib in the Treatment of Liver Cancer Patients .
NCT ID:
NCT06632522
Condition:
Liver Cancer
Conditions: Official terms:
Liver Neoplasms
Apatinib
Conditions: Keywords:
Combined with portal vein tumor thrombus,VP4
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:
radiotherapy combined with Camrelizumab and Apatinib
Description:
Camrelizumab is administered intravenously (without preventive medication), with a fixed
dose of 200mg, with an infusion of 30 min (not less than 20 min and not more than 60 min)
every three weeks. Apatinib, 250 mg, taken orally within half an hour after meals, QD,
continuously.
Arm group label:
radiotherapy combined with Camrelizumab and Apatinib
Summary:
Clinical study of radiotherapy combined with Camrelizumab and Apatinib in the treatment
of liver cancer patients with VP4.
Detailed description:
This study is a single-arm, open, prospective and multi-center clinical study, aiming at
observing and evaluating the efficacy and safety of radiotherapy combined with
Camrelizumab and apatinib in the treatment of patients with VP4 liver cancer.
Criteria for eligibility:
Criteria:
Inclusion Criteria：
1. Patients volunteered to join this study and signed informed consent;
2. ≥18 years old, both men and women;
3. Patients with hepatocellular carcinoma diagnosed by CT/MRI;
4. Clinical liver cancer in Barcelona is stage C with portal vein tumor thrombus (PVTT,
VP4), which is not suitable for operation or local treatment, or progresses after
operation and/or local treatment;
5. For patients who have progressed after local treatment, local treatment (including
but not limited to surgery, hepatic artery embolization, TACE, hepatic artery
perfusion, radiofrequency ablation, cryoablation or percutaneous ethanol injection)
has been completed at least 4 weeks before the baseline imaging scan, and the toxic
reactions caused by local treatment (except alopecia) must be restored to the rating
of National Cancer Institute-General Terminology for Adverse Events (NCI-CTCAE
v5.0).
6. Never received any systematic treatment for HCC before;
7. Except for tumor thrombus, the number of intrahepatic and extrahepatic lesions is
≤10;
8. The diameter of extrahepatic lesions is ≤ 5 cm;
9. At least one measurable lesion (according to the requirements of RECISTv1.1, the
long diameter of the measurable lesion in spiral CT scanning is ≥10 mm or the short
diameter of swollen lymph nodes is ≥15 mm; Lesions that have received local
treatment in the past (except radiotherapy for target lesions) can be used as target
lesions after they are clearly advanced according to RECIST v1.1 standard);
10. Child-Pugh liver function classification is Grade A or Grade B (score ≤7).
11. ECOG score: 0 ~ 1;
12. The expected survival time is ≥12 weeks;
13. The main organ functions meet the following requirements (within 7 days before the
start of the study and treatment):
(1) Routine blood examination: (Except hemoglobin, no blood transfusion, no use of
granulocyte colony stimulating factor [G-CSF] and no drug correction within 14 days
before screening): Absolute neutrophil count ≥1.5×109/L; Platelets ≥50×109/L; Hb ≥90 g/L;
(2) Biochemical examination: (albumin was not transfused within 14 days before
screening): Serum albumin ≥29 g/L; Serum total bilirubin ≤1.5× upper limit of normal
range (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase acidase
(AKP)≤5×ULN; Serum creatinine (Cr)≤1.5ULN or Cr clearance rate > 50 mL/min
(Cockcroft-Gault formula is as follows).
Male: Cr clearance rate =((140- age) × body weight) /(72× blood Cr) Female: Cr clearance
rate =((140- age )× body weight) /(72× blood Cr) × 0.85 body weight unit: kg; Blood Cr
unit: mg/mL; (3) The international normalized ratio (INR) is ≤ 2.3 or the prothrombin
time (PT) exceeds the range of normal control for ≤6 seconds; (4) Urinary protein < 2+
(if urinary protein ≥2+, 24-hour (h) urinary protein quantification can be performed, and
24-hour urinary protein quantification < 1.0 g can be enrolled).
14. If the patient suffers from active hepatitis B virus (HBV) infection, the HBV-
deoxyribonucleic acid (DNA) must be less than 500 IU/mL (if the research center only
has a copy/mL detection unit, it must be less than 2500 copy/mL), and he must
receive anti-HBV treatment (according to local standard treatment, such as
entecavir) for at least 14 days before the start of the research treatment, and he
is willing to take the whole course during the research period. Hepatitis C virus
(HCV) ribonucleic acid (RNA) positive patients must receive antiviral treatment
according to local standard treatment guidelines, and their liver function should be
within the level 1 increase of CT CAE.
Fertile women: they must agree to abstain from sex (avoid heterosexual intercourse) or
use reliable and effective methods of contraception for at least 120 days from signing
the informed consent form until the last administration of the study drug. And the serum
HCG test must be negative within 7 days before the start of the study treatment; And must
be non-lactating. If a female patient has menstruated, has not yet reached the
post-menopausal state (continuous non-menstrual period ≥12 months, and no other reasons
have been found except menopause), and has not undergone sterilization surgery (such as
hysterectomy, bilateral tubal ligation or bilateral oophorectomy), it is considered that
the patient has fertility. For male patients whose partner is a woman of childbearing
age, they must agree to abstain from sex for at least 120 days from signing the informed
consent form until the last administration of the study drug, or to use reliable and
effective methods for contraception. Male subjects must also agree not to donate sperm
during the same period. Male subjects whose partners are pregnant must use condoms, and
no other contraceptive methods are needed.
Exclusion Criteria：
1. Known hepatobiliary cell carcinoma, sarcomatoid HCC, mixed cell carcinoma and
fibreboard cell carcinoma; Have other active malignant tumors except HCC within 5
years or at the same time. Localized tumors that have been cured, such as basal cell
carcinoma of skin, squamous cell carcinoma of skin, superficial bladder cancer,
prostate cancer in situ, cervical cancer in situ, breast cancer in situ, etc., can
be included in the group;
2. The tumor thrombus occupies all the portal vein lumen;
3. Except for tumor thrombus, the number of intrahepatic and extrahepatic lesions is
more than 10;
4. The diameter of extrahepatic lesions is more than 5 cm;
5. Patients who are ready to undergo or have previously received organ or allogeneic
bone marrow transplantation;
6. Moderate and severe ascites with clinical symptoms (except for those who only show a
small amount of ascites on imaging but are not accompanied by clinical symptoms);
Uncontrolled or moderate or above pleural effusion and pericardial effusion;
7. Patients who have a history of gastrointestinal bleeding or have a clear tendency of
gastrointestinal bleeding within 6 months before the start of the study and
treatment, such as: bleeding-risk or severe esophageal and gastric varices, local
active gastrointestinal ulcer lesions, and persistent fecal occult blood positive,
can not be included in the group (if the fecal occult blood is positive in the
baseline period, it can be rechecked, and if it is still positive after the recheck,
it needs to undergo gastroduodenoscopy (EGD), and if the EGD indicates bleeding-risk
esophageal and gastric varices, it can not be included).
8. Abdominal fistula, gastrointestinal perforation or abdominal abscess occurred within
6 months before the start of the study treatment;
9. Known hereditary or acquired bleeding (such as coagulation dysfunction) or
thrombotic tendency, such as hemophilia patients; At present, or in the near future
(within 10 days before the start of the study treatment), full-dose oral or
injection anticoagulants or thrombolytic drugs have been used for therapeutic
purposes (low-dose aspirin and low-molecular-weight heparin are allowed for
preventive use);
10. Aspirin (> 325 mg/ day (maximum antiplatelet dose) or dipyridamole, ticlopidine,
clopidogrel and cilostazol are currently being used or recently used (within 10 days
before the start of the study treatment);
11. Thrombosis or embolism occurred within 6 months before the start of study treatment,
such as cerebrovascular accident (including transient ischemic attack, cerebral
hemorrhage, cerebral infarction) and pulmonary embolism;
12. There are clinical symptoms or diseases of the heart that can't be well controlled,
such as: (1) according to the standards of new york Heart Association (NYHA) (see
Annex 5), the cardiac insufficiency is above grade 5)II or the left ventricular
ejection fraction (LVEF) is less than 50%; (2) Unstable angina pectoris; (3)
myocardial infarction occurred within one year before the start of study and
treatment; (4) Clinically significant supraventricular or ventricular arrhythmia
needs treatment or intervention; (5)QTc > 450ms (male); QTc > 470ms (female) (QTc
interval is calculated by Fridericia formula; If the QTc is abnormal, it can be
continuously tested for three times every 2 minutes, and the average value can be
taken);
13. Suffering from high blood pressure, which cannot be well controlled by
antihypertensive drugs (systolic blood pressure ≥140 mmHg or diastolic blood
pressure ≥90 mmHg) (based on the average of BP readings obtained by ≥2
measurements), it is allowed to realize the above parameters by using
antihypertensive therapy; Hypertensive crisis or hypertensive encephalopathy has
occurred in the past;
14. Major vascular diseases (for example, aortic aneurysm requiring surgical repair or
recent peripheral artery thrombosis) occurred within 6 months before the start of
study treatment;
15. Severe, unhealed or split wounds and active ulcers or untreated fractures;
16. Received major surgical treatment (except diagnosis) within 4 weeks before the start
of the study treatment or expected major surgical treatment during the study period;
17. Can't swallow pills, malabsorption syndrome or any condition that affects
gastrointestinal absorption;
18. Have suffered from intestinal obstruction and/or clinical signs or symptoms of
gastrointestinal obstruction within 6 months before starting the study and
treatment, including incomplete obstruction related to the original disease or
requiring routine parenteral hydration, parenteral nutrition or tube feeding:
19. At the initial diagnosis, patients with incomplete obstruction/obstruction
syndrome/signs/symptoms of intestinal obstruction may be enrolled in the study if
they receive definite (surgical) treatment to relieve symptoms;
20. There is evidence that there is pneumoperitoneum that cannot be explained by
puncture or recent surgical operation;
21. Past or present central nervous system metastasis;
22. Metastatic diseases involving major airways or blood vessels (for example, portal
vein trunk or vena cava that is completely occluded due to tumor invasion needs to
be excluded, portal vein trunk refers to the confluence of splenic vein and superior
mesenteric vein and the branch where hepatic portal vein divides into left and right
branches) or large mediastinal tumor mass in the center (< 30 mm from carina);
23. Those with a history of hepatic encephalopathy;
24. At present, patients with interstitial pneumonia or interstitial lung disease, or
patients with previous history of interstitial pneumonia or interstitial lung
disease requiring hormone therapy, or other subjects with pulmonary fibrosis,
organized pneumonia (for example, bronchiolitis obliterans), pneumoconiosis,
drug-related pneumonia, idiopathic pneumonia, or subjects with evidence of active
pneumonia or severe impairment of lung function on chest computed tomography (CT)
during screening period are allowed to have radiation fields. Active tuberculosis;
25. Active autoimmune disease or history of autoimmune disease and possible recurrence
(including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis,
enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism
[subjects who can only be controlled by hormone replacement therapy can be
included]); Subjects suffering from skin diseases without systematic treatment, such
as vitiligo, psoriasis, alopecia, controlled type I diabetes treated with insulin or
asthma in childhood have been completely relieved, and adults can be included
without any intervention; Asthmatic patients who need bronchodilators for medical
intervention cannot be included;
26. Use immunosuppressant or systemic hormone therapy within 14 days before starting the
study treatment to achieve the purpose of immunosuppression (dosage > 10mg/ day of
prednisone or other therapeutic hormones);
27. Strong CYP3A4/ CYP2C19 inducers used within 14 days before starting the study
treatment include rifampicin (and its analogues) and Hypericum perforatum or strong
CYP3A4/ CYP2C19 inhibitors;
28. It is known that there is a serious allergic history to any monoclonal antibody and
anti-angiogenesis targeted drugs;
29. Severe infection within 4 weeks before the start of study treatment, including but
not limited to hospitalization due to infection, bacteremia or complications of
severe pneumonia; Therapeutic antibiotics were given orally or intravenously within
2 weeks before the start of the study treatment (patients receiving preventive
antibiotics (for example, patients who prevent urinary tract infection or
exacerbation of chronic obstructive pulmonary disease are eligible to participate in
the study); 30 patients with congenital or acquired immune deficiency (such as HIV
infection);
31. Co-infection with hepatitis B and hepatitis C; 32. Previously received other
anti-PD-1 antibody therapy or other immunotherapy against PD-1/PD-L1, or previously
received apatinib and sorafenib therapy; 33. Palliative radiotherapy for non-target
lesions allowed to control symptoms must be completed at least 2 weeks before the
start of the study treatment, and the adverse events caused by radiotherapy have not
recovered to ≤ CTCAE level 1; 34. Received live attenuated vaccine treatment within
28 days before the start of the study treatment, or expected to be vaccinated during
the treatment period of Karelizumab or within 60 days after the last dose of
Karelizumab; 35. Have received other experimental drugs within 28 days before
starting the study treatment; According to the researcher's judgment, the patient
has other factors that may affect the research results or lead to the forced
termination of this study, such as alcoholism, drug abuse, other serious diseases
(including mental illness) that need to be treated together, serious laboratory
abnormalities, family or social factors, which will affect the safety of the
patient.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Beijing Tsinghua Chang Gung Hospital
Address:
City:
Beijing
Country:
China
Contact:
Last name:
Gong Li, M.A.
Phone:
13366061906
Email:
lga02375@btch.edu.cn
Start date:
October 20, 2024
Completion date:
December 30, 2026
Lead sponsor:
Agency:
Beijing Tsinghua Chang Gung Hospital
Agency class:
Other
Source:
Beijing Tsinghua Chang Gung Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06632522
