Trial Title:
Neoadjuvant IMRT Combined With Camrelizumab and Apatinib for Resectable HCC With PVTT
NCT ID:
NCT06349317
Condition:
Hepatocellular Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Apatinib
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:
Combination Product
Intervention name:
Neoadjuvant intensity-modulated radiotherapy combined with perioperative camrelizumab and apatinib
Description:
1. Preoperative IMRT targeting PVTT and intrahepatic tumor lesions with a prescribed
dose for 18Gy in 6 fractions delivered by using 6-MV X-rays with a linear
accelerator at 5 fractions per week;
2. Perioperative combination of camrelizumab and apatinib Preoperatively, camrelizumab
(200mg, every 2 weeks) combined with apatinib (250mg, daily) for 2 cycles (2 weeks
as one cycle); Postoperatively, camrelizumab (200mg, every 3 weeks) combined with
apatinib (250mg, daily) for 8 cycles (3 weeks as one cycle).
Arm group label:
Neoadjuvant intensity-modulated radiotherapy combined with perioperative camrelizumab and apatinib
Summary:
This study is an open-label, single-arm prospective clinical trial that evaluates the
efficacy and safety of neoadjuvant intensity-modulated radiotherapy combined with
perioperative camrelizumab and apatinib in the treatment of resectable hepatocellular
carcinoma with portal vein tumor thrombus.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Signed written informed consent and able to comply with scheduled visits and related
procedures;
2. Age ≥18 and ≤75 years, regardless of gender;
3. Patients with HCC who meet the clinical diagnostic criteria of China's "Guidelines
for the Diagnosis and Treatment of Hepatocellular Carcinoma" (2022 Edition) or are
diagnosed by biopsy, and have at least one measurable lesion according to the
mRECIST criteria;
4. Presence of portal vein tumor thrombus (PVTT) of Cheng's type I/II/III, with the
primary tumor being resectable;
5. Child-Pugh score of Class A;
6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1;
7. No prior antitumor treatment (such as surgery, radiotherapy, TACE, ablation,
chemotherapy, targeted therapy, immunotherapy, or systemic therapy).
8. For patients with hepatitis B virus (HBV) infection, testing for HBV-DNA is
required; direct treatment initiation is allowed if HBV-DNA ≤2000 IU/mL; if HBV-DNA
>2000 IU/mL, antiviral therapy should be administered for one week before starting
the treatment; all HBV positive patients will receive continuous antiviral treatment
throughout the study; patients with hepatitis C virus (HCV) RNA positive must
undergo antiviral treatment as per the guidelines;
9. Participants must provide a fresh tumor biopsy sample during the screening period
(can be waived after discussion with the medical monitor) and blood samples for
monitoring immune cells, cytokine levels, and other relevant immune status in the
tumor microenvironment;
10. Expected survival of ≥12 weeks;
11. Adequate organ and marrow function, as defined by the following laboratory values:
1. Hematology: Absolute Neutrophil Count ≥1.5×109/L; Platelets ≥80×109/L;
Hemoglobin ≥90g/L;
2. Liver function: Total bilirubin ≤3× upper limit of normal (ULN); Alanine
Aminotransferase and Aspartate Aminotransferase ≤5×ULN; Serum albumin ≥30g/L;
3. Renal function: Serum creatinine (Cr) ≤1.5×ULN, or for patients with Cr
>1.5×ULN, creatinine clearance (CCr) ≥45 mL/min (Cockcroft-Gault formula);
Urinalysis showing proteinuria <2+; For participants with baseline proteinuria
≥2+, a 24-hour urine collection and quantitative protein <1g is required;
4. Coagulation: International Normalized Ratio or APTT ≤1.5×ULN;
12. Females of childbearing potential must agree to abstain from heterosexual
intercourse or use effective contraception from signing the informed consent until
at least 120 days after the last dose of study medication. They must have a negative
serum HCG test within 1 week before treatment and must not be breastfeeding. Females
who have not reached menopause (≥12 months of amenorrhea without an alternative
medical cause) and have not undergone sterilization (e.g., hysterectomy, bilateral
salpingectomy, or bilateral oophorectomy) are considered to be of childbearing
potential;
13. Male participants with partners of childbearing potential must agree to abstain from
heterosexual intercourse or use reliable and effective contraceptive methods from
the time of signing the informed consent until at least 120 days after the last dose
of study medication. During the same period, male participants must also agree not
to donate sperm. Male subjects whose partners are pregnant must use condoms and do
not need to use other contraceptive methods.
Exclusion Criteria:
1. PVTT located in the portal vein branch opposite the tumor, or with inferior vena
cava tumor thrombus, extrahepatic metastasis, or tumor invasion of adjacent organs;
2. Known intrahepatic cholangiocarcinoma, sarcomatoid HCC, mixed-cell carcinoma, and
fibrolamellar carcinoma; active malignant tumors other than HCC within the past 5
years or concurrently, except for cured localized tumors such as basal cell
carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder
cancer, prostate carcinoma in situ, cervical carcinoma in situ, and breast carcinoma
in situ, which are allowed;
3. Currently with interstitial pneumonia or interstitial lung disease, or history of
interstitial lung disease requiring hormone treatment, or other conditions that may
interfere with the judgement and management of immunotherapy-related pulmonary
toxicity, such as pulmonary fibrosis, organizing pneumonia (e.g., obliterative
bronchiolitis), pneumoconiosis, drug-related pneumonia, idiopathic pneumonia, or
participants with active pneumonia or severe impairment of lung function shown on a
chest CT during screening; active tuberculosis;
4. Active autoimmune disease or history of autoimmune disease that may recur, including
but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis,
hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism (patients
controllable with hormone replacement therapy are allowed); Patients with skin
conditions that do not require systemic treatment, such as vitiligo, psoriasis, and
alopecia, those with controlled Type I diabetes mellitus undergoing insulin therapy,
or individuals whose childhood asthma has fully resolved with no need for
intervention in adulthood, are allowed; patients requiring bronchodilators for
medical intervention of asthma are not allowed;
5. Use of immunosuppressive drugs or systemic corticosteroids for the purpose of
immunosuppression (dose >10mg/day of prednisone or equivalent) within 2 weeks before
the start of the study;
6. Active infection, fever of unknown origin ≥38.5°C within 1 week before the study
start, or baseline white blood cell count >15×10^9/L; therapeutic antibiotics orally
or intravenously within 2 weeks before the study start (excluding prophylactic
antibiotics given IV for no more than 48 hours);
7. Congenital or acquired immunodeficiency (e.g., HIV infection);
8. Receipt of live attenuated vaccines within 4 weeks before the study start or
expectation of needing such vaccines during the camrelizumab treatment period or
within 60 days after the last dose of camrelizuma;
9. Significant bleeding symptoms of clinical significance or a clear bleeding tendency
within 6 months before the study start, such as gastrointestinal bleeding,
hemorrhagic gastric ulcers, or vasculitis; if baseline fecal occult blood is
positive, retesting is allowed, and if still positive, gastroduodenoscopy is
required;
10. Known genetic or acquired bleeding (e.g., coagulopathy) and thrombotic tendencies,
such as hemophilia, coagulation mechanism disorders, thrombocytopenia, etc.;
currently receiving full-dose oral or injectable anticoagulants or thrombolytic
agents for therapeutic purposes (prophylactic use of low-dose aspirin, etc., is
allowed);
11. Arterial thromboembolic events within 6 months before the study start, such as
cerebrovascular accidents (including transient ischemic attacks, cerebral
hemorrhage, cerebral infarction), CTCAE grade 3 or above deep vein thrombosis,
pulmonary embolism, etc;
12. Uncontrolled clinical symptoms or diseases of the heart, such as: (1) heart failure
of NYHA class II or above or echocardiography showing LVEF <50%; (2) unstable
angina; (3) myocardial infarction within 1 year before treatment; (4) clinically
significant supraventricular or ventricular arrhythmias requiring treatment or
intervention; (5) QTc > 450ms for males and >470ms for females (QTc interval
calculated using the Fridericia formula; if QTc is abnormal, continuous testing
three times at 2-minute intervals is allowed, taking the average value);
13. Hypertension not well controlled with antihypertensive medication (systolic blood
pressure ≥140mmHg or diastolic blood pressure ≥90mmHg based on the average of ≥2
blood pressure readings), allowing achievement of the above parameters through
antihypertensive treatment; history of hypertensive crisis or hypertensive
encephalopathy;
14. Major vascular diseases within 6 months before the study start (e.g., requiring
surgical repair or recent peripheral arterial thrombosis of an aneurysm);
15. Severe, unhealed, or open wounds and active ulcers or untreated fractures;
16. Major surgery (excluding diagnostic) within 4 weeks before the study start;
17. Inability to swallow pills, malabsorption syndrome, or any condition affecting
gastrointestinal absorption;
18. Intestinal obstruction and/or clinical signs or symptoms of gastrointestinal
obstruction, including partial obstructions requiring parenteral hydration,
parenteral nutrition, or tube feeding related to the underlying disease, within 6
months before the study start. Patients with incomplete obstruction/obstruction
syndrome/intestinal obstruction signs/symptoms at initial diagnosis who have
undergone definitive (surgical) treatment to alleviate symptoms may be eligible for
the study;
19. Use of strong CYP3A4/CYP2C19 inducers, including rifampin (and its analogs) and
Hypericum perforatum, or strong CYP3A4/CYP2C19 inhibitors within 2 weeks before the
study start;
20. Known allergy to any monoclonal antibody, antiangiogenic targeted drugs, or
excipients;
21. Participation in other drug clinical studies within 12 weeks before the study start.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Mengchao Hepatobiliary Hospital, Fujian Medical University
Address:
City:
Fuzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Yong yi Zeng
Start date:
April 22, 2024
Completion date:
June 2026
Lead sponsor:
Agency:
Yongyi Zeng
Agency class:
Other
Source:
Meng Chao Hepatobiliary Hospital of Fujian Medical University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06349317
