Study on the Safety and Efficacy of Donafinib Combined With Anti-PD-1 Antibody as Adjuvant Therapy for HCC Patients

  • STATUS
    Recruiting
  • participants needed
    30
  • sponsor
    Zhejiang University
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Updated on 16 February 2024
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cancer
blood transfusion
platelet count
corticosteroids
immunomodulator
stroke
serum pregnancy test
metastasis
neutrophil count
anticoagulants
hypertension
heart failure
antiviral drugs
antiviral therapy
granulocyte colony stimulating factor
carcinoma
sorafenib
hepatitis b surface antigen
hepatitis
encephalopathy
adjuvant therapy
aptt
thrombosis
postoperative complications
hepatectomy
ascites
pd-l1
hepatocellular carcinoma
mental illness
prothrombin
recurrent tumor
coagulopathy
tumor thrombosis
gastrointestinal hemorrhage
donafenib

Summary

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, with more than 700,000 new cases in the world every year. China has the highest incidence and death rate of HCC in the world, accounting for 55% of the world's annual incidence and 45% of the world's annual deaths. At present, surgical resection is still one of the most effective treatments for HCC. However, the recurrence rate of tumor after hepatectomy is still very high, and the recurrence rate of 5 years is 60~70%. Especially in patients with high-risk recurrence factors, without intervention, the cumulative recurrence rate in the first year was about 50%, about 60% in the second year, about 70% in the third year, and about 80% in the fifth year. Tumor recurrence is an important bottleneck that hinders the long-term survival of patients. Therefore, there is an urgent need for effective adjuvant therapy to reduce the postoperative recurrence rate of patients with HCC, especially high-risk patients. However, there is still a lack of standard protocols for postoperative adjuvant therapy for HCC. Here investigators intend to explore the safety and efficacy of Donafinib Combined With Anti-PD-1 Antibody as postoperative adjuvant therapy for HCC patients with high risks of recurrence.

Description

This is a single center, open, single arm, and exploratory study. Thirty HCC patients with high risk recurrence factors after radical surgery will be enrolled. Adjuvant treatment of Donafenib combined with anti-PD-1 antibody will be given for 6 months. The primary endpoint is the cumulative percentage of patients without recurrence in the first year. The recurrence-free survival (RFS), overall survival (OS), tumor recurrence time (TTR), ECOG physical condition (ECOG PS) score, the changes of FACT-Hep based quality of life score, changes of AFP, and adverse events will be recorded and analyzed, to evaluated the efficacy and safety of this combination treatment.

Details
Condition Adenocarcinoma, Adenocarcinoma, HEPATIC NEOPLASM, liver cancer, HEPATOCELLULAR CARCINOMA, liver cancer
Age 18years - 75years
Treatment Donafenib and anti-PD-1 antibody
Clinical Study IdentifierNCT04418401
SponsorZhejiang University
Last Modified on16 February 2024

Eligibility

 Yes No Not Sure

Inclusion Criteria

)Voluntary admission and signature of written informed consent
)18~75 years of age (including 75 years), male and female
)Hepatocellular carcinoma underwent radical resection 4~8 weeks before
enrolled
)Pathologically diagnosed as hepatocellular carcinoma with any of the
following conditions: a)Microvascular invasion (MVI); b)Satellite nodules were
found in specimens; c)Multiple tumor nodules(>3 nodules); d)Portal vein tumor
thrombosis (PVTT): The tumor thrombosis invades the left or right branches of
portal vein, with or without hepatic vein invasion
)4 weeks after radical resection, the imaging examination confirmed no
recurrence and metastasis
)Liver function Child-Pugh grade A (5~6)
)Physical condition was scored 0~1 according to the ECOG criteria
)Expected lifetime >3 months
)HBV DNA<10^4 copy/ ml (2000 IU/ ml); if HBV DNA 10^4 copy/ ml, antiviral
therapy should be given, until the HBV DNA drops below 10^4Copy/ml patient can
be enrolled in the study. And during the study, antiviral drugs should be
continued, and liver function and hepatitis B virus load should be monitored
)The results of the serum pregnancy test must be negative for women with
fertility (i.e. non-menopausal or surgical sterilization) within 7 days prior
to the study of drug administration
)The main organs function normally: Blood routine examination (no
transfusion, no use of G-CSF within 14 days before screening): a)Hemoglobin 90
g/L; b)Absolute neutrophil count (ANC)1.510^9/L; c)Platelet count 7510^9/L
Blood biochemical examination (albumin not used within 14 days before
screening): d)Albumin 28 g/L; e)Total bilirubin 1.5 ULN; f)Aspartate
aminotransferase (AST), alanine aminotransferase (ALT )3 ULN; g)Serum
creatinine 1.5ULN; Coagulation function: h)The international standardized
ratio (INR) or prothrombin time (PT )1.5ULN;. i)Activated partial
thromboplastin time (APTT )1.5ULN

Exclusion Criteria

Histopathological diagnosis of hepatocellular carcinoma - intrahepatic cholangiocarcinoma (HCC-ICC) mixed type
Positive resection margin or tumor rupture
Operation of recurrent liver cancer
Other malignancies within 5 years unless the patient has received a possible cure and there is no evidence of the disease within 5 years, but this time requirement (i.e. within 5 years) is not applicable to patients with skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ or other carcinoma in situ who have successfully undergone excision
Previous or present congenital or acquired immunodeficiency disease
Active or previously documented autoimmune or inflammatory diseases (including but not limited to: autoimmune hepatitis, interstitial pneumonia, inflammatory bowel disease, systemic lupus erythematosus, vasculitis, uveitis, pituitary inflammation, hyperthyroidism or hypothyroidism, asthma requiring treatment with bronchiectasis, etc.), asthma with vitiligo or which has been completely relieved in childhood without inclusion of any intervention in adults
History of severe mental illness
Suffer from diseases (e.g. severe vomiting, chronic diarrhea, intestinal obstruction, absorption disorders, etc.) that affect the absorption, distribution, metabolism or clearance of the study drug
Past or combined medication/treatment
\. Had major surgery (defined by the investigators) within 4 weeks before
admission, or expected to require major surgery during study therapy
\. Previous transplantation of allogeneic stem cells or parenchymal organs
\. Preoperative treatment with sorafenib, valvatinib, regofenib or
immunomodulator such as anti PD-1 PD-L1 anti CTLA-4
\. Patients who have received other systemic anti-tumor treatments before
surgery, including traditional Chinese medicine with anti-tumor indications
have had less than 2 weeks or 5 half-time (whichever is longer) between the
completion of the treatment and the use of the drugs before the study, or who
have not recovered to CTCAE 1 level of adverse events caused by preoperative
treatment
\. Other adjuvant therapy (except antiviral therapy) was performed after
operation
\. Systemic immunosuppressive drugs have been used within 2 weeks before
admission or are expected to be required during the study period, except in
the following cases: a)Intra-nasal, inhalation, topical or topical (e.g
intra-articular) corticosteroids; b)Prednisone 10 mg/day or other equivalent
systemic corticosteroid; c)Prophylactic use of corticosteroids for
hypersensitivity
\. Take drugs that may prolong QTc and/or induce advanced torsional
ventricular tachycardia (Tdp) or affect drug metabolism
\. Patients with known or suspected history of allergies to Donafenib or
similar drugs, hypersensitivity to chimeric or humanized antibodies or fusion
proteins, or to excipients used to study drugs
\. The presence of uncontrollable hepatic encephalopathy, hepatorenal
syndrome, ascites, pleural effusion or pericardial effusion
\. Active bleeding or abnormal coagulation function, bleeding tendency or
undergoing thrombolytic, anticoagulant or antiplatelet therapy
\. There was a history of gastrointestinal bleeding or a definite tendency
of gastrointestinal bleeding in the past 4 weeks (e.g. local active ulcer
lesions, stool occult blood ++ , e.g. continuous stool occult blood +
gastroscopy should be performed), or other conditions (e.g. severe gastric
fundus/esophageal varices) that the researchers determined might cause
gastrointestinal bleeding
\. Gastrointestinal perforation, abdominal fistula or abdominal abscess
occurred within 6 months
\. Thrombosis or thromboembolic events, such as stroke and/or transient
ischemic attack, deep vein thrombosis, pulmonary embolism, etc., occurred
within 6 months
\. With significant clinical significance, including but not limited to
previous 6 months of acute myocardial infarction, severe/unstable angina, or
coronary artery bypass grafting, congestive heart failure (New York Heart
Association NYHA Grade > Grade 2), Poor control or arrhythmia requiring
pacemaker therapy, Uncontrolled hypertension (systolic blood pressure 140 mmHg
and/or diastolic blood pressure 90 mmHg)
\. Active infections, including: a)HIV (HIV 1/2 antibody) positive; b)Active
hepatitis B (HBsAg positive and abnormal liver function); c)Active hepatitis C
(HCV antibody positive or HCV RNA10^3 copy/ ml and abnormal liver function)
d)Active tuberculosis; e)Other uncontrolled active infections (CTCAE V5.0>
level 2)
\. Other significant clinical and laboratory abnormalities, the researchers
believe affect safety evaluation, such as: uncontrolled diabetes, chronic
kidney disease, peripheral neuropathy (CTCAE V5.0) of grade II or above
thyroid dysfunction, etc
\. Has not recovered from surgery, such as the presence of unhealed
incisions or severe postoperative complications
\. Received any live attenuated vaccine within 4 weeks of admission or
during the study period
\. Pregnant or lactating women, as well as women or men with fertility who
are unwilling or unable to take effective contraception
\. A history of alcohol, psychotropic or other substance abuse within 6
months
\. Enrolled in other clinical trials within 4 weeks before admission
\. Failure to follow the study protocol for treatment or scheduled follow-
up
\. Any other factors evaluated by investigators that patients cannot be
enrolled
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cancer
blood transfusion
platelet count
corticosteroids
immunomodulator
stroke
serum pregnancy test
metastasis
neutrophil count
anticoagulants
hypertension
heart failure
antiviral drugs
antiviral therapy
granulocyte colony stimulating factor
carcinoma
sorafenib
hepatitis b surface antigen
hepatitis
encephalopathy
adjuvant therapy
aptt
thrombosis
postoperative complications
hepatectomy
ascites
pd-l1
hepatocellular carcinoma
mental illness
prothrombin
recurrent tumor
coagulopathy
tumor thrombosis
gastrointestinal hemorrhage
donafenib

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