Trial Title:
Sintilimab+Bevacizumab+TACE vs. Lenvatinib+TACE for Advanced HCC
NCT ID:
NCT05985798
Condition:
Hepatocellular Carcinoma Non-resectable
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Chlorotrianisene
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Sin-Bev-TACE
Description:
Sintilimab (200mg I.V. q3w) and bevacizumab (7.5mg/kg I.V. q3w) are administered at 3-7
days after the first TACE. The study treatment of sintilimab and bevacizumab will last up
to 24 months. TACE can be repeated on demand.
Arm group label:
Sin-Bev-TACE
Intervention type:
Drug
Intervention name:
Len-TACE
Description:
Lenvatinib 12mg (body weight ≥60kg) or 8mg (body weight <60kg) P.O. qd will be started at
3-7 days after the first TACE. TACE will be repeated on demand.
Arm group label:
Len-TACE
Summary:
This study is conducted to evaluate the efficacy and safety of sintilimab, bevacizumab
plus TACE (Sin-Bev-TACE) compared with lenvatinib plus TACE (Len-TACE) for patients with
advanced stage hepatocellular carcinoma (HCC).
Detailed description:
This is a multicenter, prospective and randomized controlled trial to evaluate the
efficacy and safety of Sin-Bev-TACE versus Len-TACE for patient with advanced HCC.
258 patients with advanced HCC (BCLC C stage) will be enrolled in this study. The
patients will receive either sintilimab and bevacizumab (Sin-Bev) or lenvatinib (Len)
after first TACE using an 1:1 randomization scheme. In the Sin-Bev-TACE arm, sintilimab
(200mg I.V. q3w) and bevacizumab (7.5mg/kg I.V. q3w) will be started at 3-7 days after
the first TACE. In the the Len-TACE arm, lenvatinib 12mg (body weight ≥60kg) or 8mg (body
weight <60kg) P.O. qd will be started at 3-7 days after the first TACE.
TACE will be repeated on demand based on the evaluation of follow-up laboratory and
imaging examination. Sintilimab and bevacizumab will last up to 24 months, or until
disease progresses, intolerable toxicity, withdrawal of informed consent, loss of
follow-up, death, or other circumstances that require termination of treatment, whichever
occurs first. Lenvatinib will last until disease progresses, intolerable toxicity,
withdrawal of informed consent, loss of follow-up, death, or other circumstances that
require termination of treatment, whichever occurs first. In the Sin-Bev-TACE arm,
patients will be allowed to have sintilimab or bevacizumab as a sigle agent and will be
still considered on study when the other drug cause intolerable toxicity.
The primary end point of this study is overall survival (OS). The secondary endpoints are
progression-free survival (PFS), objective response rate (ORR), disease control rate
(DCR), and adverse events (AEs).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Advanced HCC (BCLC stage C) with diagnosis confirmed pathologically or clinically
- Disease amenable to TACE
- No prior systemic therapy, TACE, transcatheter arterial radioembolization (TARE),
transcatheter arterial embolization (TAE), hepatic arterial infusion chemotherapy
(HAIC) or radiation therapy for HCC
- Child-Pugh class A
- Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1
- Life expectancy of at least 3 months
- At least one measurable intrahepatic lesion
- Adequate organ and hematologic function
- Patients with active hepatitis B are allowed, but they need to receive antiviral
treatment to achieve a HBV DNA<10^2 IU/mL
- Patients with hepatitis C need to finish the anti-HCV treatment
Exclusion Criteria:
- Tumor thrombus involving main portal vein or both the first left and right branch of
portal vein
- Vena cava invasion
- Central nervous system metastasis
- History of hepatic encephalopathy
- History of organ and cell transplantation
- Uncontrolled ascites, hydrothorax or pericardial effusion
- Prior esophageal and/or gastric varices bleeding within 6 months prior to initiation
of study treatment
- Presence of known severe (G3) varicose veins in endoscopy within 3 months before the
first dose. Evidence of portal hypertension (including the finding of splenomegaly
in imaging studies) with a high risk of bleeding assessed by the investigator
- Presence of any life-threatening bleeding events within the past 3 months, including
the need for transfusion, surgery or local treatment, and continuous medication
therapy
- Any arterial or venous thromboembolic events within 6 months, including myocardial
infarction, unstable angina, cerebrovascular accident or transient cerebral ischemic
attack, pulmonary embolism, deep vein thrombosis, or any other history of serious
thromboembolism. Presence of implantable venous port or catheter-derived thrombosis,
or superficial venous thrombosis, barring stable thrombosis following the
conventional anticoagulation treatment. Prophylactic use of low-dose
low-molecular-weight heparin (e.g., enoxaparin 40 mg/day) is permitted.
- A 10-day consecutive dosing of aspirin (> 325 mg/day) or other drugs, e.g.,
dipyridamole and clopidogrel, known to inhibit the platelet function within 2 weeks
before the first dose
- Uncontrolled hypertension after the optimal medical treatment, history of
hypertensive crisis or hypertensive encephalopathy.
- Symptomatic congestive cardiac failure (NYHA Class II-IV). Symptomatic or poorly
controlled arrhythmia. History of congenital long QT syndrome or corrected QTc > 500
ms (calculated using Fridericia formula) during screening
- Serious hemorrhagic tendency or coagulopathy, or currently receiving thrombolytic
therapy
- History of gastrointestinal perforation and/or fistula, history of bowel obstruction
(including incomplete bowel obstruction requiring parenteral nutrition), extensive
bowel resection (partial colectomy or extensive small bowel resection accompanied
with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea
within the past 6 months
- History or current experience of pulmonary fibrosis and such lung diseases as
interstitial pneumonia, pneumoconiosis, drug-related pneumonia, and severely
impaired lung function
- Active tuberculosis (TB), currently receiving anti-tuberculosis treatment or
received such treatment within 1 year before the first dose
- Human immunodeficiency virus (HIV) infected (HIV 1/2 antibody positive) and known
syphilis infection requiring treatment
- Active or poorly clinically controlled serious infections. Severe infections within
4 weeks before the first dose, including but not limited to hospitalization caused
by infection, bacteremia, or severe pneumonia complication
- Presence of active autoimmune diseases requiring systemic treatment (e.g., use of
disease-modifying drugs, corticosteroids, or immunosuppressants) within 2 years
before the first dose. Use of alternative therapies (e.g., thyroxine, insulin, or
physiological corticosteroids for adrenal or pituitary insufficiency) is permitted.
Known history of primary immunodeficiency diseases. For patients with positive
autoimmune antibodies only, they should be assessed by the investigator to determine
whether they had an autoimmune disease
- Receipt of immunosuppressants within 4 weeks before the first dose, excluding local
glucocorticoids administered by nasal, inhaled, or other topical routes, or systemic
glucocorticoids of physiological doses (no more than 10 mg/day of prednisone or
equivalents), while the temporary use of glucocorticoids for preventing allergies or
treating dyspneic symptoms of such diseases as asthma and chronic obstructive
pulmonary disease is permitted
- Receipt of major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks
before the first dose or having unhealed wounds, ulcers, or fractures. Receipt of
tissue biopsy or other minor surgeries within 7 days before the first dose, barring
venipuncture and catheterization for intravenous infusion.
- Receipt of systemic treatment with traditional Chinese medicines with cancer
indications or immunomodulators (including thymosin, interferon, and interleukin,
barring local use for controlling pleural fluid or ascites) within 2 weeks before
the first dose
- History of malignancy other than HCC
- Known hypersensitivity to any ingredients in sintilimab, bevacizumab and lenvatinib
preparations or previous severe hypersensitivity reactions to other monoclonal
antibodies
- Pregnant or breastfeeding female patients
- Acute or chronic diseases, psychiatric disorders, or laboratory abnormalities that
may lead to the following consequences: increased study participation or
drug-related risks, or interference with interpreting trial results, and considered
ineligible for participating in the trial by the investigator
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
the Second Affiliated Hospital of Guangzhou Medical University
Address:
City:
Guangzhou
Zip:
510260
Country:
China
Status:
Recruiting
Contact:
Last name:
Mingyue Cai, Dr.
Phone:
+86-20-34156205
Email:
cai020@yeah.net
Contact backup:
Last name:
Kangshun Zhu, Dr.
Phone:
+86-20-34156205
Email:
zhksh010@163.com
Start date:
August 1, 2023
Completion date:
July 31, 2027
Lead sponsor:
Agency:
Second Affiliated Hospital of Guangzhou Medical University
Agency class:
Other
Collaborator:
Agency:
Affiliated Hospital of Guangdong Medical University
Agency class:
Other
Collaborator:
Agency:
Zhongshan People's Hospital, Guangdong, China
Agency class:
Other
Collaborator:
Agency:
Lecong Hospital, Shunde District, Foshan
Agency class:
Other
Collaborator:
Agency:
First People's Hospital of Foshan
Agency class:
Other
Collaborator:
Agency:
Affiliated Cancer Hospital & Institute of Guangzhou Medical University
Agency class:
Other
Source:
Second Affiliated Hospital of Guangzhou Medical University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05985798
