Trial Title:
Combination Therapy of HAIC, Surufatinib and Tislelizumab for Unresectable or Metastatic Biliary Tract Cancer
NCT ID:
NCT06134193
Condition:
Carcinoma
Intrahepatic Cholangiocarcinoma
Gallbladder Cancer
Surufatinib
Angiogenesis Inhibitors
Tislelizumab
Antineoplastic Agents, Immunological
Immunotherapy
Conditions: Official terms:
Cholangiocarcinoma
Biliary Tract Neoplasms
Gallbladder Neoplasms
Tislelizumab
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:
HAIC
Description:
hepatic arterial infusion (HAI) of oxaliplatin, fluorouracil, leucovorin (FOLFOX)
treatment (Q3W) Oxaliplatin: 85mg/m2 , Day 1 Leucovorin: 200mg/m2, Day 1 Fluorouracil:
400mg/m2, Day1 and 2400mg/m2 continuous arterial perfusion for 46h.
Arm group label:
HAIC, surufatinib and tislelizumab
Intervention type:
Drug
Intervention name:
Surufatinib
Description:
250mg PO d1, Q3W
Arm group label:
HAIC, surufatinib and tislelizumab
Intervention type:
Drug
Intervention name:
Tislelizumab
Description:
200mg IV d1, Q3W
Arm group label:
HAIC, surufatinib and tislelizumab
Summary:
This is a single-arm, exploratory study to evaluate the efficacy and safety of HAIC in
combination with surufatinib and tislelizumab in the first line treatment of patients
with unresectable or metastatic biliary tract cancer
Criteria for eligibility:
Criteria:
Inclusion Criteria:
-
1. Written informed consent should be signed before implementing any trial-related
procedures 2. Patients with age ≥18 years ,≤75 years old. 3. ECOG PS scores 0-1
4. Histologically/cytologically confirmed unresectable or metastatic
Intrahepatic Cholangiocarcinoma and gallbladder cancer 5. Child Pugh stage A 6.
Estimated survival > 12 weeks 7. According to the diagnostic criteria of
NCCN(National Comprehensive Cancer Network ) guidelines for intrahepatic
cholangiocarcinoma and gallbladder cancer, the patients were diagnosed as
intrahepatic cholangiocarcinoma and gallbladder cancer not suitable for radical
resection: unable to obtain R0 resection, multiple liver, beyond hilar lymph
node metastasis and distant metastasis 8. No systemic therapy for unresectable
or metastatic biliary tract cancer; Patients who had received one regimen of
adjuvant therapy and had a relapse more than 6 months after the end of
chemotherapy were eligible.
9. At least one measurable lesion according to RECIST V1.1 The diameter of the
target lesion was ≥1cm as accurately measured by enhanced magnetic resonance
imaging (MRI) or enhanced computed tomography (CT), and the study target lesion
had not received previous local treatment (including but not limited to HAIC,
radiofrequency ablation, argon-helium knife, radiotherapy, and other local
treatment methods) 10. Sufficient organ and bone marrow functions, with the
laboratory test values within 14 days before the enrollment meeting the
following requirements (no blood components, cell growth factors, albumin, and
other drugs via intravenous or subcutaneous administrations are allowed for
correction treatment within the first 14 days after the laboratory test results
are obtained). The specific information is as follows:
1. Routine blood test: white blood cell ≥ 4.0 × 109/L absolute neutrophil count
(ANC) ≥ 1.5 × 109/L; platelet count (PLT) ≥ 80 × 109/L; hemoglobin (HGB) ≥ 9.0
g/dL.
2. Hepatic function: total bilirubin (TBIL) ≤ 3 × upper limit of normal (ULN),
alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 × ULN.
3. Renal function: serum creatinine (Cr) ≤ 1.5 × ULN or eGFR≥60%,clearance of
creatinine (CCr) ≥ 60 mL/min (Cockcroft Gault formula);
4. Blood coagulation function: international normalized ratio (INR) and activated
partial thromboplastin time (APTT) ≤ 1.5 × ULN.
5. Normal cardiac function with left ventricular ejection fraction (LVEF)≥50%
measured by two-dimensional echocardiography; 11. Patients were eligible for
HAIC surgery as prespecified by the study center, without any
contraindications, and could receive HAIC treatment.
12. Male or female patients of childbearing potential volunteered to use an
effective method of contraception, such as dual barrier methods, condoms, oral
or injectable contraceptives, intrauterine devices, etc. during the study and
for 6 months after the last study medication. "All female patients will be
considered fertile unless they have undergone natural menopause, artificial
menopause, or sterilization (e.g., hysterectomy, bilateral adnophorectomy, or
radioactive ovarian irradiation)."
Exclusion Criteria:
-
1. Participated in other clinical trials of antineoplastic drugs within 4 weeks
before enrollment.
2. History of liver resection, TACE treatment, and any previous immune or targeted
therapy; 3. Liver metastases of 70% or more of the total liver volume as
determined by the investigator.
4. History of prior or planned any organ transplantation. 5. Patients with
obstructive jaundice who did not reduce jaundice as expected. 6. Other
malignant tumors in the past 5 years, excluding basal cell or squamous cell
carcinoma of the skin after radical surgery, or carcinoma in situ of the
cervix.
7. Patients with confirmed or suspected symptomatic active brain or meningeal
metastases.
8. Received any surgery (except biopsy) or invasive treatment or operation within
4 weeks before enrollment and the surgical incision was not completely healed
(except venous catheterization, puncture drainage, etc.).
9. Electrolyte abnormalities that were judged by the investigator to be clinically
significant..
10. Patients have current drug-uncontrolled hypertension defined as systolic blood
pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg.
11. Urine routine test showed urinary protein ≥2+, and 24 h urinary protein amount
>1.0g.
12. Patients whose tumors were judged by the investigator to be highly likely to
invade vital blood vessels and cause fatal bleeding during the follow-up study.
13. Patients with evidence or history of significant bleeding tendency within 3
months before enrollment (bleeding within 3 months >30 mL, hematemesis, melena,
hematochezia), hemoptysis (within 4 weeks>5 mL of fresh blood); Patients with a
history of hereditary or acquired bleeding or coagulopathy. Patients had
clinically significant bleeding symptoms or clear bleeding tendency within 3
months before enrollment, such as gastrointestinal bleeding, hemorrhagic
gastric ulcer, etc.
14. Clinically significant cardiovascular disease, including but not limited to
acute myocardial infarction, severe/unstable angina, or coronary artery bypass
grafting within 6 months before enrollment; New York Heart Association (NYHA)
classification of congestive heart failure >Grade 2; Ventricular arrhythmias
requiring medical therapy; Electrocardiogram (ECG) showed QT c interval ≥480
msec.
15. Women who are pregnant (with a positive pregnancy test before medication) or
breastfeeding.
16. Any other medical condition, clinically significant metabolic abnormality,
physical examination abnormality, or laboratory abnormality in which there is
reason to suspect that the patient has a disease or condition (e.g., having
seizures requiring treatment) that would be inappropriate for use of the study
drug, or that would affect interpretation of the study results or place the
patient at high risk, in the investigator's judgment.
17. Severe active or uncontrolled infection (≥CTCAE grade 2 infection), known human
immunodeficiency virus (HIV) infection; Known history of clinically significant
liver disease, including viral hepatitis [known hepatitis B virus (HBV)
carriers must exclude active HBV infection, i.e., HBV DNA positive (> 1×104
copies /mL or >2000 IU/ mL), known hepatitis C virus (HCV) infection with
positive HCV RNA (>1×103 copies /mL), or other hepatitis, cirrhosis.
18. Patients with any active, known or suspected autoimmune disease (including but
not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic
lupus erythematosus, rheumatoid arthritis, enteritis, multiple sclerosis,
vasculitis, glomerulonephritis, uveitis, hypophysitis, hyperthyroidism, etc.)
Patients with any active, known or suspected autoimmune disease (including but
not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic
lupus erythematosus, rheumatoid arthritis, enteritis, multiple sclerosis,
vasculitis, glomerulonephritis, uveitis, hypophysitis, hyperthyroidism, etc).
19. Known allergic reactions to other monoclonal antibodies or to any component of
surufatinib.
20. According to the investigator's judgment, patients have other factors that may
affect the results of the study or lead to the forced termination of the study,
such as alcohol abuse, drug abuse, other serious diseases (including mental
diseases) requiring combined treatment, family or social factors, etc., which
will affect the safety of patients.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Start date:
November 2023
Completion date:
June 2025
Lead sponsor:
Agency:
Wuhan Union Hospital, China
Agency class:
Other
Source:
Wuhan Union Hospital, China
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06134193
