Combination Therapy of HAIC, Surufatinib and Tislelizumab for Unresectable or Metastatic Biliary Tract Cancer

Launched by WUHAN UNION HOSPITAL, CHINA · Nov 12, 2023

Keywords

ClinConnect Summary

This clinical trial is exploring a new treatment approach for patients with biliary tract cancer that cannot be surgically removed or has spread to other parts of the body. Specifically, the study is looking at a combination therapy involving HAIC (a type of local chemotherapy), surufatinib (a medication that stops blood vessels from helping tumors grow), and tislelizumab (an immunotherapy that helps the body’s immune system fight cancer). The goal is to see how effective and safe this combination is for patients who have not yet received treatment for their condition.

To be eligible for this trial, participants need to be between 18 and 75 years old, have a confirmed diagnosis of unresectable or metastatic intrahepatic cholangiocarcinoma or gallbladder cancer, and have a good performance status (meaning they can carry out daily activities with little to no trouble). They should also have certain health criteria met, such as stable organ functions. Participants will receive the new treatment and will be monitored closely for any side effects or changes in their condition. It's important to note that this trial is not yet recruiting patients, so those interested will need to wait until it officially starts.

Gender

ALL

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.