D-TACE-HAIC Combined With Envafolimab and Lenvatinib for Unresectable ICC

Official title

Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital

Overview

This is a prospective, single-arm, multicenter, phase II trial to evaluate the efficacy and safety of D-TACE-HAIC (GEMOX protocol) in combination with Envafolimab and Lenvatinib for unresectable intrahepatic cholangiocarcinoma.

Interventions

• Drug TACE-HAIC, Envafolimab and Lenvatinib
  TACE-HAIC (GEMOX regimen) combined with Envafolimab and Lenvatinib

Primary outcome measures

• Objective response rate, ORR [Time frame: Four weeks after the initiation of medication]

Secondary outcome measures (4)

• Overall survival, OS [Time frame: From date of enrollment until the date of death from any cause, assessed up to 60 months]
• Progression-free survival, PFS [Time frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months]
• Disease control rate, DCR [Time frame: Four weeks after the initiation of medication]
• Treatment-related adverse events, TRAEs treatment-related adverse events [Time frame: From the initiation of medication, with recordings made whenever an adverse reaction occurs, assessed up to 12 months]

Eligibility criteria

Inclusion criteria

• 1\. Ages of 18 and 75;
• 2\. Child-Pugh liver function grade: A/B;
• 3\. ECOG score (see annex for scoring standards) : ≤1 score;
• 4\. ICC was confirmed by pathology and evaluated by two senior hepatobiliary surgeons as unresectable for surgery (including multiple intrahepatic lesions, local vascular invasion, local lymph node metastasis, and distant metastasis);
• 5\. According to RECIST 1.1 criteria, the patient has at least one measurable lesion (the CT/MRI scan diameter of the lesion can be measured ≥10mm, and the lesion has not received local treatment such as radiotherapy or freezing);
• 6\. The expected survival time is greater than 3 months;
• 7\. Patients who had not received any tumor-related targeting, immunization, radiotherapy or chemotherapy before enrollment;
• 8\. Functional indexes of vital organs met the following requirements: · Routine blood: absolute neutrophil count ≥1.5×109/L, Hb≥9.0g/L, PLT≥75×109/L; · Liver function: total bilirubin ≤1.5 times the upper limit of normal (ULN) (≤2.5 times ULN after biliary drainage in patients with obstructive jaundice); Alanine aminotransferase (ALT), aspartate aminotransferase (AST)≤ 5x ULN, albumin ≥30g /L; · Renal function: serum creatinine ≤1.5mg/dL, creatinine clearance ≥60ml /min; · Coagulation function: International standardized ratio (INR) and activated partial thromboplastin time (APTT)≤1.5 times ULN;
• 9\. No history of severe arrhythmia or heart failure; No history of severe ventilation dysfunction or severe pulmonary infection;
• 10\. Women of childbearing age should agree to use contraception during the use of medication and for 6 months after the end of medication; Patients who had a negative serum or urine pregnancy test in the 7 days prior to study enrollment and must be non-lactating patients, men should consent to use contraception during the study period and for 6 months after the end of the study period.

Exclusion criteria

• 1\. Patients who have previously received other local anti-tumor treatments (such as radiotherapy, radiofrequency ablation, etc.), who are allowed to relapse 6 months after previous surgery, and who are allowed to undergo biliary drainage (including PTCD and biliary stent implantation);
• 2\. History of allergy to gemcitabine, oxaliplatin, Envolizumab, Renvastinib and its components;
• 3\. A history of other malignant tumors within the past 5 years or at the same time, except cured basal cell carcinoma of the skin, cervical carcinoma in situ and thyroid papillary carcinoma;
• 4\. Patients who have previously received an organ transplant or are planning to receive an organ transplant;
• 5\. The presence of any active autoimmune disease or patients with autoimmune disease and expected recurrence (such as interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases and syndromes);
• 6\. History of immune deficiency; The patient is taking immunosuppressants or systemic hormone therapy for immunosuppressive purposes and continues to use it within 2 weeks prior to signing the informed consent;
• 7\. Known hereditary or acquired bleeding (e.g. coagulation disorders) or thrombotic tendencies, e.g. in hemophiliacs; Is currently or recently (within 10 days prior to the start of study therapy) used full dose oral or injectable anticoagulants or thrombolytic agents for therapeutic purposes (prophylactic use of low-dose aspirin, low-molecular weight heparin permitted);
• 8\. Serious infections, such as severe pneumonia, bacteremia, and comorbiditis requiring hospitalization, occurred within 4 weeks prior to the first use of the study drug; Baseline chest imaging findings indicate active lung inflammation, signs and symptoms of infection within 2 weeks prior to the first use of the study drug, or the need for oral or intravenous antibiotic treatment (excluding prophylactic antibiotic use);
• 9\. Patients with mental illness; Have a history of psychotropic substance abuse, alcoholism and drug use;
• 10\. Pregnant or lactating women;
• 11\. Those who, according to the judgment of the researcher, should not participate in this experiment for other reasons;

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Cohort

Study locations

China · 1 center

• Fujian Provincial Hospital — Fuzhou

Identifiers

NCT: NCT06643208 · TALENP005

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗