D-TACE-HAIC Combined With Envafolimab and Lenvatinib in the Treatment of Unresectable Intrahepatic Cholangiocarcinoma: a Prospective, Single-arm, Phase II Clinical Study

Recruiting

• Conditions: Intrahepatic Cholangiocarcinoma
• Interventions: Drug: TACE-HAIC, Envafolimab and Lenvatinib

• Registration Number: NCT06643208
• Lead Sponsor: Fujian Provincial Hospital

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-07-01
• Status Verified: 2024-10
• Study First Submitted: 2024-10-13
• Study First Submitted QC: 2024-10-13
• Last Update Submitted: 2024-10-13
• Study First Posted: 2024-10-16
• Last Update Posted: 2024-10-16
• Primary Completion: 2027-01-01
• Study Completion: 2027-03-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 37

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;

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Combination therapy group	TACE-HAIC, Envafolimab and Lenvatinib	Patients with unresectable cholangiocarcinoma were treated with D-TACE-HAIC (GEMOX regimen) combined with envafolimab and lenvatinib

Primary Outcome Measures

Name	Time	Method
Objective response rate, ORR	Four weeks after the initiation of medication	The Objective response rate (ORR) was defined as the complete response (CR) rate or the partial response (PR) rate according to RECIST v1.1 criteria.

Secondary Outcome Measures

Name	Time	Method
Treatment-related adverse events, TRAEs treatment-related adverse events	From the initiation of medication, with recordings made whenever an adverse reaction occurs, assessed up to 12 months	The incidence, spectrum and severity of adverse events (AE) and serious adverse events (SAE) were determined according to the NCI-CTCAE V5.0 standard. Dose suspension rate and dose termination rate due to adverse events.
Overall survival, OS	From date of enrollment until the date of death from any cause, assessed up to 60 months	The Overall survival (OS) was defined as the time between receiving treatment and observing death or loss of follow-up for any reason.
Progression-free survival, PFS	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	The Progression free survival (PFS) was defined as the time between the start of treatment and the progression of intrahepatic and/or extrahepatic tumors, or the occurrence of death or loss of follow-up for any reason.
Disease control rate, DCR	Four weeks after the initiation of medication	The Disease control rate (DCR) was defined as the complete response (CR) rate or the partial response (PR) rate or stable disease (SD) rate according to RECIST v1.1 criteria.

Trial Locations

Locations (1)

Fujian Provincial Hospital; 🇨🇳 Fuzhou, Fujian, China