A Phase 2, Open-label, Single Arm Study of Combined Drug-eluting Beads-TACE, Lenvatinib and Pucotenlimab as Conversion Therapy for Unresectable Intrahepatic Cholangiocarcinoma
Overview
- Phase
- Phase 2
- Intervention
- DEB-TACE
- Conditions
- Cholangiocarcinoma Non-resectable
- Sponsor
- Tongji Hospital
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- Number of Patients Amendable to Curative Surgical Interventions
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is an open-label, single-arm, phase 2 study. The purpose of study is to evaluate the feasibility and safety of drug eluting beads-transcatheter arterial chemoembolization combined with lenvatinib and pucotenlimab as conversion therapy for unresectable intrahepatic cholangiocarcinoma.
Detailed Description
Pucotenlimab is a new humanized PD-1-specific monoclonal antibody. On September 29, 2022, the National Medical Products Administration of China approved the marketing application of Pucotenlimab Injection for the treatment of patients with microsatellite highly unstable (MSI-H)/mismatch repair function defective (dMMR) solid tumors who have failed prior first-line and above systemic therapy. There have been studies and reports on systemic chemotherapy with GEMOX regimen combined with lenvatinib and PD-1 monoclonal antibody for the treatment of intrahepatic cholangiocarcinoma. Currently, a multicenter, phase 2 study evaluating the efficacy of pucotenlimab in patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumors is underway. The objective response rate (ORR) is 49.0% (95% CI 38.86%-59.20%), while the median progression-free survival and overall survival have not been reached. Grade ≥3 treatment-related adverse events were observed in 18 of 100 patients. The efficacy of this antibody in patients is promising. Based on the results of these previous studies, this study intends to evaluate the efficacy and safety of drug eluting beads-transcatheter arterial chemoembolization (GEMOX regimen) combined with lenvatinib and pucotenlimab in the down-stage conversion treatment of patients with unresectable intrahepatic cholangiocarcinoma.
Investigators
Ze-yang Ding, MD
Prof.
Tongji Hospital
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed intrahepatic cholangiocarcinoma.
- •Age ≥18 years.
- •ECOG performance status score of 0 or
- •Not suitable for radical surgery (including radical hepatic resection, liver transplantation or ablation) after evaluation by the MDT expert group of treating hepatobiliary cancer. Specifically, any of the following conditions are met：
- •R0 resection is not feasible.
- •in subjects without cirrhosis, the volume of normal liver parenchyma is less than 30% of the total volume, or in patients with cirrhosis, the volume of normal liver parenchyma is less than 40% of the total volume, or ICG-R15\>15%.
- •Number of lesions \>
- •No prior systemic anti-tumor treatment for intrahepatic cholangiocarcinoma before the first dose.
- •According to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1), at least 1 measurable lesion, or a measurable lesion that has clearly progressed (based on RECIST V1.1 criteria) after local treatment.
- •Subjects with portal vein tumor thrombus (PVTT):
Exclusion Criteria
- •Histologically/cytologically confirmed sarcomatoid intrahepatic cholangiocarcinoma, mixed hepatocellular carcinoma, etc.
- •History of hepatic encephalopathy or liver transplantation.
- •Clinically symptomatic pleural effusion, ascites, or pericardial effusion requiring drainage. Patients with only radiologically detected minimal pleural effusion, ascites, or pericardial effusion without symptoms can be included.
- •Acute or chronic active hepatitis B or C infection, with hepatitis B virus (HBV) DNA \>2000IU/ml or 10\^4 copies/ml; hepatitis C virus (HCV) RNA \>10\^3 copies/ml; co-positive for hepatitis B surface antigen (HbsAg) and anti-HCV antibody. Patients who meet the above criteria after antiviral treatment with nucleoside analogs can be included.
- •Presence of central nervous system metastases.
- •History of esophageal or gastric variceal bleeding due to portal hypertension within the past 6 months. Patients assessed by the investigator to be at high risk of bleeding.
- •Any life-threatening bleeding event within the past 3 months, including those requiring blood transfusion, surgery or local treatment, or continuous drug treatment.
- •History of arterial or venous thromboembolic events within the past 6 months, including myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or any other serious thromboembolic events. Exceptions are made for thrombosis formation related to implanted venous infusion ports or catheters, or superficial vein thrombosis that has stabilized after routine anticoagulation treatment. Preventive use of low-dose low molecular weight heparin (such as enoxaparin 40 mg/day) is allowed.
- •Continuous use of aspirin (\>325 mg/day) or other known platelet function inhibitors such as clopidogrel or ticlopidine for 10 days within 2 weeks prior to the first dose.
- •Uncontrolled hypertension, with systolic blood pressure ≥150mmHg or diastolic blood pressure ≥100mmHg after optimal medical treatment, history of hypertensive crisis or hypertensive encephalopathy.
Arms & Interventions
DEB-TACE-len-puco
Patients with advanced intrahepatic cholangiocarcinoma who was initially evaluated unsuitable for the radical therapy and received combined DEB-TACE plus lenvatinib (Len) and pucotenlimab as conversion therapy for downstaging.
Intervention: DEB-TACE
DEB-TACE-len-puco
Patients with advanced intrahepatic cholangiocarcinoma who was initially evaluated unsuitable for the radical therapy and received combined DEB-TACE plus lenvatinib (Len) and pucotenlimab as conversion therapy for downstaging.
Intervention: Lenvatinib plus pucotenlimab
Outcomes
Primary Outcomes
Number of Patients Amendable to Curative Surgical Interventions
Time Frame: from the date of first treatment to the date of last treatment, an average of 3 years
Number of patients amendable to curative surgical interventions defined as number of patients receiving curative surgical resection, transplantation, or ablation after successful down-sizing of tumor(s) by intervention.
Secondary Outcomes
- Overall survival (OS)(from the date of first treatment to the date of death from any cause, assessed up to 5 years)
- Time to progression (TTP)(from the date of first treatment to radiographically documented progression according to mRECIST, assessed up to 3 years)
- Time to intrahepatic tumor progression (TTITP)(from the date of first treatment to radiographically documented intrahepatic tumor progression according to mRECIST, assessed up to 3 years)
- Incidence of Study-Related Adverse Events(from the date of first treatment to 90 days after last treatment, around 3 years and 90 days)
- Pathological complete response (pCR)(from the date of first study treatment to radiographically documented progression according to mRECIST 1.1 or death from any cause, whichever occurs first, assessed up to 5 years)
- Disease control rate (DCR)(from the date of first treatment to radiographically documented response according to mRECIST, assessed up to 3 years)
- Duration of response (DoR)(from the date of first documented evidence of CR or PR to first documented sign of PD or death from any cause according to mRECIST 1.1, assessed up to 3 years)
- overall response rate (ORR) measured by mRECIST criteria(from the date of first treatment to radiographically documented progression according to mRECIST, assessed up to 3 years)
- Progression-free survival (PFS)(from the date of first treatment to radiographically documented progression according to mRECIST 1.1 or death from any cause, whichever occurs first, assessed up to 3 years)
- Quality of Life (QoL) after treatment(assessed form the date of first followup to radiographically documented progression or or death from any cause, up to 3 years)