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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
36
transcatheter arterial chemoembolization with doxorubicin embedded eluting beads- was performed every 3 weeks through the tumor feeding arteries.
lenvatinib (8mg, qd) plus pucotenlimab (200mg, q3w)
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, China
RECRUITINGNumber of Patients Amendable to Curative Surgical Interventions
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.
Time frame: from the date of first treatment to the date of last treatment, an average of 3 years
overall response rate (ORR) measured by mRECIST criteria
Complete response (CR): Disappearance of any intra-tumoral arterial enhancement in all target lesions; Partial response (PR): At least a 30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions; Stable disease (SD): Any cases that do not qualify for either partial response or progressive disease; Progressive disease (PD): An increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since treatment started.
Time frame: from the date of first treatment to radiographically documented progression according to mRECIST, assessed up to 3 years
Overall survival (OS)
measured from date of first treatment to the date of death from any cause. Participants alive or lost to follow-up will be censored at the date of their last visit.
Time frame: from the date of first treatment to the date of death from any cause, assessed up to 5 years
Progression-free survival (PFS)
measured from the date of first treatment to radiographically documented progression according to mRECIST 1.1 or death from any cause (whichever occurs first). Participants alive and without disease progression or lost to follow-up will be censored at the date of their last radiographic assessment.
Time frame: 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
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Time to progression (TTP)
Time to progression (TTP): measured from the date of first treatment to radiographically documented progression according to mRECIST 1.1. This does not include death from any cause.
Time frame: from the date of first treatment to radiographically documented progression according to mRECIST, assessed up to 3 years
Time to intrahepatic tumor progression (TTITP)
Time to intrahepatic tumor progression (TTITP): measured from the date of first treatment to radiographically documented intrahepatic tumor progression according to mRECIST 1.1. This does not include death from any cause.
Time frame: 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
Incidence, nature, and severity of adverse events graded according to the United States National Cancer Institute The Common Terminology Criteria for Adverse Events (NCI-CTCAE 5.0)
Time frame: from the date of first treatment to 90 days after last treatment, around 3 years and 90 days
Pathological complete response (pCR)
Pathological response is assessed as the percentage of surface with non-viable cancer cells (represented by necrosis or fibrosis, the ultimate stage of necrosis) in relation to the total tumor area and will be equal to: 100% - viable cancer cells (%). If there are multiple tumors, the mean percentage will be used.
Time frame: 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)
Disease control rate (DCR): percentage of patients with CR, PR, or stable disease (SD) ≥6 months based on mRECIST
Time frame: from the date of first treatment to radiographically documented response according to mRECIST, assessed up to 3 years
Duration of response (DoR)
Defined as the time from first documented evidence of CR or PR until the first documented sign of disease progression (PD) or death from any cause
Time frame: 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
Quality of Life (QoL) after treatment
The life quality of every subject is assessed every 3 months during follow up according to the 45-item FACT-Hep questionnaire, which assesses generic HRQL concerns and disease-specific issues.
Time frame: assessed form the date of first followup to radiographically documented progression or or death from any cause, up to 3 years