A Clinical Trial Evaluating the Safety and Efficacy of Intravenous HNF4α srRNA in Treating Advanced ICC Patients
NCT Number: NCT06583993
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: EARLY_PHASE1
Conditions: Intrahepatic Cholangiocarcinoma
Interventions: DRUG: HNF4α srRNA
Sponsor: Shanghai Changzheng Hospital
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 9
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09
Completion Date: 2026-07

Summary:
The goal of this investigator-initiated, a single-arm, open-label, pilot study is to investigate the safety, tolerability, and efficacy of intravenous HNF4α srRNA treatment in subjects with advanced Intrahepatic Cholangiocarcinoma (ICC).

Condition of disease: advanced intrahepatic cholangiocarcinoma Intervention： HNF4α srRNA will be administered intravenously for the treatment of ICC. The dosing regimen is planned for a second dose 14 ± 3 days post-initial treatment, followed by subsequent treatments every 28 ± 7 days, with adjustments made based on patient tolerance and therapeutic response. This is a dose escalation assay employing a i3+3 design to assess escalating HNF4α srRNA dosages: 25 μg, 50 μg, and 100 μg. Post-initial dose, a 14-day dose-limiting toxicities (DLT) observation will evaluate tolerability and safety, guiding dose adjustments or selection of the Recommended Dose (RD) for the expansion phase. Cohorts may include up to 9 participants, adjusted for safety.

Drug: HNF4α srRNA, a drug specifically designed to target liver cancer cells and facilitate the expression of HNF4α.

Primary Outcome Measures: To evaluate the tolerability and safety for intravenous HNF4α srRNA in subjects with intrahepatic cholangiocarcinoma (ICC), Safety and tolerability are assessed based on the incidence of Dose-Limiting Toxicities (DLTs) within 14 days post-initial drug administration, along with the frequency and severity of adverse events (AEs), serious adverse events (SAEs), and events leading to treatment discontinuation throughout the treatment period, all evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0., Through study completion, an average of 2 years
Secondary Outcome Measures: To assess the objective response rate (ORR) by RECIST v1.1, To assess the proportion of subjects who have best overall response of complete response or partial response at the time of data cutoff based on RECIST v1.1., From the first study dose date until the date of documented complete response or partial response, assessed up to 24 months.|Duration of response based on RECIST v1.1, To assess the time from the first documentation of complete response or partial response to the date of first documentation of disease progression or death (whichever occurs first) based on RECIST v1.1, up to 24 months|Progression-free survival based on RECIST v1.1, To assess the time from the first study dose date to the date of first documentation of disease progression or death(whichever occurs first) based on RECIST v1.1, up to 24 months|Time to response based on RECIST v1.1, To assess the time from the date of first study dose to the date of first documentation of complete response or partial response based on RECIST v1.1, up to 24 months|Clinical benefit rate based on RECIST v1.1, To assess the proportion of subjects who have best overall response of complete response or partial response or durable stable disease (duration of stable disease ≥ 23 weeks) based on RECIST v1.1, up to 24 months|Overall Survival, To assess the time from the first study dose date until date of death from any cause . Subjects who are lost to follow-up and the subjects who are alive at the date of data cutoff will be censored at the date the subject was last known alive or the cut-off date, whichever comes earlier., Throughout the entire course of treatment until the end of the follow-up period, an average of 2 years|Patient Reported Outcome-1, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30，EORTC QLQ-C30, Through study completion, an average of 2 years|Patient Reported Outcome-2, the European Organization for Research and Treatment of Cancer Quality of Life, EORTC QLQ-BIL21 Questionnaire-BIL21, Through study completion, an average of 2 years|Patient Reported Outcome-3, The Generic Euroquol Five Dimension Five Level (EQ-5D-5L) Questionnaire, Through study completion, an average of 2 years|The impact of HNF4α srRNA treatment on tumor biomarkers in serum, The changes in tumor markers after treatment, including CA19-9, carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP), Through study completion, an average of 2 years
Other Outcome Measures: The assessment of whether the efficacy of HNF4α srRNA is related to specific mutations, Identification of whether the efficacy of HNF4α srRNA is related to specific gene mutations in ICC tissue through next-generation sequencing, Through study completion, an average of 2 years|The impact of HNF4α srRNA treatment on proteomics in serum, The detection of proteomics in patient serum before and after treatment of HNF4α srRNA, Through study completion, an average of 2 years|The impact of HNF4α srRNA treatment on metabolomics in serum, The detection of metabolomics in patient serum before and after treatment of HNF4α srRNA, Through study completion, an average of 2 years|The impact of HNF4α srRNA treatment on cytokines in serum, The detection of cytokines in patient serum before and after treatment of HNF4α srRNA, Through study completion, an average of 2 years|The impact of HNF4α srRNA treatment on immune cell subsets in serum or tissuses, The detection of immune cell subsets in patient serum or ICC tissues before and after treatment of HNF4α srRNA, Through study completion, an average of 2 years|The impact of HNF4α srRNA treatment on the quantitative enhancement volume standards of intrahepatic cholangiocarcinoma, The changes in tumor enhancement volume pre- and post-treatment, Through study completion, an average of 2 years