2025-523630-59-00招募中2 期
Double-blind, randomized, placebo-controlled, study to evaluate the safety and efficacy of HRX215 in participants after major hepatectomy, preceded by two open pilot parts in participants after minor and after major hepatectomy due to colon carcinoma metastases
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 13
- 主要终点
- Incidence, severity, and relatedness of AEs/SAEs
研究概览
简要总结
- To assess the safety and tolerability of oral HRX215 in participants who had minor or major liver surgery due to CRLM
- To study how HRX215 is absorbed, modified, broken down, and removed from the body and compare these results between participants in this study and healthy individuals from earlier studies
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Participants aged 18 to 75 years (inclusive)
- •Written signed informed consent
- •Participants with liver metastases originating from a colon carcinoma planned for R0-intended hepatectomy for colorectal liver metastases. a. For pilot part 1 only: stable within 1-3 days after minor liver resection, otherwise normal nontumor liver parenchyma proven by histopathology assessment of a liver biopsy within 3 months before surgery
- •Participants with remnant liver volume (RLV) or estimated future liver remnant (FLR) after resection: a. For participants in pilot Part 1, after minor liver resection (RLV > 69%) by preoperative magnetic resonance imaging (MRI).b. For participants in pilot Part 2 and main study Part 3: participants with an estimated FLR of 30% - 50% (inclusive) prior to resection, calculated from preoperative CT or MRI after subtraction of tumor volume.
- •Preoperative assessment indicating that the participant is at low risk for PHLF (estimated <3–5%) based on surgeon’s standard practice and consistent with E-AHPBA-ESSO-ESSR Innsbruck Consensus guidelines for preoperative liver function assessment before hepatectomy
- •General health status World Health Organization (WHO) 0 or 1 or ECOG status 0 or 1
- •Estimated life expectancy > 6 months
- •Patients whose preoperative biological parameters are: a. Platelets ≥ 100,000/mm3, b. Polynuclear neutrophils ≥ 1000/mm3 c. Hemoglobin ≥ 9 g/dL (Posttransfusion patients can be included) d. Creatinine < 1.5 × upper limit of normal (ULN) e. Bilirubin ≤ ULN f. Albumin > LLN g. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ ULN h. INR ≤ 1.5
- •Must agree to use highly effective contraception specified in the Appendix A of the protocol from the time of informed consent until at least 36 days (5 half-lives + 30 days) after the last dose of study drug.
- •Participants must have adequate non-tumor liver tissue available for baseline histology for safety assessment purposes, either from planned resection or archival tissue collection within 3 months
排除标准
- •Liver cirrhosis
- •Contraindication to iodine contrast agents
- •Current treatment with anticoagulants (including DOACs, heparin,antivitamin K) that cannot be safety interrupted for at least 48 hrs before study treatment (Part 2 and 3).
- •Chemotherapy within the last 30 days preoperatively
- •More than 12 cycles or more than 6 months of preoperative chemotherapy
- •Anticipated need to start adjuvant chemotherapy prior to completion of 28 day treatment period including chemotherapy via intrahepatic arterial pump
- •Positive test at screening for active hepatitis B virus (HBV)/hepatitis C virus (HCV) or autoimmune hepatitis
- •Incomplete liver metastasis resection (recognized at time of surgery) (part 1).
- •Portal vein and/or hepatic vein embolization procedure (pilot part 2 and main study part) or surgical hepatic augmentation procedure e.g. ALPPS
- •Presence of high-grade dysplastic lesions which cannot be completely resected at the time of liver resection or a history of malignancy within the past five years prior to screening, except for subjects with completely resected basal cell carcinoma of the skin or carcinoma in situ of the cervix
- •Legal incapacity (persons in custody or under guardianship)
- •Preoperative presence of clinical ascites
- •Deprived of liberty Subject (by judicial or administrative decision)
- •Impossibility to sign the informed consent document or to adhere to the medical follow-up of the trial for geographical, social or psychological reasons
- •Contraindications against MRI or CT exams (according to local medical practice)
- •Inability to discontinue a concomitant medication which is primarily cleared by CYP2D6 from initiation of study treatment through day
- •Any other hepatobiliary cancer
- •Body mass index > 35 kg/m2
- •American Society of Anesthesiologists (ASA) Score ≥ 4
- •Peritoneal disease or findings indicating unresectability •Part 1: A Completeness of Cytoreduction (CC) Score greater than 0 identified: preoperatively or intraoperatively. Any preoperative or intraoperative findings indicating that curative resection is not achievable •Part 2 and main study part 3; Any preoperative radiologic finding consistent with peritoneal carcinomatosis. Any preoperative finding indicating that curative resection is not achievable
- •Ongoing participation or participation within the 28 days prior to inclusion in the study in another therapeutic trial with an experimental drug and during 6 month follow-up period post-hepatectomy.
- •Serious non-stabilized disease, active uncontrolled infection, or other serious underlying disorder likely to prevent the patient from receiving the treatment
- •Pregnancy (βHCG positive), breastfeeding
研究组 & 干预措施
White opaque capsules, size 1
Placebo
干预措施: White opaque capsules, size 1 (Drug)
HRX215
Test
干预措施: HRX215 (Drug)
结局指标
主要结局
Incidence, severity, and relatedness of AEs/SAEs
Incidence, severity, and relatedness of AEs/SAEs
Changes from baseline in vital signs and physical examination findings
Changes from baseline in vital signs and physical examination findings
Changes from baseline in clinical laboratory parameters (hematology,blood, glucose) at prespecified time points
Changes from baseline in clinical laboratory parameters (hematology,blood, glucose) at prespecified time points
Plasma PK of HRX215 (Cmax, Tmax, AUC etc.); comparison with Phase 1 healthy-subject PK data
Plasma PK of HRX215 (Cmax, Tmax, AUC etc.); comparison with Phase 1 healthy-subject PK data
次要结局
- Establishment of Efficacy (main study part 3): • Liver volume on POD1 and POD7 and increase in liver volume at POD7 vs. POD1 (absolute change from POD1 CT)
研究者
Chief Medical Officer
Scientific
HepaRegeniX GmbH
研究点 (13)
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