DARIZMETINIB HYDROCHLORIDE for Colorectal liver metastases | Colon carcinoma metastases

Inclusion criteria

• {"criterion_text":"- Participants aged 18 to 75 years (inclusive)\n- Written signed informed consent\n- 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\n- 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.\n- 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\n- General health status World Health Organization (WHO) 0 or 1 or ECOG status 0 or 1\n- Estimated life expectancy > 6 months\n- 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\n- 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.\n- 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"}

Exclusion criteria

• {"criterion_text":"- Liver cirrhosis\n- Contraindication to iodine contrast agents\n- 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).\n- Chemotherapy within the last 30 days preoperatively\n- More than 12 cycles or more than 6 months of preoperative chemotherapy\n- Anticipated need to start adjuvant chemotherapy prior to completion of 28 day treatment period including chemotherapy via intrahepatic arterial pump\n- Positive test at screening for active hepatitis B virus (HBV)/hepatitis C virus (HCV) or autoimmune hepatitis\n- Incomplete liver metastasis resection (recognized at time of surgery) (part 1).\n- Portal vein and/or hepatic vein embolization procedure (pilot part 2 and main study part) or surgical hepatic augmentation procedure e.g. ALPPS\n- 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\n- Legal incapacity (persons in custody or under guardianship)\n- Preoperative presence of clinical ascites\n- Deprived of liberty Subject (by judicial or administrative decision)\n- Impossibility to sign the informed consent document or to adhere to the medical follow-up of the trial for geographical, social or psychological reasons\n- Contraindications against MRI or CT exams (according to local medical practice)\n- Inability to discontinue a concomitant medication which is primarily cleared by CYP2D6 from initiation of study treatment through day 28.\n- Any other hepatobiliary cancer\n- Body mass index > 35 kg/m2\n- American Society of Anesthesiologists (ASA) Score ≥ 4\n- 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\n- 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.\n- Serious non-stabilized disease, active uncontrolled infection, or other serious underlying disorder likely to prevent the patient from receiving the treatment\n- Pregnancy (βHCG positive), breastfeeding"}

Primary endpoints

• {"endpoint_text":"- Incidence, severity, and relatedness of AEs/SAEs\n- Changes from baseline in vital signs and physical examination findings\n- Changes from baseline in clinical laboratory parameters (hematology,blood, glucose) at prespecified time points\n- Plasma PK of HRX215 (Cmax, Tmax, AUC etc.); comparison with Phase 1 healthy-subject PK data","definition_or_measurement_approach":"- Incidence, severity and relatedness recorded for adverse events and serious adverse events as safety outcomes\n- Changes from baseline measured for vital signs and physical examination findings\n- Changes from baseline measured for clinical laboratory parameters (hematology, blood glucose) at prespecified time points\n- Plasma pharmacokinetics of HRX215 measured by standard PK parameters (Cmax, Tmax, AUC etc.) and compared with Phase 1 healthy-subject PK data"}

Secondary endpoints

• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Liver volume measured on postoperative day (POD) 1 and POD7 by CT; efficacy assessed as absolute change in liver volume at POD7 versus POD1 (change from POD1 CT)"}

France

Earliest CTIS Part Ii Submission Date

11-03-2026

Latest Decision Or Authorization Date

23-04-2026

Processing Time Days

43

Number Of Sites

3

Number Of Participants

10

Germany

Earliest CTIS Part Ii Submission Date

30-03-2026

Latest Decision Or Authorization Date

20-04-2026

Processing Time Days

21

Number Of Sites

6

Number Of Participants

19

Spain

Earliest CTIS Part Ii Submission Date

30-03-2026

Latest Decision Or Authorization Date

07-05-2026

Processing Time Days

38

Number Of Sites

4

Number Of Participants

11

Primary sponsor

Full Name

HepaRegeniX GmbH

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Contract research organisations

Name

Calian Contract Research Organisation Ltd.

Responsibilities

medical monitoring, CRO services

Third parties

• {"country":"United States","full_name":"Qstat","duties_or_roles":"Courier","organisation_type":"Industry"}
• {"country":"United Kingdom","full_name":"Greens","duties_or_roles":"Printing","organisation_type":"Industry"}
• {"country":"Germany","full_name":"spm²-safety projects & more GmbH","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scarritt Group Inc.","duties_or_roles":"Meeting Planners","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Radmd LLC","duties_or_roles":"Central imaging reading","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"Fortrea Germany GmbH","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Welocalize","duties_or_roles":"Translations","organisation_type":"Industry"}
• {"country":"United States","full_name":"Advarra","duties_or_roles":"Central Institutional Review Board","organisation_type":"Industry"}
• {"country":"France","full_name":"Pharmaspecific","duties_or_roles":"Patient reimbursement","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Calian Contract Research Organisation Ltd.","duties_or_roles":"medical monitoring, CRO services","organisation_type":"Industry"}
• {"country":"Canada","full_name":"Biotrial Bioanalytical Services Inc.","duties_or_roles":"PK analyses","organisation_type":"Pharmaceutical company"}