HRX215, A First Generation MKK4 Inhibitor Drug, for the Treatment of Patients With Colorectal Liver Metastasis After Undergoing a Portal Vein Embolization

Starting soon · Phase 2 · Has a placebo group

Conditions studied: Metastatic Colorectal Carcinoma, Metastatic Malignant Neoplasm in the Liver, Resectable Colorectal Carcinoma, Stage IV Colorectal Cancer AJCC v8

In brief

This phase IIb trial tests the effect of HRX215 in treating patients with colorectal cancer that has spread from where it first started to the liver (liver metastasis) after undergoing a portal vein embolization (PVE). Currently, surgery to remove the tumor (hepatectomy) remains the only potential treatment for cure. However, less than 30% of patients are considered resectable (can be removed by surgery) at the time of diagnosis. The risk of liver failure and other complications rise with larger areas liver that is removed during surgery. Therefore, the potential for surgery is determined by the amount of liver that will remain after resection. PVE is a standard strategy to increase the potential for resection. A PVE is a procedure that blocks the portal vein (a blood vessel that carries blood to the liver) to prevent flow of blood to the tumor. HRX215 targets and binds to MKK4, a protein found on liver cells plays a part in cellular growth and prevents liver repair and regrowth of cells and tissue. Blocking the activity of MKK4 may help prevent liver failure, protect liver cells and improve liver mass. Giving HRX215 after a PVE may help improve the rate of liver regrowth and increase the likelihood of hepatectomy in patients with colorectal liver metastasis.

Key facts

Study ID

NCT07612007

Run by

Mayo Clinic

People needed

80

Starts

2026-09-01

Expected to finish

2028-08-01

Last updated by the study team

2026-06-12

Who can join

Age: 18 and older, up to 90. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• REGISTRATION: Adults 18-90 years
• REGISTRATION: Individuals with metachronous colorectal carcinoma liver metastases (CRCLM) after resection of the primary OR synchronous CRCLM with planned simultaneous resection of primary and metastatic disease
• REGISTRATION: Measurable intrahepatic disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) and considered resectable by multidisciplinary tumor board with at least one senior hepatic surgeon
• REGISTRATION: Available CT suitable for volumetric studies on FLR ≤ 21 days
• REGISTRATION: Clinical indication for PVE prior to major hepatectomy as evaluated by at least one senior hepatic surgeon
• REGISTRATION: Estimated life expectancy ≥ 3 months as evaluated and approximated by a senior hepatic surgeon
• REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
• REGISTRATION: Platelets ≥ 100,000/mm\^3 (≤ 15 days prior to registration)
• REGISTRATION: Polynuclear neutrophils ≥ 1000/mm\^3 (≤ 15 days prior to registration)
• REGISTRATION: Hemoglobin ≥ 9 g/dL (≤ 15 days prior to registration) (post-transfusion participants can be included)
• REGISTRATION: Creatinine ≤ 1.5 x upper limit of normal (ULN) (≤ 15 days prior to registration)
• REGISTRATION: Bilirubin ≤ ULN (≤ 15 days prior to registration)
• REGISTRATION: Albumin ≥ 3 g/dL (≤ 15 days prior to registration)
• REGISTRATION: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN (≤ 15 days prior to registration)
• REGISTRATION: International normalized ratio ≤ 1.5 (≤ 15 days prior to registration)
• REGISTRATION: Of note, a slight deviation from normal ranges of liver function tests, circulating cell counts, and kidney function can be assumed after systemic neoadjuvant chemotherapy prior to PVE (Field et al., 2008; Takamoto et al., 2010; Lock et al., 2017), which is accounted for in the above list. These parameters at inclusion will then serve as patient baseline
• REGISTRATION: Negative pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only. Serum or urine human chorionic gonadotropin test is suitable. Can be done with a home test and results reported by participant to the site
• REGISTRATION: Provide written informed consent
• REGISTRATION: Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
• RANDOMIZATION: Adults 18-90 years
• RANDOMIZATION: Individuals with metachronous CRCLM after resection of the primary OR synchronous CRCLM with planned simultaneous resection of primary and metastatic disease
• RANDOMIZATION: Estimated life expectancy ≥ 3 months as evaluated and approximated by a senior hepatic surgeon
• RANDOMIZATION: Measurable intrahepatic disease as defined by RECIST and considered resectable by multidisciplinary tumor board with at least one senior hepatic surgeon
• RANDOMIZATION: Available CT suitable for volumetric studies on FLR ≤ 21 days
• RANDOMIZATION: Scheduled for PVE prior to major hepatectomy

You may not qualify if…

• REGISTRATION: Cirrhosis or clinical ascites
• REGISTRATION: Patients with synchronous CRCLM and scheduled staged approach (i.e., resection of metastatic hepatic disease after PVE followed by resection of the colorectal primary in a second operation)
• REGISTRATION: Any liver cancer other than CRLM
• REGISTRATION: Contraindications to imaging or perioperative management:
• Allergy/contraindication to iodine contrast
• Anticoagulation with heparin/antivitamin K (AVK) that cannot be interrupted for 48 hours
• Antiplatelet therapy (e.g., clopidogrel) that cannot be interrupted for 5 days
• REGISTRATION: Inability to discontinue cytochrome P450 (CYP)2D6 inhibitor concomitant medication from start of trial treatment to day 28
• REGISTRATION: Inoperability due to underlying chronic diseases and co-morbidities as assessed by the hepatobiliary surgeon during screening visit
• REGISTRATION: Anticipated need to start adjuvant chemotherapy prior to completion of 28 day treatment period
• REGISTRATION: Positive test at screening for active hepatitis B virus (HBV)/hepatitis C virus (HCV), defined as history of seropositivity for hepatitis B virus (unless immune due to vaccination or resolved natural infection or unless passive immunization due to immunoglobulin therapy), i.e., positive test for anti-hepatitis B core antigen and negative test for anti-hepatitis B surface antibody. Ongoing, non-cured hepatitis C virus (HCV) infection. Likewise, autoimmune hepatitis will be excluded based on serological [antinuclear antibodies (ANA), smooth muscle antibodies (SMA), and biochemical parameters AST and ALT], patients with serological and/or biochemical findings suggestive of probable autoimmune hepatitis will be excluded
• REGISTRATION: Legal incapacity (persons in custody or under guardianship)
• REGISTRATION: Deprived of liberty subject (by judicial or administrative decision)
• REGISTRATION: Impossibility to sign the informed consent document or to adhere to the medical follow-up of the trial for geographical, social, or psychological reasons
• REGISTRATION: Any of the following because this study involves an investigational agent, the genotoxic, mutagenic and teratogenic effects of which on the developing fetus and newborn are unknown
• Pregnant persons
• Nursing persons
• Persons of childbearing potential who are unwilling to employ adequate contraception. Participants of childbearing potential must use highly effective contraception (hormonal methods, intrauterine device (IUD)/intrauterine system (IUS), bilateral tubal occlusion, or vasectomized partner) during treatment and for a defined post-treatment period of 30 days. True abstinence is acceptable if consistent with lifestyle. Barrier methods alone are insufficient unless combined. Male participants with partners of childbearing potential must use condoms and avoid sperm donation during and after treatment
• REGISTRATION: Any of the following prior therapies:
• Major surgical procedures ≤ 3 weeks prior to registration
• Bevacizumab as part of systemic cancer treatment ≤ 2 weeks prior to registration
• REGISTRATION: Failure to recover from any adverse events related to any of the following therapies received prior to registration:
• Chemotherapy
• Immunotherapy
• Targeted therapies

Where it is running

• Mayo Clinic in Rochester — Rochester, Minnesota, United States

Full record on ClinicalTrials.gov

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