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Metastatic Colorectal CarcinomaPhase 2NCT07612007

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

A Phase 2 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Metastatic Colorectal Carcinoma and Metastatic Malignant Neoplasm in the Liver, run by Mayo Clinic at 1 site in United States.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 90 years
What is being tested?
Biopsy Procedure, Biospecimen Collection and Computed Tomography
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
80 participants
Where
1 siteUnited States
Study dates
1 Dec 2026to 1 Nov 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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
  • Other investigational agents
  • Radiation therapy
  • Major surgical procedures
  • REGISTRATION: Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • REGISTRATION: Uncontrolled intercurrent illness including, but not limited to:
  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • REGISTRATION: Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy
  • NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
  • REGISTRATION: Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm in the neoadjuvant setting or during active treatment phase of this study (adjuvant treatment after active treatment phase is completed does not apply)
  • REGISTRATION: Another active malignancy requiring therapy such as radiation, chemotherapy, or immunotherapy at time of study inclusion or within the past five years with the exception of basal cell carcinoma or carcinoma in situ of the cervix. Patients on hormonal therapy for treated breast or prostate cancer are permitted if they meet other eligibility criteria
  • REGISTRATION: History of myocardial infarction ≤ 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Clinical Trials Referral Office contact

855-776-0015

mayocliniccancerstudies@mayo.edu

Cancer Center Clinical Trials Referral Office contact

507-293-6386

United States1 site

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

    Clinical Trials Referral Office, 855-776-0015, mayocliniccancerstudies@mayo.edu

    Cancer Center Clinical Trials Referral Office, 507-293-6386

Other trials in United States

About this study

Official title: Phase 2B Study to Determine Efficacy of HRX215, a First Generation MKK4 Inhibitor Drug, in Improving Regeneration of the Remnant Liver After Portal Vein Embolization (PVE) of Colorectal Liver Metastasis (CRLM)

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.

Being tested
Biopsy Procedure, Biospecimen Collection, Computed Tomography, Darizmetinib, Embolization Therapy
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biopsy ProcedureProcedure or surgery

    Also called Biopsy, BIOPSY_TYPE, Bx

    Undergo tissue biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample collection

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT and CT-PET

  • DarizmetinibDrug

    Also called HRX 215, HRX-215, HRX215, LN 3348

    Given PO

  • Embolization TherapyDrug

    Also called Embolization, therapy, embolization

    Undergo PVE

  • HepatectomyProcedure or surgery

    Also called Liver Resection

    Undergo hepatectomy

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Placebo AdministrationDrug

    Given PO

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET (positron emission tomography), PET Scan, Positron emission tomography (procedure)

    Undergo CT-PET

Study groups in NCT07612007
Study groupRoleWhat they receive
Arm I (HRX215, PVE, hepatectomy)ExperimentalPatients undergo scheduled PVE on day 0. Starting 2 hours before undergoing PVE, patients receive HRX215 PO BID (orally twice daily) on days 0-27 in the absence of disease progression or unacceptable toxicity. Starting on or after day 32, patients may undergo scheduled hepatectomy. Patients also undergo blood sample collection, CT, MRI, and CT-PET throughout the study. Additionally, patients may undergo tissue biopsy during scheduled hepatectomy on study.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Darizmetinib; Drug: Embolization Therapy; Procedure: Hepatectomy; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography
Arm II (placebo, PVE, hepatectomy)Placebo comparatorPatients undergo scheduled PVE on day 0. Starting 2 hours before undergoing PVE, patients receive placebo PO BID (orally twice daily) on days 0-27 in the absence of disease progression or unacceptable toxicity. Starting on or after day 32, patients may undergo scheduled hepatectomy. Patients also undergo blood sample collection, CT, MRI, and CT-PET throughout the study. Additionally, patients may undergo tissue biopsy during scheduled hepatectomy on study.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Embolization Therapy; Procedure: Hepatectomy; Procedure: Magnetic Resonance Imaging; Drug: Placebo Administration; Procedure: Positron Emission Tomography

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Future liver remnant size (FLR)

    Will be defined as the percentage of the liver expected to remain after a planned hepatectomy. Will be compared between the two treatment groups [HRX215 versus (vs) placebo] utilizing an analysis of covariance (ANCOVA) F-test controlling for age, gender, and FLR at baseline.

    Measured: At day 28 post-baseline

Secondary outcomes (8)

  1. FLR size

    Will be defined as the percentage of the liver expected to remain after a planned hepatectomy. Will be compared between the two treatment groups (HRX215 vs placebo) utilizing an ANCOVA F-Test controlling for age, gender, and FLR at baseline.

    Measured: At day 7 post-baseline

  2. Incidence of adverse events (AEs)

    AEs will be graded using Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Each type of AE and grade will be recorded for each patient. The distribution of serious AEs as well as AEs of special interest will be compared between treatment arms descriptively to look for trends.

    Measured: Up to 28 days after last dose of study treatment

  3. Resectability after PVE

    The proportion of patients will be compared between treatment arms utilizing a Chi-Square test.

    Measured: At or after 28 days post-baseline

  4. Post-hepatectomy liver failure (PHLF)

    Will be defined according to the criteria issued by the International Study Group for Liver Surgery (ISGLS). Grading of PHLF into grades A to C will be performed, and grades B-C will be defined as severe PHLF. The proportion of patients will be compared between treatment arms utilizing a Chi-Square test.

    Measured: Between postoperative days 5 and 7

  5. Post-operative morbidity

    Will be defined according to the system issued in "Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey," a standardized, therapy-oriented system for grading postoperative surgical complications according to the treatment required to manage them rather than subjective severity. Complications range from Grade I, defined as any deviation from the normal postoperative course not requiring specific therapy, to Grade V, defined as death. Intermediate grades reflect increasing therapeutic intensity, from pharmacological treatment (Grade II), to interventions with or without general anesthesia (Grade III), and life-threatening complications requiring intensive care (Grade IV).. The proportion of patients will be compared between treatment arms utilizing a Chi-square test.

    Measured: Up to 360 days post-PVE

  6. Post-operative mortality

    Defined as patient death within the first 90 days after liver resection. The proportion of patients will be compared between treatment arms utilizing a Chi-Square test.

    Measured: Up to the first 90 days after liver resection

  7. Recurrence-free survival (RFS)

    Defined as the time from major liver resection to disease recurrence. Will be analyzed using the Kaplan-Meier Method. The distribution of RFS will be compared between treatment arms utilizing a two-sided log-rank test.

    Measured: From major liver resection to disease recurrence, assessed up to 360 days

  8. Overall survival (OS)

    Defined as the time from randomization to death from any cause. Will be analyzed using the Kaplan-Meier Method. The distribution of OS will be compared between treatment arms utilizing a two-sided log-rank test.

    Measured: From randomization to death from any cause, assessed up to 360 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 May 2026
  2. Study start1 Dec 2026 (estimated)
  3. Primary completion1 Nov 2028 (estimated)
  4. Study completion1 Nov 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
80 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07612007
Sponsor's protocol ID
MC250412
Other IDs
25-010359, R01DK140085
Status last verified
Oct 2026
First submitted
21 May 2026
Last updated
5 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Metastatic Colorectal Carcinoma and Metastatic Malignant Neoplasm in the Liver, run by Mayo Clinic at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 41 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Clinical Trials Referral Office (855-776-0015, mayocliniccancerstudies@mayo.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Future liver remnant size (FLR) (time frame: At day 28 post-baseline). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07612007.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2026.

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