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

ConditionsMetastatic Colorectal CarcinomaMetastatic Malignant Neoplasm in the LiverResectable Colorectal CarcinomaStage IV Colorectal Cancer AJCC v8
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-90
SponsorMayo Clinic

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Allergy/contraindication to iodine contrast

Trial design

Design model

Parallel

Treatments tested in this trial

  • Biopsy Procedure

    Procedure/Surgery

    Undergo tissue biopsy

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Computed Tomography

    Procedure/Surgery

    Undergo CT and CT-PET

  • Darizmetinib

    Drug

    Given PO

  • Embolization Therapy

    Drug

    Undergo PVE

  • Hepatectomy

    Procedure/Surgery

    Undergo hepatectomy

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Placebo Administration

    Drug

    Given PO

  • Positron Emission Tomography

    Procedure/Surgery

    Undergo CT-PET

Treatment groups

80 Participants
are divided into 2 treatment groups
Group A: Arm I (HRX215, PVE, hepatectomy)Experimental treatment 8 interventions
Group B: Arm II (placebo, PVE, hepatectomy)Placebo comparator 8 interventions

Trial outcomes

Primary outcomes

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.

Time frame
At day 28 post-baseline

Secondary outcomes

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.

Time frame
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.

Time frame
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.

Time frame
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.

Time frame
Between postoperative days 5 and 7

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Mayo Clinic

Lead sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: