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

Exclusion Criteria

• •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
• •* 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