CCR5 Targeting Leronlimab in Combination With Hepatic Arterial Infusion Floxuridine and Systemic Therapy for the Treatment of Colorectal Cancer Liver Metastases, CHAMP Trial
Intrahepatic Infusion Procedure: Given floxuridine via HAI pump
Leronlimab: Given SC
Magnetic Resonance Imaging: Undergo MRI
Surgical Procedure: Undergo surgical resection with HAI pump placement
Systemic Therapy: Given SOC systemic therapy
Study summary
This phase I/Ib trial tests the effect of leronlimab in combination with hepatic arterial infusion (HAI) floxuridine (FUDR)and standard of care (SOC) systemic therapy in treating patients with colorectal cancer that has spread from where it first started to the liver (metastatic). Leronlimab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets, such as CCR5 which is expressed on T cells (a type of immune cell), which may cause the body to make an immune response (antigens) and may also improve the effectiveness of treatment. HAI delivers chemotherapy, such as floxuridine, directly to the liver. Catheters are put into an artery in the groin that leads directly to the liver and drugs are given through the catheters. Floxuridine is in a class of medications called antimetabolites. It works by slowing or stopping the growth of tumor cells in your body. HAI can deliver floxuridine at up to 300 times the concentrations that can be given through the vein. Systemic therapy is treatment using substances that travel through the bloodstream, reaching and affecting cells all over the body. Giving leronlimab in combination with HAI floxuridine and SOC systemic therapy may be safe, tolerable, and/or safe in treating colorectal cancer patients with liver metastases.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Documented informed consent of the participant and/or legally authorized representative
* Agreement to allow the use of archival tissue from diagnostic tumor and/or surgical biopsies
* If unavailable, exceptions may be granted with study principal investigator (PI) approval
* Age: ≥ 18 years
* Eastern Cooperative Oncology Group (ECOG) ≤ 2
* Confirmed metastatic colorectal cancer with liver dominant metastases amenable and a candidate for adjuvant HAI floxuridine (FUDR) pump therapy as determined by the clinical team.
* Note: patients should be candidates for an R0/R1 complete resection of the liver metastases with the goal of ideally achievement of no evidence of disease (NED) or treated disease
* Note: peri/intra-operative interventional ablation therapy, radiation therapy, as well as liver-directed therapy to achieve NED/treated disease is allowed. Patients who are getting a liver pump only and no surgery due to unresectable liver metastases are not eligible for this study
* Hemoglobin ≥ 8 g/dL (within 14 days prior to day 1 of protocol therapy)
* NOTE: Iron replacement and/or red blood cell transfusions are permitted as long as the patient is not actively bleeding
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (unless has Gilbert's syndrome) (within 14 days prior to day 1 of protocol therapy)
* NOTE: If the patient has Gilbert's disease, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be ≤ 3.0 x ULN
* AST ≤ 5.0 x ULN (within 14 days prior to day 1 of protocol therapy)
* ALT ≤ 5.0 x ULN (within 14 days prior to day 1 of protocol therapy)
* Creatinine ≤ 1.5 x institutional ULN (within 14 days prior to day 1 of protocol therapy) OR
* Creatinine clearance ≥ 50 mL/min calculated by the Cockcroft-Gault method
* Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (within 14 days prior to day 1 of protocol therapy)
* If the urine test is positive or cannot be confirmed as negative, a qualitative or quantitative serum pregnancy test will be required
* Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least three months after the last dose of protocol therapy
* Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)
Exclusion Criteria:
* Concurrent participation in another interventional study. Participation in observational clinical studies is permitted
* Chemotherapy, biological therapy, immunotherapy within 14 days or five half-lives (whichever is shorter for non-radiation therapy) prior to day 1 of protocol therapy
* Note: Radiation therapy and/or other peri/intra-operative other liver directed therapy is allowed; patients need to have sufficiently recovered from it as assessed by the treating physician or site PI
* Patients using herbal medications or supplements. These also need to be stopped 14 days prior to day 1 of protocol therapy. Exceptions are over-the-counter medications or supplements taken for supportive care (e.g., vitamins, ginseng or electrolytes for fatigue) are permitted. Participants will be advised to discuss with the study team prior to initiating any new medication or supplement during the study
* Significant comorbidities or conditions that would impede candidacy for surgery or trial participation
* Known hypersensitivity to leronlimab or components of the formulation
* Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
Primary outcome measure(s)
Proportion of patients completing all four planned hepatic arterial infusion (HAI) cycles with a relative dose intensity ≥ 80% for HIA floxuridine (FUDR) — Up to 4 cycles (cycle length = 28 days) Will be calculated using the number of patients who complete all four planned HAI cycles with a relative dose intensity ≥ 80% for HAI FUDR divided by the total number of enrolled patients.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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