A Phase 1/1b Single Arm Safety Lead in Study of Leronlimab (CCR5 Blockade) With Hepatic Arterial Infusion Pump Therapy Delivering Floxuridine (FUDR) and Concurrent Systemic Therapy in Colorectal Cancer Liver Metastases Patients (CHAMP)
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 36
- 试验地点
- 3
- 主要终点
- Proportion of patients completing all four planned hepatic arterial infusion (HAI) cycles with a relative dose intensity ≥ 80% for HIA floxuridine (FUDR)
研究概览
简要总结
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.
详细描述
PRIMARY OBJECTIVE:
I. To evaluate the feasibility of administering four planned cycles of combined standard-of-care systemic therapy, hepatic arterial infusion (HAI) floxuridine (FUDR), and leronlimab as reflected by relative dose intensity in the study population.
SECONDARY OBJECTIVES:
I. To characterize the safety profile of the combined regimen. II. To evaluate the anti-tumor activity of leronlimab administered subcutaneously alongside HAI pump and systemic therapy in patients with colorectal cancer with liver metastases, as assessed by 1 year and 2 year progression-free survival (PFS) and median progression free-survival.
III. To evaluate liver-specific disease control with leronlimab plus HAI pump and systemic therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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)
研究组 & 干预措施
Treatment (leronlimab, HAI FUDR, systemic therapy)
Patients receive leronlimab SC weekly with SOC systemic therapy for up to 6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection with HAI pump placement. Starting 4 weeks after surgery, patients receive floxuridine continuously via HAI pump every 14 days of each cycle and resume leronlimab SC weekly in combination with SOC systemic therapy of each cycle. Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and CT and/or MRI throughout the study. Additionally, patients may optionally undergo biopsy on study.
干预措施: Biopsy Procedure (Procedure)
Treatment (leronlimab, HAI FUDR, systemic therapy)
Patients receive leronlimab SC weekly with SOC systemic therapy for up to 6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection with HAI pump placement. Starting 4 weeks after surgery, patients receive floxuridine continuously via HAI pump every 14 days of each cycle and resume leronlimab SC weekly in combination with SOC systemic therapy of each cycle. Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and CT and/or MRI throughout the study. Additionally, patients may optionally undergo biopsy on study.
干预措施: Biospecimen Collection (Procedure)
Treatment (leronlimab, HAI FUDR, systemic therapy)
Patients receive leronlimab SC weekly with SOC systemic therapy for up to 6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection with HAI pump placement. Starting 4 weeks after surgery, patients receive floxuridine continuously via HAI pump every 14 days of each cycle and resume leronlimab SC weekly in combination with SOC systemic therapy of each cycle. Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and CT and/or MRI throughout the study. Additionally, patients may optionally undergo biopsy on study.
干预措施: Computed Tomography (Procedure)
Treatment (leronlimab, HAI FUDR, systemic therapy)
Patients receive leronlimab SC weekly with SOC systemic therapy for up to 6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection with HAI pump placement. Starting 4 weeks after surgery, patients receive floxuridine continuously via HAI pump every 14 days of each cycle and resume leronlimab SC weekly in combination with SOC systemic therapy of each cycle. Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and CT and/or MRI throughout the study. Additionally, patients may optionally undergo biopsy on study.
干预措施: Intrahepatic Infusion Procedure (Procedure)
Treatment (leronlimab, HAI FUDR, systemic therapy)
Patients receive leronlimab SC weekly with SOC systemic therapy for up to 6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection with HAI pump placement. Starting 4 weeks after surgery, patients receive floxuridine continuously via HAI pump every 14 days of each cycle and resume leronlimab SC weekly in combination with SOC systemic therapy of each cycle. Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and CT and/or MRI throughout the study. Additionally, patients may optionally undergo biopsy on study.
干预措施: Magnetic Resonance Imaging (Procedure)
Treatment (leronlimab, HAI FUDR, systemic therapy)
Patients receive leronlimab SC weekly with SOC systemic therapy for up to 6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection with HAI pump placement. Starting 4 weeks after surgery, patients receive floxuridine continuously via HAI pump every 14 days of each cycle and resume leronlimab SC weekly in combination with SOC systemic therapy of each cycle. Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and CT and/or MRI throughout the study. Additionally, patients may optionally undergo biopsy on study.
干预措施: Surgical Procedure (Procedure)
Treatment (leronlimab, HAI FUDR, systemic therapy)
Patients receive leronlimab SC weekly with SOC systemic therapy for up to 6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection with HAI pump placement. Starting 4 weeks after surgery, patients receive floxuridine continuously via HAI pump every 14 days of each cycle and resume leronlimab SC weekly in combination with SOC systemic therapy of each cycle. Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and CT and/or MRI throughout the study. Additionally, patients may optionally undergo biopsy on study.
干预措施: Systemic Therapy (Procedure)
Treatment (leronlimab, HAI FUDR, systemic therapy)
Patients receive leronlimab SC weekly with SOC systemic therapy for up to 6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection with HAI pump placement. Starting 4 weeks after surgery, patients receive floxuridine continuously via HAI pump every 14 days of each cycle and resume leronlimab SC weekly in combination with SOC systemic therapy of each cycle. Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and CT and/or MRI throughout the study. Additionally, patients may optionally undergo biopsy on study.
干预措施: Floxuridine (Drug)
Treatment (leronlimab, HAI FUDR, systemic therapy)
Patients receive leronlimab SC weekly with SOC systemic therapy for up to 6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection with HAI pump placement. Starting 4 weeks after surgery, patients receive floxuridine continuously via HAI pump every 14 days of each cycle and resume leronlimab SC weekly in combination with SOC systemic therapy of each cycle. Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and CT and/or MRI throughout the study. Additionally, patients may optionally undergo biopsy on study.
干预措施: Leronlimab (Biological)
结局指标
主要结局
Proportion of patients completing all four planned hepatic arterial infusion (HAI) cycles with a relative dose intensity ≥ 80% for HIA floxuridine (FUDR)
时间窗: 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.
次要结局
- Incidence, type, and severity of adverse events (AEs) attributed to HAI(From first dose HAI through 30 days after the last dose of HAI)
- Incidence of serious AEs attributed to HAI(From first dose HAI through 30 days after the last dose of HAI)
- Incidence of AEs attributed to HAI leading to treatment interruption or discontinuation(From first dose HAI through 30 days after the last dose of HAI)
- Incidence, type, and severity of AEs attributed to leronlimab(From first dose leronlimab through 30 days after last dose of leronlimab)
- Incidence of serious AEs attributed to leronlimab(From first dose leronlimab through 30 days after last dose of leronlimab)
- Incidence of AEs leading attributed to leronlimab to treatment interruption or discontinuation(From first dose leronlimab through 30 days after last dose of leronlimab)
- Incidence, type, and severity of AEs attributed to systemic therapy(From first dose systemic therapy through 30 days after last dose of systemic therapy)
- Incidence of serious AEs attributed to systemic therapy(From first dose systemic therapy through 30 days after last dose of systemic therapy)
- Incidence of AEs attributed to systemic therapy leading to treatment interruption or discontuation(From first dose systemic therapy through 30 days after last dose of systemic therapy)
- Incidence and extent of liver toxicity attributed to HAI/FUDR requiring dose reductions based on standard of care nomogram(From the first HAI infusion through 30 days after the final dose of HAI therapy)
- Incidence and characteristics of dose reductions and treatment interruption of HAI/FUDR therapy(From first administration of HAI therapy and up through 30 days after the final administration of HAI therapy)
- Radiographic progression free survival (PFS)(From enrollment to first objective occurrence of tumor progression or death due to any cause, whichever occurs first, assessed up to 1 year)
- Radiographic PFS(From enrollment to first objective occurrence of tumor progression or death due to any cause, whichever occurs first, assessed up to 2 years)
- Median PFS(Up to 24 months)
- Median liver-PFS(Up to 24 months)
- Liver-PFS(From enrollment to the first occurrence of radiographic progression within the liver or death due to any cause, assessed up to 1 year)
- Liver-PFS(From enrollment to the first occurrence of radiographic progression within the liver or death due to any cause, assessed up to 2 years)
- Change in circulating tumor deoxyribonucleic acid (ctDNA)(At baseline (weeks 0, 2, 4, and 6) and post operatively (weeks 2, 4, 6, 8, 10, 12, 14 and 16))
- ctDNA clearance(Up to 24 months)