NCT06857773招募中3 期
Hepatic Arterial Infusion PUMP Chemotherapy Combined with Systemic Therapy Versus Systemic Therapy Alone As Induction Therapy for Initially Unresectable Colorectal Liver Metastases: a Randomised Controlled Trial
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 306
- 试验地点
- 1
- 主要终点
- Overall survival
研究概览
简要总结
The goal of this randomized clinical trial is to investigate induction treatment with Hepatic Arterial Infusion Pump therapy combined with systemic therapy (HAIP-SYST) in chemotherapy-naive patients with unresectable colorectal liver metastases without extrahepatic disease. The main question it aims to answer is if combined HAIP-SYST improves survival compared to induction treatment with systemic therapy alone. Patients in the control arm will receive systemic therapy according to standard of care.
Study procedures experimental arm
- Surgery for pump placement and resection of the primary tumor
- Pre- and postoperative imaging (CT-anghiography, 99mTc-MAA scintigraphy)
- Induction treatment with hepatic arterial infusion pump therapy with Floxuridine combined with systemic therapy
Study procedures both arms
- Evaluation of resectability status by a National Liver Panel with surgeons and radiologists
- Questionnaires for Quality of Life
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Age ≥ 18 years.
- •Histologically confirmed colorectal adenocarcinoma.
- •Unresectable synchronous CRLM according to a National Liver Panel (CT-scan obtained ≤ 4 weeks prior to registration).
- •No extrahepatic metastases. Patients with small (≤ 10 mm) extrahepatic lesions that are not clearly suspicious of metastases are eligible.
- •No previous systemic therapy for colorectal cancer.
- •Positioning of a catheter for HAIP chemotherapy is technically feasible based on imaging. The default site for the catheter insertion is the gastroduodenal artery (GDA). Accessory or aberrant hepatic arteries are no contra-indication for catheter implantation. The GDA should have at least one branch to the liver. Accessory or aberrant hepatic arteries should be ligated to allow for cross perfusion to the entire liver through intrahepatic shunts. Patients with celiac trunk stenosis are not eligible. Patients with both a replaced right and replaced left hepatic artery are not eligible.
- •ECOG performance status 0 or
- •Life expectancy of at least 12 weeks.
- •Known mutation status of RAS and BRAFV600E.
- •Primary tumour in situ and resectable without neoadjuvant therapy.
- •Patient is eligible for surgery.
- •Patient is eligible for doublet chemotherapy.
- •Laboratory requirements: i.e. adequate bone marrow, liver and renal function (obtained within 15 days prior to registration).
- •Hb ≥ 5.5 mmol/L
- •absolute neutrophil count (ANC) ≥1.5 x 109/L
- •platelets ≥100 x 109/L
- •total bilirubin ≤ 1.5 times the upper limit of normal (ULN)
- •ASAT/AST ≤ 5 x ULN
- •ALAT/ALT ≤ 5 x ULN
- •alkaline phosphatase ≤ 5 x ULN
- •Serum creatinine ≤ 1.5 x upper limit of normal or a MDRD (eGFR) ≥ 45 ml/min;
- •Prothrombin time or INR < 1.5 x ULN, unless coumarin derivates are used. All patients using coumarin derivates will be treated with LMWH or DOAC instead.
- •Before registration, written informed consent must be given and signed according to ICH/GCP, and national/local regulations.
排除标准
- •Prior hepatic radiation, resection, or ablation.
- •Any malignancy, comorbidity or condition that interferes with the planned study treatment or the prognosis of CRLM, determined by the treating physician.
- •History of prior malignancy except for the following: (a) malignancy treated with curative intent and with no evidence of active disease present within 3 years prior to inclusion, (b) curatively treated malignancies felt to be at low risk for recurrence by treating physician and MDT, (c) adequately controlled nonmelanomatous skin cancer, (d) adequately treated carcinoma in situ without current evidence of disease.
- •Obstructive primary tumour requiring emergency surgery, primary tumour necessitating a multivisceral resection/abdominoperineal resection or a rectal tumour requiring preoperative short-course radiotherapy or chemoradiotherapy for local tumour control.
- •MMR deficiency.
- •DPD-deficiency.
- •Pregnant or lactating women.
- •Serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator.
- •Organ allografts requiring immunosuppressive therapy.
- •Serious non-healing wound, ulcer, or bone fracture.
- •Chronic treatment with corticosteroids (dose of ≥ 10 mg/day methylprednisolone equivalent excluding inhaled steroids).
- •Known serious infections (uncontrolled or requiring treatment).
- •History of psychiatric disability judged by the investigator to be clinically significant, precluding informed consent or interfering with compliance for HAIP-SYST or standard systemic therapy.
- •Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
- •Underlying liver disease including liver fibrosis and cirrhosis
研究组 & 干预措施
A: systemic therapy according to standard of care
Active Comparator
Patients included in the control arm will receive systemic therapy according to standard of care
干预措施: Systemic therapy (standard of care) (Drug)
B: combined HAIP-therapy and systemic therapy
Experimental
Patients included in the experimental arm undergo surgery for pump placement and resection of the primary tumor. Followed by combined induction treatment with floxuridine via the hepatic arterial infusion pump (1cycle is 4 weeks) and systemic therapy (FOLFOX or FOLFIRI, 1 cycle is 2 weeks)
干预措施: Intra arterial infusion Floxuridine (FUDR) combined with systemic therapy (Drug)
B: combined HAIP-therapy and systemic therapy
Experimental
Patients included in the experimental arm undergo surgery for pump placement and resection of the primary tumor. Followed by combined induction treatment with floxuridine via the hepatic arterial infusion pump (1cycle is 4 weeks) and systemic therapy (FOLFOX or FOLFIRI, 1 cycle is 2 weeks)
干预措施: Hepatic arterial infusion pump (HAIP) (Device)
结局指标
主要结局
Overall survival
时间窗: Up to five years after randomization
Defined as the time between randomization and the event of death.
次要结局
- Progression-free survival(Up to five years after randomization)
- Hepatic progression-free survival(Up to five years after randomization)
- Conversion to resection rate(if CRLM convert to resectable, often at 3-6 months after start induction treatment)
- Complete local treatment rate(if CRLM convert to resectable, often at 3-6 months after start induction treatment)
- Objective response rate (ORR)(During protocol treatment, up to 6 months of induction treatment)
- Disease control rate (DCR)(During protocol treatment, up to 6 months of induction treatment)
- Pathological response rate(Pathological assessment of conversion surgery after induction treatment)
- Surgical complication rate(at 30 days an 90 days postoperatively)
- Adverse events and toxicity of HAIP-SYST and systemic therapy(During protocol treatment)
- Quality of Life (QoL)(Up to five years after randomization)
- Cost-effectiveness(Up to five years after randomization)
研究者
研究点 (1)
Loading locations...
相似试验
已完成
1 期
Hepatic Arterial Infusion Oxaliplatin, Capecitabine With or Without BevacizumabAdvanced CancersNCT01213238M.D. Anderson Cancer Center116
已完成
2 期
HAIC Combine With Lenvatinib and PD-1 Inhibitors for Advanced HCC With PVTTHepatocellular CarcinomaPortal Vein ThrombosisNCT05166239Peking University66
尚未招募
2 期
HAIC+Adebrelimab+Lenvatinib for Conversion Treatment of Potentially Resectable, Locally Advanced Biliary Tract CancerBiliary Tract CancerNCT06389500Harbin Medical University30
Unknown
2 期
Hepatic Arterial Infusion Pump Chemotherapy Combined With Systemic Chemotherapy (PUMP-IT)Colorectal NeoplasmsNCT04552093The Netherlands Cancer Institute31
招募中
不适用
HAIC in Combination with PD-1 Inhibitors and Lenvatinib for Intermediate and Advanced HCC After the Failure of Systemic Therapy Recommended by BCLCBCLC Stage B Hepatocellular CarcinomaBCLC Stage C Hepatocellular CarcinomaHepatic Arterial Infusion ChemotherapyLenvatinibPD-1Systemic TherapyNCT06632093First Hospital of China Medical University84