PUMP-IT RCT: 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
- Conditions
- Colorectal liver metastasesTherapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02]Therapeutic area: Analytical,Diagnostic,Therapeutic Techniques and Equipment [E]-Surgical Procedures, Operative [E04]Therapeutic area: Diseases [C] - Digestive System Diseases [C06]Therapeutic area: Diseases [C] - Neoplasms [C04]
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 306
Age = 18 years., 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). oHb = 5.5 mmol/L oabsolute neutrophil count (ANC) =1.5 x 109/L oplatelets =100 x 109/L ototal bilirubin = 1.5 times the upper limit of normal (ULN) oASAT/AST = 5 x ULN oALAT/ALT = 5 x ULN oalkaline phosphatase = 5 x ULN oSerum creatinine = 1.5 x upper limit of normal or a MDRD (eGFR) = 45 ml/min; oProthrombin 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., Histologically confirmed colorectal adenocarcinoma., Unresectable synchronous colorectal liver metastases 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 1., Life expectancy of at least 12 weeks., Known mutation status of RAS and BRAFV600E.
Prior hepatic radiation, resection, or ablation., 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, 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 an intermediate (N+) or locally advanced rectal tumour (defined as a tumour with at least one of the following characteristics: tumour >5 cm; mesorectal fascia (MRF) ingrowth or ingrowth in adjacent organ on MRI (T4); Nodal positive primary tumour, i.e. at least one lymph node >8 mm or 4 lymph nodes >5 mm on CT scan or MRI.), 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method