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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
EU CTIS ID: 2023-506194-35-00
What this study is testing
To investigate whether HAIP-SYST prolongs survival in chemo-naive patients with initially unresectable colorectal liver metastases as compared with systemic therapy alone.
- Therapeutic confirmatory (Phase III)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Age ≥ 18 years ≤ 75 years
- Primary tumour in situ and resectable without neoadjuvant therapy.
- Patient is eligible for surgery, as assessed by the treating surgeon
- Patient is eligible for at least doublet chemotherapy, as assessed by the treating oncologist.
- Laboratory requirements: i.e. adequate bone marrow, liver and renal function (obtained within 15 days prior to registration for screening). o Hb ≥ 5.5 mmol/L o absolute neutrophil count (ANC) ≥1.5 x 109/L o platelets ≥100 x 109/L o total bilirubin ≤ 1.5 times the upper limit of normal (ULN) o ASAT/AST ≤ 5 x ULN o ALAT/ALT ≤ 5 x ULN o alkaline phosphatase ≤ 5 x ULN o Serum creatinine ≤ 1.5 x upper limit of normal or a MDRD (eGFR) ≥ 45 ml/min; o Prothrombin time or INR < 1.5 x ULN (> 1.5 x ULN accepted for patients treated with coumarin derivates. These patients 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.
You likely can't join if
- Prior hepatic radiation, resection, or ablation.
- 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.
See the full eligibility criteria
Who can join
- Age ≥ 18 years ≤ 75 years
- Primary tumour in situ and resectable without neoadjuvant therapy.
- Patient is eligible for surgery, as assessed by the treating surgeon
- Patient is eligible for at least doublet chemotherapy, as assessed by the treating oncologist.
- Laboratory requirements: i.e. adequate bone marrow, liver and renal function (obtained within 15 days prior to registration for screening). o Hb ≥ 5.5 mmol/L o absolute neutrophil count (ANC) ≥1.5 x 109/L o platelets ≥100 x 109/L o total bilirubin ≤ 1.5 times the upper limit of normal (ULN) o ASAT/AST ≤ 5 x ULN o ALAT/ALT ≤ 5 x ULN o alkaline phosphatase ≤ 5 x ULN o Serum creatinine ≤ 1.5 x upper limit of normal or a MDRD (eGFR) ≥ 45 ml/min; o Prothrombin time or INR < 1.5 x ULN (> 1.5 x ULN accepted for patients treated with coumarin derivates. These patients 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 Liver Expert Panel (CT-scan obtained ≤ 4 weeks prior to registration for screening), defined as: o CRLM that are potentially resectable or locally treatable with two-stage approach, with resection and/or ablation or after portal vein embolization AND for which starting with systemic therapy is preferred because of the number, size, location or distribution of the metastases. o CRLM that are technically untreatable with local therapies without first downsizing
- 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 contraindication 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. Not eligible: o Patients with significant (>50%) celiac trunk or superior mesenteric artery (SMA) stenosis o Patients with any celiac trunk stenosis and a replaced or accessory hepatic artery o Patients with both a replaced right and replaced left hepatic artery. A CT arterial phase is mandatory before randomisation in case of any celiac trunk or SMA stenosis. The sponsor study team is consulted in case of doubt about technical feasibility.
- ECOG performance status 0 or 1.
- Life expectancy of at least 12 weeks.
- Known mutation status of RAS and BRAFV600E.
What rules you out
- Prior hepatic radiation, resection, or ablation.
- 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.
- History of clinically significant cardiovascular disease including, but not limited to, the following: New York Heart Association Heart Failure Class 2 or greater (Appendix G), major cardiovascular events or interventions within 6 months prior to registration for screening (e.g. myocardial infarction, endarterectomy) randomisation, unstable arrhythmias or unstable angina.
- 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 comorbidity or condition that interferes with the planned study treatment or the prognosis of CRLM, determined by the treating physician.
- Prior or concurrent second malignancy other than the disease under study or one whose natural history or treatment is likely to interfere with any study endpoints of safety or the efficacy of the study treatment(s) as discussed in the local MDT. The following malignancies are allowed: (a) malignancy treated with curative intent and with no evidence of active disease present within 3 years prior to inclusion (b) adequately controlled nonmelanomatous skin cancer (c) adequately treated carcinoma in situ without current evidence of disease Prior or concurrent second malignancies other than (a), (b) and (c) must be reviewed and agreed to with the sponsor study team.
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.