Colorectal NeoplasmsPhase 3PUMP-IT RCTNCT06857773
Induction Treatment for Initially Unresectable Colorectal Liver Metastases: Combined Hepatic Arterial Infusion Pump Therapy With Systemic Therapy
A Phase 3 study testing Intra arterial infusion Floxuridine (FUDR) combined with systemic therapy and Hepatic arterial infusion pump (HAIP) in people with Colorectal Neoplasms and Floxuridine, run by The Netherlands Cancer Institute at 1 site in Netherlands.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Neoplasms, Floxuridine, Liver Metastases
- What is being tested?
- Intra arterial infusion Floxuridine (FUDR) combined with systemic therapy and Hepatic arterial infusion pump (HAIP)
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 306 participants
- Where
- 1 siteNetherlands
- Study dates
- 21 Nov 2024to Jan 2035
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 23Show fewer
- ECOG performance status 0 or 1.
- 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.
Who cannot join
- 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.
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Antoni van Leeuwenhoek-Netherland Cancer Institute
Amsterdam, 1066CX
Elisa M ter Kuile, +3120 512 9111, pump@nki.nl
Koert FD Kuhlmann
About this study
Official title: 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
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
Read more
- 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
- Being tested
- Intra arterial infusion Floxuridine (FUDR) combined with systemic therapy, Hepatic arterial infusion pump (HAIP), Systemic therapy (standard of care)
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intra arterial infusion Floxuridine (FUDR) combined with systemic therapyDrug
Floxuridine is administered via the hepatic arterial infusion pump directly to the hepatic artery with a continous flowrate for a period of 2 weeks. Intra arterial infusion of FUDR is combined with systemic therapy (FOLFOX/FOLFIRI) intravenously. Administration of FUDR via the chemopump is every 4 weeks and systemic therapy is administered every 2 weeks.
Hepatic arterial infusion pump (HAIP)Device
The HAIP (pump) is implanted during surgery combined with resection of the primary tumor before start of induction treatment with Floxuridine and concomitant systemic therapy
Systemic therapy (standard of care)Drug
Patient included in the control arm will receive systemic therapy according to standard clinical practice. Induction therapy regimens include: CAPOX (3 weekly) or FOLFOX/FOLFIRI/FOLFOXIRI (2weekly) with optional addition of Bevacizumab (2 weekly)
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Systemic therapy (standard of care) |
| 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) Receives: Drug: Intra arterial infusion Floxuridine (FUDR) combined with systemic therapy; Device: Hepatic arterial infusion pump (HAIP) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
Defined as the time between randomization and the event of death.
Measured: Up to five years after randomization
Secondary outcomes (11)
Progression-free survival
Defined as the time between randomization and the first event defined as recurrence or death, whichever comes first.
Measured: Up to five years after randomization
Hepatic progression-free survival
Defined as the time between randomization and the event of progression confined to the liver.
Measured: Up to five years after randomization
Conversion to resection rate
Defined as conversion surgery with intention of complete local treatment of all CRLM
Measured: if CRLM convert to resectable, often at 3-6 months after start induction treatment
Complete local treatment rate
R0/1 resection or ablation of all visible CRLM
Measured: if CRLM convert to resectable, often at 3-6 months after start induction treatment
Objective response rate (ORR)
Defined as complete or partial response according to RECIST 1.1
Measured: During protocol treatment, up to 6 months of induction treatment
Disease control rate (DCR)
Defined as a complete or partial and stable disease
Measured: During protocol treatment, up to 6 months of induction treatment
Pathological response rate
Defined as a major and complete pathological response of resected lesions according to the Mandard score.
Measured: Pathological assessment of conversion surgery after induction treatment
Surgical complication rate
of HAIP placement and/or any tumour related surgery. Defined as the percentage of surgery-related (HAIP placement and/or any protocol tumor related surgery) complications grade ≥3 according to the Clavien-Dindo classification
Measured: at 30 days an 90 days postoperatively
Adverse events and toxicity of HAIP-SYST and systemic therapy
Defined as the percentage of treatment related AEs grade ≥ 3 according to Common Terminology Criteria for Adverse Events (CTCAE), version 5.0
Measured: During protocol treatment
Quality of Life (QoL)
Assessed by standardized Quality of Life questionnaires (EORTC QLQ-C30 \& EQ-5D3L)
Measured: Up to five years after randomization
Cost-effectiveness
Expressed by costs per quality adjusted life years (QALYs) and estimated according to the Health Technology Assessment (HTA) methods. Productivity loss is assessed by adjusted standardized Productivity Costs Questionnaires (iPCQ)
Measured: Up to five years after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2025
- Study start21 Nov 2024
- Primary completionJan 2030 (estimated)
- Study completionJan 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal NeoplasmsStudies of the same condition, open and under way.
- More trials run by The Netherlands Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 306 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06857773
- Sponsor's protocol ID
- M23PIT
- Other IDs
- 2023-506194-35-00, 2023
- Acronym
- PUMP-IT RCT
- Status last verified
- Feb 2025
- First submitted
- 1 Aug 2024
- Last updated
- 4 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Ter Kuile EM, Kok N, Westerink B, Swijnenburg RJ, Daletzakis A, Jacobs B, Retel VP, van Golen LW, Snaebjornsson P, Klompenhouwer EG, Koerkamp BG, Buffart TE, Punt C, Verhoef C, Bolhuis K, Kuhlmann K; Dutch PUMP-IT study group. Hepatic arterial infusion pump chemotherapy combined with systemic therapy versus systemic therapy alone as induction treatment for initially unresectable colorectal liver metastases: a study protocol of the randomised controlled trial - PUMP-IT RCT. BMC Cancer. 2026 May 16;26(1):827. doi: 10.1186/s12885-026-16130-y.
PubMed 42143303
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06857773
- Acronym / sponsor ID
- PUMP-IT RCT / M23PIT
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 306 participants (estimated)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Study start
- 21 Nov 2024 (actual)
- Primary completion
- Jan 2030 (estimated)
- Study completion
- Jan 2035 (estimated)
- First posted
- 4 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A: systemic therapy according to standard of care | Active comparator | Drug: Systemic therapy (standard of care)Patients included in the control arm will receive systemic therapy according to standard of care |
| B: combined HAIP-therapy and systemic therapy | Experimental | Drug: Intra arterial infusion Floxuridine (FUDR) combined with systemic therapy, Device: Hepatic arterial infusion pump (HAIP)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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intra arterial infusion Floxuridine (FUDR) combined with systemic therapyFloxuridine is administered via the hepatic arterial infusion pump directly to the hepatic artery with a continous flowrate for a period of 2 weeks. Intra arterial infusion of FUDR is combined with systemic therapy (FOLFOX/FOLFIRI) intravenously. Administration of FUDR via the chemopump is every 4 weeks and systemic therapy is administered every 2 weeks. | Drug | B: combined HAIP-therapy and systemic therapy |
| Hepatic arterial infusion pump (HAIP)The HAIP (pump) is implanted during surgery combined with resection of the primary tumor before start of induction treatment with Floxuridine and concomitant systemic therapy | Device | B: combined HAIP-therapy and systemic therapy |
| Systemic therapy (standard of care)Patient included in the control arm will receive systemic therapy according to standard clinical practice. Induction therapy regimens include: CAPOX (3 weekly) or FOLFOX/FOLFIRI/FOLFOXIRI (2weekly) with optional addition of Bevacizumab (2 weekly) | Drug | A: systemic therapy according to standard of care |
Primary outcome
Overall survival
Time frame: Up to five years after randomization
Defined as the time between randomization and the event of death.
11 secondary outcomes
Progression-free survival
Time frame: Up to five years after randomization
Hepatic progression-free survival
Time frame: Up to five years after randomization
Conversion to resection rate
Time frame: if CRLM convert to resectable, often at 3-6 months after start induction treatment
Complete local treatment rate
Time frame: if CRLM convert to resectable, often at 3-6 months after start induction treatment
Objective response rate (ORR)
Time frame: During protocol treatment, up to 6 months of induction treatment
Disease control rate (DCR)
Time frame: During protocol treatment, up to 6 months of induction treatment
Pathological response rate
Time frame: Pathological assessment of conversion surgery after induction treatment
Surgical complication rate
Time frame: at 30 days an 90 days postoperatively
Adverse events and toxicity of HAIP-SYST and systemic therapy
Time frame: During protocol treatment
Quality of Life (QoL)
Time frame: Up to five years after randomization
Cost-effectiveness
Time frame: Up to five years after randomization
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2025.
- Derived from this study: PubMed 42143303Ter Kuile EM, Kok N, Westerink B, Swijnenburg RJ, Daletzakis A, Jacobs B, Retel VP, van Golen LW, Snaebjornsson P, Klompenhouwer EG, Koerkamp BG, Buffart TE, Punt C, Verhoef C, Bolhuis K, Kuhlmann K; Dutch PUMP-IT study group. Hepatic arterial infusion pump chemotherapy combined with systemic therapy versus systemic therapy alone as induction treatment for initially unresectable colorectal liver metastases: a study protocol of the randomised controlled trial - PUMP-IT RCT. BMC Cancer. 2026 May 16;26(1):827. doi: 10.1186/s12885-026-16130-y.
Related trials for Colorectal Neoplasms
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingObservational study
Pre- and On-treatment Multi-omics Profiling of Locally Advanced Rectal Cancer
Rectal Neoplasms
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 2
Tislelizumab in People With Colorectal Cancer
Colorectal Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Intra arterial infusion Floxuridine (FUDR) combined with systemic therapy and Hepatic arterial infusion pump (HAIP) in people with Colorectal Neoplasms and Floxuridine, run by The Netherlands Cancer Institute at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Koert FD Kuhlmann, MD PhD (+31205129111, pump@nki.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (time frame: Up to five years after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06857773, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2025.