Testing Pump Chemotherapy in Addition to Standard of Care Chemotherapy Versus Standard of Care Chemotherapy Alone for Patients With Unresectable Colorectal Liver Metastases: The PUMP Trial

NCT ID: NCT05863195

Last Updated: 2025-11-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

408 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-10-19

Study Completion Date

2034-06-30

Brief Summary

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This phase III trial compares hepatic arterial infusion (HAI) (pump chemotherapy) in addition to standard of care chemotherapy versus standard of care chemotherapy alone in treating patients with colorectal cancer that has spread to the liver (liver metastases) and cannot be removed by surgery (unresectable). HAI uses a catheter to carry a tumor-killing chemotherapy drug called floxuridine directly into the liver. HAI is already approved by the Food and Drug Administration (FDA) for use in metastatic colorectal cancer to the liver, but it is only available at a small number of hospitals, and most of the time it is not used until standard chemotherapy stops working. Standard chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding HAI to standard chemotherapy may be effective in shrinking or stabilizing unresectable colorectal liver metastases.

Detailed Description

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PRIMARY OBJECTIVE:

I. To determine if patients with persistently unresectable colorectal liver metastases (CRLM) after treatment with first-line chemotherapy have improved overall survival (OS) with hepatic arterial infusion (HAI) and systemic chemotherapy versus systemic chemotherapy alone.

SECONDARY OBJECTIVES:

I. To determine whether there is a direct association between hepatic progression free survival (hPFS) and overall survival (OS) when patients are treated with HAI combined with systemic chemotherapy for unresectable CRLM.

II To determine the impact on progression free survival (overall, hepatic and extrahepatic) for patients with unresectable CRLM treated with HAI in combination with systemic chemotherapy.

III. To determine objective response rate (ORR) in the liver, defined as the proportion of patients achieving complete or partial response by Response Evaluation Criteria is Solid Tumors (RECIST) 1.1.

IV. To determine the rate of conversion to resectable disease, defined as the proportion of patients who successfully convert from unresectable to resectable status and undergo R0/R1 resection/ablation.

V. To determine the rate in which patients are intended to be treated with HAI but are deemed ineligible at the time of planned pump insertion due to detection of occult extrahepatic disease or unsuitable arterial anatomy (Intra-Operative Ineligibility, IOI).

VI. To determine the extent to which patient and disease-specific factors correlate with short- and long-term risk of HAI-specific complications.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients undergo surgery to place the HAI pump, followed by single photon emission computed tomography/computed tomography (SPECT/CT) on study. Patients then receive floxuridine via the HAI pump on study. Patients also receive one of the following standard chemotherapy regimens per the treating physician: FOLFOX (fluorouracil intravenously \[IV\], oxaliplatin IV, and leucovorin IV), FOLFIRI (fluorouracil IV, irinotecan IV, and leucovorin IV), or OX/IRI (oxaliplatin IV and irinotecan IV) with or without cetuximab IV and/or panitumumab IV on study. Patients also undergo CT scans throughout the trial.

ARM B: Patients receive one of the following standard chemotherapy regimens per the treating physician: FOLFOXIRI (fluorouracil IV, oxaliplatin IV, irinotecan IV, and leucovorin IV), FOLFOX, FOLFIRI, or OX/IRI with or without cetuximab IV, panitumumab IV, and/or bevacizumab IV on study. Patients also undergo CT scans throughout the trial.

Conditions

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Metastatic Colorectal Carcinoma Metastatic Malignant Neoplasm in the Liver Stage IV Colorectal Cancer AJCC v8 Unresectable Colorectal Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A (HAI, floxuridine, standard chemotherapy)

Patients undergo surgery to place the HAI pump, followed by SPECT/CT on study. Patients then receive floxuridine via the HAI pump on study. Patients also receive one of the following standard chemotherapy regimens per the treating physician: FOLFOX, FOLFIRI, or OX/IRI with or without cetuximab IV and/or panitumumab IV on study. Patients also undergo CT scans throughout the trial.

Group Type EXPERIMENTAL

Cetuximab

Intervention Type BIOLOGICAL

Given IV

Computed Tomography

Intervention Type PROCEDURE

Undergo SPECT/CT and/or CT

Floxuridine

Intervention Type DRUG

Given via HAI pump

Fluorouracil

Intervention Type DRUG

Given IV

Implantation

Intervention Type PROCEDURE

Undergo surgery to place the HAI pump

Intrahepatic Infusion Procedure

Intervention Type PROCEDURE

Undergo HAI

Irinotecan

Intervention Type DRUG

Given IV

Leucovorin

Intervention Type DRUG

Given IV

Oxaliplatin

Intervention Type DRUG

Given IV

Panitumumab

Intervention Type BIOLOGICAL

Given IV

Single Photon Emission Computed Tomography

Intervention Type PROCEDURE

Undergo SPECT/CT

Arm B (standard chemotherapy)

Patients receive one of the following standard chemotherapy regimens per the treating physician: FOLFOXIRI, FOLFOX, FOLFIRI, or OX/IRI with or without cetuximab IV, panitumumab IV, and/or bevacizumab IV on study. Patients also undergo CT scans throughout the trial.

Group Type ACTIVE_COMPARATOR

Bevacizumab

Intervention Type BIOLOGICAL

Given IV

Cetuximab

Intervention Type BIOLOGICAL

Given IV

Computed Tomography

Intervention Type PROCEDURE

Undergo SPECT/CT and/or CT

Fluorouracil

Intervention Type DRUG

Given IV

Irinotecan

Intervention Type DRUG

Given IV

Leucovorin

Intervention Type DRUG

Given IV

Oxaliplatin

Intervention Type DRUG

Given IV

Panitumumab

Intervention Type BIOLOGICAL

Given IV

Interventions

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Bevacizumab

Given IV

Intervention Type BIOLOGICAL

Cetuximab

Given IV

Intervention Type BIOLOGICAL

Computed Tomography

Undergo SPECT/CT and/or CT

Intervention Type PROCEDURE

Floxuridine

Given via HAI pump

Intervention Type DRUG

Fluorouracil

Given IV

Intervention Type DRUG

Implantation

Undergo surgery to place the HAI pump

Intervention Type PROCEDURE

Intrahepatic Infusion Procedure

Undergo HAI

Intervention Type PROCEDURE

Irinotecan

Given IV

Intervention Type DRUG

Leucovorin

Given IV

Intervention Type DRUG

Oxaliplatin

Given IV

Intervention Type DRUG

Panitumumab

Given IV

Intervention Type BIOLOGICAL

Single Photon Emission Computed Tomography

Undergo SPECT/CT

Intervention Type PROCEDURE

Other Intervention Names

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ABP 215 Anti-VEGF Anti-VEGF Humanized Monoclonal Antibody Anti-VEGF Monoclonal Antibody SIBP04 Anti-VEGF rhuMAb Avastin Bevacizumab awwb Bevacizumab Biosimilar ABP 215 Bevacizumab Biosimilar BEVZ92 Bevacizumab Biosimilar BI 695502 Bevacizumab Biosimilar CBT 124 Bevacizumab Biosimilar CT-P16 Bevacizumab Biosimilar FKB238 Bevacizumab Biosimilar GB-222 Bevacizumab Biosimilar HD204 Bevacizumab Biosimilar HLX04 Bevacizumab Biosimilar IBI305 Bevacizumab Biosimilar LY01008 Bevacizumab Biosimilar MIL60 Bevacizumab Biosimilar Mvasi Bevacizumab Biosimilar MYL-1402O Bevacizumab Biosimilar QL 1101 Bevacizumab Biosimilar QL1101 Bevacizumab Biosimilar RPH-001 Bevacizumab Biosimilar SCT501 Bevacizumab Biosimilar Zirabev Bevacizumab-awwb Bevacizumab-bvzr BP102 BP102 Biosimilar HD204 Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer Mvasi MYL-1402O QL1101 Recombinant Humanized Anti-VEGF Monoclonal Antibody rhuMab-VEGF SCT501 SIBP 04 SIBP-04 SIBP04 Zirabev Cetuximab Biosimilar CDP-1 Cetuximab Biosimilar CMAB009 Cetuximab Biosimilar KL 140 Chimeric Anti-EGFR Monoclonal Antibody Chimeric MoAb C225 Chimeric Monoclonal Antibody C225 Erbitux IMC-C225 CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography CT CT Scan tomography 2'-Deoxy-5-fluorouridine 5-Fluoro-2'-deoxyuridine 5-Fluorodeoxyuridine 5-Fluorouracil deoxyriboside 5-FUdR FDUR Floxuridin Fluorodeoxyuridine Fluorouridine Deoxyribose Fluoruridine Deoxyribose FUdR WR-138720 5 Fluorouracil 5 Fluorouracilum 5 FU 5-Fluoro-2,4(1H, 3H)-pyrimidinedione 5-Fluorouracil 5-Fluracil 5-Fu 5FU AccuSite Carac Fluoro Uracil Fluouracil Flurablastin Fluracedyl Fluracil Fluril Fluroblastin Ribofluor Ro 2-9757 Ro-2-9757 HAI Hepatic Arterial Infusion Hepatic Artery Infusion IHI Intrahepatic Infusion Folinic acid 1-OHP Ai Heng Aiheng Dacotin Dacplat Diaminocyclohexane Oxalatoplatinum Eloxatin Eloxatine JM-83 Oxalatoplatin Oxalatoplatinum RP 54780 RP-54780 SR-96669 ABX-EGF ABX-EGF Monoclonal Antibody ABX-EGF, Clone E7.6.3 E7.6.3 Human IgG2K Monoclonal Antibody MoAb ABX-EGF MoAb E7.6.3 Monoclonal Antibody ABX-EGF Monoclonal Antibody E7.6.3 Vectibix Medical Imaging, Single Photon Emission Computed Tomography Single Photon Emission Tomography Single-Photon Emission Computed single-photon emission computed tomography SPECT SPECT imaging SPECT SCAN SPET ST tomography, emission computed, single photon Tomography, Emission-Computed, Single-Photon

Eligibility Criteria

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Inclusion Criteria

* Patient must be \>= 18 years of age
* Patient must have confirmed unresectable liver confined metastatic colorectal cancer (CRC).

* Patient must not have radiographically or clinically evident extrahepatic disease (including but not limited to radiographically positive periportal lymph nodes).

* NOTE: Patients found to have positive periportal nodes at the time of HAI placement can remain on study.
* Patient may have calcified pulmonary nodules, and/or =\< 5 indeterminate and stable (for a minimum of 3 months on chemotherapy) pulmonary nodules each measuring =\< 6 mm in maximal axial dimension.
* Patient's primary tumor may be in place.
* Patient must have received 3-6 months of previous first-line chemotherapy that meet one of the following three criteria: a) have received at least 6 but no more than 12 cycles of first-line cytotoxic chemotherapy (where 1 cycle = 14 days) OR b) have received at least 4 but no more than 8 cycles of first-line cytotoxic chemotherapy (where 1 cycle = 21 days) OR c) have developed new colorectal liver metastases (CRLM) within 12 months of completing adjuvant systemic therapy for stage II-III colorectal cancer.

* NOTE: First-line chemotherapy may have included any of the following regimens as listed in the National Comprehensive Cancer Network (NCCN) Guidelines: leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX) (or equivalent), leucovorin calcium (calcium folinate), 5-fluorouracil, and irinotecan (FOLFIRI) (or equivalent), leucovorin calcium (calcium folinate), 5-fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI), each with or without any of the following: bevacizumab, cetuximab, or panitumumab.
* Patient must have stable or responding disease on first-line chemotherapy by RECIST 1.1 criteria
* Patient must meet the following criteria for technical unresectability:

* A margin-negative resection requires resection of three hepatic veins, both portal veins, or the retrohepatic vena cava OR a resection that leaves less than two adequately perfused and drained segments.
* NOTE: Institutional multidisciplinary review is required to confirm unresectability and rule out radiographically positive extrahepatic disease.
* Patient must undergo CT angiography (chest/abdomen/pelvis) to confirm acceptable hepatic arterial anatomy for HAI and to rule out extrahepatic disease within 4 weeks prior to randomization.
* Patient must have an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 and be clinically fit to undergo surgery as determined by the pre-operative evaluation.
* Leukocytes \>= 3,000/mcL (obtained =\< 14 days prior to protocol randomization)
* Absolute neutrophil count (ANC) \>= 1,500/mcL (obtained =\< 14 days prior to protocol randomization)
* Platelets \>= 100,000/mcL (obtained =\< 14 days prior to protocol randomization)
* Total Bilirubin =\< 1.5 mg/dL (obtained =\< 14 days prior to protocol randomization)
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) =\< 3.0 x institutional upper limit of normal (ULN) (obtained =\< 14 days prior to protocol randomization)
* Creatinine =\< 1.5 x institutional ULN OR creatinine clearance \>= 50 mL/min calculated by the Cockcroft-Gault method (obtained =\< 14 days prior to protocol randomization)
* Calcium \>= institutional lower limit of normal (LLN)
* 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.
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial. Testing for HIV is not required for entry onto the study

Exclusion Criteria

* Patient must not have a liver tumor burden exceeding 70% of total liver volume.
* Patient must not have had prior radiation to the liver (prior radiation therapy to the pelvis is acceptable if completed at least 2 weeks prior to randomization).
* Patient must not have had prior trans-arterial bland embolization, chemoembolization (TACE) or radioembolization (TARE).
* Patient must not have had prior treatment with HAI/floxuridine (FUDR)
* Patient must not have microsatellite instability-high (MSI-H) colorectal cancer.
* Patient must not have CRLM that could be resected with 2-stage hepatectomy, including associating liver partition and portal vein ligation (ALPPS).
* Patient must not have an active infection, serious or non-healing active wound, ulcer, or bone fracture.
* Patient must not have any serious medical problems which would preclude receiving the protocol treatment or would interfere with the cooperation with the requirements of this trial.
* Patient must not have cirrhosis and/or clinical or radiographic evidence of portal hypertension
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used.

* All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy.
* A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
* Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

ECOG-ACRIN Cancer Research Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael Lidsky

Role: PRINCIPAL_INVESTIGATOR

ECOG-ACRIN Cancer Research Group

Locations

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University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Site Status RECRUITING

UCHealth University of Colorado Hospital

Aurora, Colorado, United States

Site Status RECRUITING

UM Sylvester Comprehensive Cancer Center at Aventura

Aventura, Florida, United States

Site Status RECRUITING

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, United States

Site Status RECRUITING

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, United States

Site Status RECRUITING

UM Sylvester Comprehensive Cancer Center at Hollywood

Hollywood, Florida, United States

Site Status RECRUITING

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

Site Status RECRUITING

UM Sylvester Comprehensive Cancer Center at Kendall

Miami, Florida, United States

Site Status RECRUITING

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, United States

Site Status RECRUITING

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Site Status RECRUITING

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status RECRUITING

Memorial Hospital East

Shiloh, Illinois, United States

Site Status RECRUITING

IU Health North Hospital

Carmel, Indiana, United States

Site Status RECRUITING

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status RECRUITING

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, United States

Site Status RECRUITING

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status RECRUITING

Corewell Health Grand Rapids Hospitals - Butterworth Hospital

Grand Rapids, Michigan, United States

Site Status RECRUITING

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status RECRUITING

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, United States

Site Status RECRUITING

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, United States

Site Status RECRUITING

Washington University School of Medicine

St Louis, Missouri, United States

Site Status RECRUITING

Siteman Cancer Center-South County

St Louis, Missouri, United States

Site Status RECRUITING

Siteman Cancer Center at Christian Hospital

St Louis, Missouri, United States

Site Status RECRUITING

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, United States

Site Status RECRUITING

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, United States

Site Status RECRUITING

Memorial Sloan Kettering Bergen

Montvale, New Jersey, United States

Site Status RECRUITING

Memorial Sloan Kettering Commack

Commack, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Westchester

East White Plains, New York, United States

Site Status RECRUITING

Mount Sinai Hospital

New York, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Nassau

Uniondale, New York, United States

Site Status RECRUITING

Duke University Medical Center

Durham, North Carolina, United States

Site Status RECRUITING

Case Western Reserve University

Cleveland, Ohio, United States

Site Status ACTIVE_NOT_RECRUITING

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

West Penn Hospital

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

Site Status RECRUITING

Parkland Memorial Hospital

Dallas, Texas, United States

Site Status RECRUITING

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

Site Status RECRUITING

Countries

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United States

Facility Contacts

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Other Identifiers

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NCI-2023-02357

Identifier Type: REGISTRY

Identifier Source: secondary_id

EA2222

Identifier Type: OTHER

Identifier Source: secondary_id

EA2222

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180820

Identifier Type: NIH

Identifier Source: secondary_id

View Link

EA2222

Identifier Type: -

Identifier Source: org_study_id