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

NCT05863195 | Recruiting Phase 3 FDA Drug

• 3 other identifiers: EA2222NCI-2023-02357U10CA180820
• Study Type: interventional
• Target: 408
• Locations: 1 country
• Sites: 39

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  Patients still living will be censored at the date last known alive. OS will be evaluated using the Kaplan-Meier method, and arms will be compared via a stratified log rank test.

  From randomization to death from any cause, assessed up to 5 years

Secondary Outcomes (7)

• Progression free survival (PFS)

  From randomization to first observed disease progression at any site, or death from any cause, assessed up to 5 years

• Hepatic PFS

  From randomization to first observed disease progression in the liver, or death from any cause, assessed up to 5 years

• Extrahepatic-PFS

  From randomization to first observed disease progression outside of the liver, or death from any cause, assessed up to 5 years

• Objective response rate

  Up to 5 years

• Rate of conversion to resectable disease

  Up to 5 years

Study Arms (2)

Arm A (HAI, floxuridine, standard chemotherapy)

EXPERIMENTAL

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.

Biological: Cetuximab; Procedure: Computed Tomography; Drug: Floxuridine; Drug: Fluorouracil; Procedure: Implantation; Procedure: Intrahepatic Infusion Procedure; Drug: Irinotecan; Drug: Leucovorin; Drug: Oxaliplatin; Biological: Panitumumab; Procedure: Single Photon Emission Computed Tomography

Arm B (standard chemotherapy)

ACTIVE COMPARATOR

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.

Biological: Bevacizumab; Biological: Cetuximab; Procedure: Computed Tomography; Drug: Fluorouracil; Drug: Irinotecan; Drug: Leucovorin; Drug: Oxaliplatin; Biological: Panitumumab

Interventions

Bevacizumab BIOLOGICAL

Given IV

Also known as: 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

Arm B (standard chemotherapy)

Cetuximab BIOLOGICAL

Given IV

Also known as: 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

Arm A (HAI, floxuridine, standard chemotherapy); Arm B (standard chemotherapy)

Computed Tomography PROCEDURE

Undergo SPECT/CT and/or CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Arm A (HAI, floxuridine, standard chemotherapy); Arm B (standard chemotherapy)

Floxuridine DRUG

Given via HAI pump

Also known as: 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

Arm A (HAI, floxuridine, standard chemotherapy)

Fluorouracil DRUG

Given IV

Also known as: 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

Arm A (HAI, floxuridine, standard chemotherapy); Arm B (standard chemotherapy)

Implantation PROCEDURE

Undergo surgery to place the HAI pump

Arm A (HAI, floxuridine, standard chemotherapy)

Intrahepatic Infusion Procedure PROCEDURE

Undergo HAI

Also known as: HAI, Hepatic Arterial Infusion, Hepatic Artery Infusion, IHI, Intrahepatic Infusion

Arm A (HAI, floxuridine, standard chemotherapy)

Irinotecan DRUG

Given IV

Arm A (HAI, floxuridine, standard chemotherapy); Arm B (standard chemotherapy)

Leucovorin DRUG

Given IV

Also known as: Folinic acid

Arm A (HAI, floxuridine, standard chemotherapy); Arm B (standard chemotherapy)

Oxaliplatin DRUG

Given IV

Also known as: 1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669

Arm A (HAI, floxuridine, standard chemotherapy); Arm B (standard chemotherapy)

Panitumumab BIOLOGICAL

Given IV

Also known as: 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

Arm A (HAI, floxuridine, standard chemotherapy); Arm B (standard chemotherapy)

Single Photon Emission Computed Tomography PROCEDURE

Undergo SPECT/CT

Also known as: 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

Arm A (HAI, floxuridine, standard chemotherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• ECOG-ACRIN Cancer Research Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (39)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

RECRUITING

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045, United States

RECRUITING

UM Sylvester Comprehensive Cancer Center at Aventura

Aventura, Florida, 33180, United States

RECRUITING

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, 33146, United States

RECRUITING

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, 33442, United States

RECRUITING

UM Sylvester Comprehensive Cancer Center at Hollywood

Hollywood, Florida, 33021, United States

RECRUITING

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

RECRUITING

UM Sylvester Comprehensive Cancer Center at Kendall

Miami, Florida, 33176, United States

RECRUITING

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, 33324, United States

RECRUITING

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

RECRUITING

Memorial Hospital East

Shiloh, Illinois, 62269, United States

RECRUITING

IU Health North Hospital

Carmel, Indiana, 46032, United States

RECRUITING

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

RECRUITING

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

RECRUITING

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

RECRUITING

Corewell Health Grand Rapids Hospitals - Butterworth Hospital

Grand Rapids, Michigan, 49503, United States

RECRUITING

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, 63376, United States

RECRUITING

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, 63141, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Siteman Cancer Center-South County

St Louis, Missouri, 63129, United States

RECRUITING

Siteman Cancer Center at Christian Hospital

St Louis, Missouri, 63136, United States

RECRUITING

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester

East White Plains, New York, 10604, United States

RECRUITING

Mount Sinai Hospital

New York, New York, 10029, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

Case Western Reserve University

Cleveland, Ohio, 44106, United States

ACTIVE NOT RECRUITING

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

RECRUITING

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

RECRUITING

West Penn Hospital

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

RECRUITING

Parkland Memorial Hospital

Dallas, Texas, 75235, United States

RECRUITING

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Bevacizumab; Immunoglobulin G; Disulfides; Cetuximab; Floxuridine; 5-fluoro-2'-deoxyuridine; Fluorouracil; dehydroftorafur; Drug Implants; Irinotecan; Leucovorin; Oxaliplatin; Panitumumab; X-Rays; Photons

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Deoxyuridine; Uridine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Uracil; Pyrimidinones; Delayed-Action Preparations; Dosage Forms; Pharmaceutical Preparations; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Elementary Particles; Light; Optical Phenomena; Radiation, Nonionizing

Study Officials

• Michael Lidsky

  ECOG-ACRIN Cancer Research Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2023
• First Posted: May 17, 2023
• Study Start: October 19, 2023
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2034
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

US (39)