Metastatic Colorectal CarcinomaPhase 3NCT05863195
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
A Phase 3 study testing Bevacizumab, Capecitabine and Cetuximab in people with Metastatic Colorectal Carcinoma and Metastatic Malignant Neoplasm in the Liver, run by ECOG-ACRIN Cancer Research Group at 62 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Carcinoma, Metastatic Malignant Neoplasm in the Liver, Stage IV Colorectal Cancer AJCC v8
- What is being tested?
- Bevacizumab, Capecitabine and Cetuximab
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 408 participants
- Where
- 62 sitesUnited States
- Study dates
- 10 Apr 2024to 30 Jun 2029
- Phase
- Phase 3
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
- 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
Show all 40Show fewer
- Patient must have received previous first-line chemotherapy that meets 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 measurable disease
- Patients who have disease progression, in the judgement of the treating multidisciplinary team, are not eligible.
- This requirement does not apply to patients who developed new colorectal liver metastases within 12 months of completing adjuvant systemic therapy for stage II-III colorectal cancer
- 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.
- NOTE: Patients who are deemed technically resectable but simultaneous biologically unresectable are not eligible.
- Patient must undergo multiphase imaging of the chest, abdomen, and pelvis inclusive of CT and/or MRI angiography to confirm acceptable hepatic arterial anatomy for HAI and to rule out extrahepatic disease within 28 days prior to randomization.
- NOTE: If the patient had remote liver-arterial phase imaging greater than 4 weeks from randomization, then only a single phase (portal venous) intravenous contrasted staging CT and/or MRI of the chest/abdomen/pelvis is required.
- 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.
- 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 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.
- Leukocytes >= 3,000/mcL (obtained =< 28 days prior to protocol randomization)
- Absolute neutrophil count (ANC) >= 1,500/mcL (obtained =< 28 days prior to protocol randomization)
- Platelets >= 100,000/mcL (obtained =< 28 days prior to protocol randomization)
- Total Bilirubin =< 1.5 mg/dL (obtained =< 28 days prior to protocol randomization)
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) =< 3.0 x institutional upper limit of normal (ULN) (obtained =< 28 days prior to protocol randomization)
- Creatinine =< 1.5 x institutional ULN OR creatinine clearance >= 50 mL/min calculated by the Cockcroft-Gault method (obtained =< 28 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
Who cannot join
None listed.
Trial locations and contacts
62 sites in 1 country. Contact the study team or a site near you to ask about taking part.
62 sites in 1 country
United States62 sites, 54 recruiting
- Recruiting
Lehigh Valley Hospital-Cedar Crest
Allentown, Pennsylvania, 18103
Site Public Contact, 610-402-9543, Morgan_M.Horton@lvhn.org
Tareq Al baghdadi
- Recruiting
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109
Site Public Contact, 800-865-1125, CancerAnswerLine@med.umich.edu
Benjamin D. Ferguson
- Recruiting
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
Site Public Contact, 404-778-1868
Olumide B. Gbolahan
- Recruiting
Emory Saint Joseph's Hospital
Atlanta, Georgia, 30342
Site Public Contact, 404-851-7115
Olumide B. Gbolahan
- Recruiting
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045
Site Public Contact, 720-848-0650
Alexis D. Leal
- Recruiting
UM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida, 33180
Site Public Contact, 954-461-2180
Jashodeep Datta
- Recruiting
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920
Site Public Contact, 212-639-7592
Andrea Cercek
- Withdrawn
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
- Recruiting
Roswell Park Cancer Institute
Buffalo, New York, 14263
Site Public Contact, 800-767-9355, askroswell@roswellpark.org
Anuradha Krishnamurthy
- Recruiting
IU Health North Hospital
Carmel, Indiana, 46032
Site Public Contact, 317-278-5632, iutrials@iu.edu
Anita Turk
- Recruiting
Northwestern University
Chicago, Illinois, 60611
Site Public Contact, 312-695-1301, cancer@northwestern.edu
Shishir K. Maithel
- Recruiting
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Site Public Contact, 773-702-8222, cancerclinicaltrials@bsd.uchicago.edu
Ryan Merkow
- Recruiting
Northwestern Medicine Cancer Center Old Irving Park
Chicago, Illinois, 60641
Site Public Contact, nctnprogram_rhlccc@northwestern.edu
Shishir K. Maithel
- Withdrawn
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376
- Active, not recruiting
Case Western Reserve University
Cleveland, Ohio, 44106
- Recruiting
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Site Public Contact, 800-293-5066, Jamesline@osumc.edu
Alex B. Blair
- Recruiting
Memorial Sloan Kettering Commack
Commack, New York, 11725
Site Public Contact, 212-639-7592
Andrea Cercek
- Recruiting
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146
Site Public Contact, 305-243-2647
Jashodeep Datta
- Withdrawn
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141
- Recruiting
Parkland Memorial Hospital
Dallas, Texas, 75235
Site Public Contact, 214-590-5582, canceranswerline@UTSouthwestern.edu
Adam C. Yopp
- Recruiting
UT Southwestern Simmons Cancer Center - RedBird
Dallas, Texas, 75237
Site Public Contact, 214-648-7097, canceranswerline@utsouthwestern.edu
Adam C. Yopp
- Recruiting
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Site Public Contact, 214-648-7097, canceranswerline@UTSouthwestern.edu
Adam C. Yopp
- Recruiting
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442
Site Public Contact, 305-243-2647
Jashodeep Datta
- Recruiting
Duke University Medical Center
Durham, North Carolina, 27710
Site Public Contact, 888-275-3853
Hope E. Uronis
- Recruiting
Memorial Sloan Kettering Westchester
East White Plains, New York, 10604
Site Public Contact, 212-639-7592
Andrea Cercek
- Recruiting
Saint Vincent Hospital
Erie, Pennsylvania, 16544
Site Public Contact, 814-452-5000
Patrick L. Wagner
- Recruiting
UT Southwestern/Simmons Cancer Center-Fort Worth
Fort Worth, Texas, 76104
Site Public Contact, 214-648-7097, canceranswerline@UTSouthwestern.edu
Adam C. Yopp
- Recruiting
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234
Site Public Contact, 602-747-9738
Rajesh Ramanathan
- Recruiting
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
Grand Rapids, Michigan, 49503
Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org
Kathleen Y. Butler
- Recruiting
UM Sylvester Comprehensive Cancer Center at Hollywood
Hollywood, Florida, 33021
Site Public Contact, 305-243-2647
Jashodeep Datta
- Recruiting
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
Site Public Contact, 317-278-5632, iutrials@iu.edu
Anita Turk
- Recruiting
Jefferson Hospital
Jefferson Hills, Pennsylvania, 15025
Site Public Contact, 412-359-3043, ddefazio@wpahs.org
Patrick L. Wagner
- Recruiting
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Site Public Contact, 859-257-3379
Michael J. Cavnar
- Recruiting
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718
Site Public Contact, 800-622-8922, clinicaltrials@cancer.wisc.edu
Patrick Varley
- Recruiting
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
Site Public Contact, 800-622-8922, clinicaltrials@cancer.wisc.edu
Patrick Varley
- Recruiting
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Site Public Contact, 305-243-2647
Jashodeep Datta
- Recruiting
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, 33176
Site Public Contact, 305-243-2647
Jashodeep Datta
- Recruiting
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748
Site Public Contact, 212-639-7592
Andrea Cercek
- Recruiting
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455
Site Public Contact, 612-624-2620
Ajay Prakash
- Recruiting
Forbes Hospital
Monroeville, Pennsylvania, 15146
Site Public Contact, 412-858-7746
Patrick L. Wagner
- Recruiting
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645
Site Public Contact, 212-639-7592
Andrea Cercek
- Recruiting
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Site Public Contact, 800-811-8480
Chandrasekhar Padmanabhan
- Recruiting
Mount Sinai Hospital
New York, New York, 10029
Site Public Contact, 212-824-7309, CCTO@mssm.edu
James O. Park
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Site Public Contact, 212-639-7592
Andrea Cercek
- Recruiting
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Site Public Contact, 215-728-4790
Vanessa Wookey
- Recruiting
Banner-University Medical Center Phoenix
Phoenix, Arizona, 85006
Site Public Contact, BannerResearch@bannerhealth.com
Rajesh Ramanathan
- Recruiting
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
Site Public Contact, 877-284-2000
Patrick L. Wagner
- Recruiting
West Penn Hospital
Pittsburgh, Pennsylvania, 15224
Site Public Contact, 412-578-5000
Patrick L. Wagner
- Recruiting
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324
Site Public Contact, 305-243-2647
Jashodeep Datta
- Recruiting
Oregon Health and Science University
Portland, Oregon, 97239
Site Public Contact, 503-494-1080, trials@ohsu.edu
Skye C. Mayo
- Recruiting
Duke Cancer Center Raleigh
Raleigh, North Carolina, 27609
Site Public Contact, NCTNStudyTeam@dm.duke.edu
Hope E. Uronis
- Recruiting
UT Southwestern Clinical Center at Richardson/Plano
Richardson, Texas, 75080
Site Public Contact, 972-669-7044, Suzanne.cole@utsouthwestern.edu
Adam C. Yopp
- Recruiting
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Site Public Contact, 855-776-0015
Cornelius A. Thiels
- Withdrawn
Memorial Hospital East
Shiloh, Illinois, 62269
- Withdrawn
Washington University School of Medicine
St Louis, Missouri, 63110
- Withdrawn
Siteman Cancer Center-South County
St Louis, Missouri, 63129
- Withdrawn
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136
- Recruiting
Banner Boswell Medical Center
Sun City, Arizona, 85351
Site Public Contact, 480-440-7458, BMDACCResearch@bannerhealth.com
Rajesh Ramanathan
- Recruiting
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553
Site Public Contact, 212-639-7592
Andrea Cercek
- Recruiting
Wexford Health and Wellness Pavilion
Wexford, Pennsylvania, 15090
Site Public Contact, Dawnmarie.DeFazio@ahn.org
Patrick L. Wagner
- Recruiting
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Site Public Contact, 336-713-6771
Perry Shen
- Recruiting
Saint Elizabeth Youngstown Hospital
Youngstown, Ohio, 44501
Site Public Contact, 937-528-2900, clinical.trials@daytonncorp.org
Howard M. Gross
About this study
Official title: A Randomized Phase III Study of Systemic Therapy With or Without Hepatic Arterial Infusion for Unresectable Colorectal Liver Metastases: The PUMP Trial
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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.
- 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 within 6 weeks of randomization, followed by single photon emission computed tomography/computed tomography (SPECT/CT) on study. Patients then receive floxuridine via the HAI pump within 12 weeks of randomization on study. Patients also receive one of the following standard chemotherapy regimens per the treating physician within 16 weeks of randomization: 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 days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may have leucovorin omitted from their regimen per institutional standards. Patients also undergo CT and/or magnetic resonance imaging (MRI) scans throughout the trial.
ARM B: Patients receive one of the following standard chemotherapy regimens per the treating physician within 6 weeks of randomization: FOLFOXIRI (fluorouracil IV, oxaliplatin IV, irinotecan IV, and leucovorin IV), FOLFOX IV, FOLFIRI IV, or OX/IRI IV with or without cetuximab IV, panitumumab IV, and/or bevacizumab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may receive capecitabine orally (PO) in substitution for fluorouracil at the discretion of the investigator and may have leucovorin omitted from their regimen per institutional standards. Patients also undergo CT and/or MRI scans throughout the trial.
After completion of treatment, patients follow up every 3 months for 2 years and then every 6 months for an additional 3 years.
- Conditions
- Metastatic Colorectal Carcinoma, Metastatic Malignant Neoplasm in the Liver, Stage IV Colorectal Cancer AJCC v8, Unresectable Colorectal Carcinoma
- Being tested
- Bevacizumab, Capecitabine, Cetuximab, Computed Tomography, Floxuridine
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabBiological
Also called ABP 215, ABP-215, ABP215, Alymsys
Given IV
CapecitabineDrug
Also called Ro 09-1978/000, Xeloda
Given PO
CetuximabBiological
Also called C 225, C-225, C225, Cetuxa
Given IV
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo SPECT/CT and/or CT
FloxuridineDrug
Also called 2'-Deoxy-5-fluorouridine, 5-Fluoro-2'-deoxyuridine, 5-Fluorodeoxyuridine, 5-Fluorouracil deoxyriboside
Given via HAI pump
FluorouracilDrug
Also called 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
Given IV
ImplantationProcedure or surgery
Undergo surgery to place the HAI pump
Intrahepatic Infusion ProcedureProcedure or surgery
Also called HAI, Hepatic Arterial Infusion, Hepatic Artery Infusion, IHI
Undergo HAI
IrinotecanDrug
Given IV
LeucovorinDrug
Also called Folinic acid
Given IV
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
OxaliplatinDrug
Also called 1-OHP, Ai Heng, Aiheng, Dacotin
Given IV
PanitumumabBiological
Also called ABX-EGF, ABX-EGF Monoclonal Antibody, ABX-EGF, Clone E7.6.3, E7.6.3
Given IV
Single Photon Emission Computed TomographyProcedure or surgery
Also called Medical Imaging, Single Photon Emission Computed Tomography, Single Photon Emission Tomography, Single-Photon Emission Computed, single-photon emission computed tomography
Undergo SPECT/CT
| Study group | Role | What they receive |
|---|---|---|
| Arm A (HAI, floxuridine, standard chemotherapy) | Experimental | Patients undergo surgery to place the HAI pump within 6 weeks of randomization, followed by single SPECT/CT on study. Patients then receive floxuridine via the HAI pump within 12 weeks of randomization on study. Patients also receive one of the following standard chemotherapy regimens per the treating physician within 16 weeks of randomization: FOLFOX IV, FOLFIRI IV, or OX/IRI IV with or without cetuximab IV and/or panitumumab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may have leucovorin omitted from their regimen per institutional standards. Patients also undergo CT and/or MRI scans throughout the trial. Receives: Biological: Cetuximab; Procedure: Computed Tomography; Drug: Floxuridine; Drug: Fluorouracil; Procedure: Implantation; Procedure: Intrahepatic Infusion Procedure; Drug: Irinotecan; Drug: Leucovorin; Procedure: Magnetic Resonance Imaging; 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 within 6 weeks of randomization: FOLFOXIRI IV, FOLFOX IV, FOLFIRI IV, or OX/IRI IV with or without cetuximab IV, panitumumab IV, and/or bevacizumab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may receive capecitabine PO in substitution for fluorouracil at the discretion of the investigator and may have leucovorin omitted from their regimen per institutional standards. Patients also undergo CT and/or MRI scans throughout the trial. Receives: Biological: Bevacizumab; Drug: Capecitabine; Biological: Cetuximab; Procedure: Computed Tomography; Drug: Fluorouracil; Drug: Irinotecan; Drug: Leucovorin; Procedure: Magnetic Resonance Imaging; Drug: Oxaliplatin; Biological: Panitumumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From randomization to death from any cause, assessed up to 5 years
Secondary outcomes (7)
Progression free survival (PFS)
Patients still living without disease progression will be censored at the date of last disease assessment. Disease progression will be based on findings from surveillance cross-sectional imaging of the chest/abdomen/pelvis every 3 months after randomization, defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will be analyzed similarly to OS, but with and without stratification for sensitivity.
Measured: From randomization to first observed disease progression at any site, or death from any cause, assessed up to 5 years
Hepatic PFS
Patients still living without hepatic disease progression will be censored at the date of last disease assessment. Hepatic disease progression will be based on findings from surveillance cross-sectional imaging of the chest/abdomen/pelvis every 3 months after randomization, defined by RECIST 1.1.
Measured: From randomization to first observed disease progression in the liver, or death from any cause, assessed up to 5 years
Extrahepatic-PFS
Patients still living without extrahepatic disease progression will be censored at the date of last disease assessment. Extrahepatic disease progression will be based on findings from surveillance cross-sectional imaging of the chest/abdomen/pelvis every 3 months after randomization, defined by RECIST 1.1.
Measured: From randomization to first observed disease progression outside of the liver, or death from any cause, assessed up to 5 years
Objective response rate
Will assess hepatic disease burden specifically. Defined as the proportion of patients achieving complete or partial response by RECIST 1.1. Response will be based on surveillance cross-sectional imaging of the chest/abdomen/pelvis every 3 months (+/- 2 weeks) from randomization. Arms will be compared via a Pearson chi-square test. All rates will be reported with exact binomial 95% confidence intervals.
Measured: Up to 5 years
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. All rates will be reported with exact binomial 95% confidence intervals.
Measured: Up to 5 years
Intra-operative ineligibility rate
Defined as the proportion of patients intended to receive hepatic arterial infusion that do not undergo pump implantation due to intraoperative detection of occult extrahepatic disease or unsuitable hepatic arterial anatomy. All rates will be reported with exact binomial 95% confidence intervals.
Measured: Up to 5 years
Incidence of adverse events
Defined according to the Common Terminology Criteria for Adverse Events.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2023
- Study start10 Apr 2024
- Primary completion30 Jun 2029 (estimated)
- Study completion30 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal CarcinomaStudies of the same condition, open and under way.
- More trials run by ECOG-ACRIN Cancer Research GroupThe 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
- 408 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ECOG-ACRIN Cancer Research Group
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Michael Lidsky, Principal investigator, ECOG-ACRIN Cancer Research Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05863195
- Sponsor's protocol ID
- EA2222
- Other IDs
- NCI-2023-02357, EA2222, EA2222, U10CA180820
- Status last verified
- Sep 2026
- First submitted
- 9 May 2023
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No