Test af pumpekemoterapi ud over standardbehandlingskemoterapi versus standardbehandlingskemoterapi alene for patienter med ikke-operable kolorektale levermetastaser: PUMP-forsøget
Et randomiseret fase III-studie af systemisk terapi med eller uden hepatisk arteriel infusion for ikke-operable kolorektale levermetastaser: PUMP-forsøget
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.
Studieoversigt
Status
Status
Betingelser
Betingelser
Intervention / Behandling
Intervention / Behandling
- Biologisk: Bevacizumab
- Medicin: Fluorouracil
- Procedure: Magnetic Resonance Imaging
- Medicin: Capecitabine
- Biologisk: Panitumumab
- Medicin: Oxaliplatin
- Medicin: Leucovorin
- Biologisk: Cetuximab
- Medicin: Irinotecan
- Medicin: Floxuridine
- Procedure: Computed Tomography
- Procedure: Implantation
- Procedure: Intrahepatic Infusion Procedure
- Procedure: Single Photon Emission Computed Tomography
Detaljeret beskrivelse
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 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.
Undersøgelsestype
Undersøgelsestype
Tilmelding (Anslået)
Tilmelding
Fase
Fase
- Fase 3
Kontakter og lokationer
Studiesteder
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Alabama
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Birmingham, Alabama, Forenede Stater, 35233
- Trukket tilbage
- University of Alabama at Birmingham Cancer Center
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Arizona
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Gilbert, Arizona, Forenede Stater, 85234
- Rekruttering
- Banner MD Anderson Cancer Center
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Kontakt:
- Site Public Contact
- Telefonnummer: 602-747-9738
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Ledende efterforsker:
- Rajesh Ramanathan
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Phoenix, Arizona, Forenede Stater, 85006
- Rekruttering
- Banner-University Medical Center Phoenix
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Kontakt:
- Site Public Contact
- E-mail: BannerResearch@bannerhealth.com
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Ledende efterforsker:
- Rajesh Ramanathan
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Sun City, Arizona, Forenede Stater, 85351
- Rekruttering
- Banner Boswell Medical Center
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Kontakt:
- Site Public Contact
- Telefonnummer: 480-440-7458
- E-mail: BMDACCResearch@bannerhealth.com
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Ledende efterforsker:
- Rajesh Ramanathan
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Colorado
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Aurora, Colorado, Forenede Stater, 80045
- Rekruttering
- UCHealth University of Colorado Hospital
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Kontakt:
- Site Public Contact
- Telefonnummer: 720-848-0650
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Ledende efterforsker:
- Alexis D. Leal
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Florida
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Aventura, Florida, Forenede Stater, 33180
- Rekruttering
- UM Sylvester Comprehensive Cancer Center at Aventura
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Ledende efterforsker:
- Jashodeep Datta
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Kontakt:
- Site Public Contact
- Telefonnummer: 954-461-2180
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Coral Gables, Florida, Forenede Stater, 33146
- Rekruttering
- UM Sylvester Comprehensive Cancer Center at Coral Gables
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Ledende efterforsker:
- Jashodeep Datta
-
Kontakt:
- Site Public Contact
- Telefonnummer: 305-243-2647
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Deerfield Beach, Florida, Forenede Stater, 33442
- Rekruttering
- UM Sylvester Comprehensive Cancer Center at Deerfield Beach
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Ledende efterforsker:
- Jashodeep Datta
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Kontakt:
- Site Public Contact
- Telefonnummer: 305-243-2647
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Hollywood, Florida, Forenede Stater, 33021
- Rekruttering
- UM Sylvester Comprehensive Cancer Center at Hollywood
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Ledende efterforsker:
- Jashodeep Datta
-
Kontakt:
- Site Public Contact
- Telefonnummer: 305-243-2647
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Miami, Florida, Forenede Stater, 33136
- Rekruttering
- University of Miami Miller School of Medicine-Sylvester Cancer Center
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Ledende efterforsker:
- Jashodeep Datta
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Kontakt:
- Site Public Contact
- Telefonnummer: 305-243-2647
-
Miami, Florida, Forenede Stater, 33176
- Rekruttering
- UM Sylvester Comprehensive Cancer Center at Kendall
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Ledende efterforsker:
- Jashodeep Datta
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Kontakt:
- Site Public Contact
- Telefonnummer: 305-243-2647
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Plantation, Florida, Forenede Stater, 33324
- Rekruttering
- UM Sylvester Comprehensive Cancer Center at Plantation
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Ledende efterforsker:
- Jashodeep Datta
-
Kontakt:
- Site Public Contact
- Telefonnummer: 305-243-2647
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Georgia
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Atlanta, Georgia, Forenede Stater, 30322
- Rekruttering
- Emory University Hospital/Winship Cancer Institute
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Kontakt:
- Site Public Contact
- Telefonnummer: 404-778-1868
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Ledende efterforsker:
- Olumide B. Gbolahan
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Atlanta, Georgia, Forenede Stater, 30342
- Rekruttering
- Emory Saint Joseph's Hospital
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Ledende efterforsker:
- Olumide B. Gbolahan
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Kontakt:
- Site Public Contact
- Telefonnummer: 404-851-7115
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Illinois
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Chicago, Illinois, Forenede Stater, 60637
- Rekruttering
- University of Chicago Comprehensive Cancer Center
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Kontakt:
- Site Public Contact
- Telefonnummer: 773-702-8222
- E-mail: cancerclinicaltrials@bsd.uchicago.edu
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Ledende efterforsker:
- Ryan Merkow
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Chicago, Illinois, Forenede Stater, 60611
- Rekruttering
- Northwestern University
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Kontakt:
- Site Public Contact
- Telefonnummer: 312-695-1301
- E-mail: cancer@northwestern.edu
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Ledende efterforsker:
- Shishir K. Maithel
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Chicago, Illinois, Forenede Stater, 60641
- Rekruttering
- Northwestern Medicine Cancer Center Old Irving Park
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Ledende efterforsker:
- Shishir K. Maithel
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Kontakt:
- Site Public Contact
- E-mail: nctnprogram_rhlccc@northwestern.edu
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Shiloh, Illinois, Forenede Stater, 62269
- Trukket tilbage
- Memorial Hospital East
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Indiana
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Carmel, Indiana, Forenede Stater, 46032
- Rekruttering
- IU Health North Hospital
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Kontakt:
- Site Public Contact
- Telefonnummer: 317-278-5632
- E-mail: iutrials@iu.edu
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Ledende efterforsker:
- Anita Turk
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Indianapolis, Indiana, Forenede Stater, 46202
- Rekruttering
- Indiana University/Melvin and Bren Simon Cancer Center
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Kontakt:
- Site Public Contact
- Telefonnummer: 317-278-5632
- E-mail: iutrials@iu.edu
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Ledende efterforsker:
- Anita Turk
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Kentucky
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Lexington, Kentucky, Forenede Stater, 40536
- Rekruttering
- University of Kentucky/Markey Cancer Center
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Ledende efterforsker:
- Michael J. Cavnar
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Kontakt:
- Site Public Contact
- Telefonnummer: 859-257-3379
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Michigan
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Ann Arbor, Michigan, Forenede Stater, 48109
- Rekruttering
- University of Michigan Rogel Cancer Center
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Ledende efterforsker:
- Benjamin D. Ferguson
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Kontakt:
- Site Public Contact
- Telefonnummer: 800-865-1125
- E-mail: CancerAnswerLine@med.umich.edu
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Grand Rapids, Michigan, Forenede Stater, 49503
- Rekruttering
- Corewell Health Grand Rapids Hospitals - Butterworth Hospital
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Kontakt:
- Site Public Contact
- Telefonnummer: 616-391-1230
- E-mail: crcwm-regulatory@crcwm.org
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Ledende efterforsker:
- Kathleen Y. Butler
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Minnesota
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Minneapolis, Minnesota, Forenede Stater, 55455
- Rekruttering
- University of Minnesota/Masonic Cancer Center
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Kontakt:
- Site Public Contact
- Telefonnummer: 612-624-2620
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Ledende efterforsker:
- Ajay Prakash
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Rochester, Minnesota, Forenede Stater, 55905
- Rekruttering
- Mayo Clinic in Rochester
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Kontakt:
- Site Public Contact
- Telefonnummer: 855-776-0015
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Ledende efterforsker:
- Cornelius A. Thiels
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Missouri
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City of Saint Peters, Missouri, Forenede Stater, 63376
- Trukket tilbage
- Siteman Cancer Center at Saint Peters Hospital
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Creve Coeur, Missouri, Forenede Stater, 63141
- Trukket tilbage
- Siteman Cancer Center at West County Hospital
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St Louis, Missouri, Forenede Stater, 63110
- Trukket tilbage
- Washington University School of Medicine
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St Louis, Missouri, Forenede Stater, 63129
- Trukket tilbage
- Siteman Cancer Center-South County
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St Louis, Missouri, Forenede Stater, 63136
- Trukket tilbage
- Siteman Cancer Center at Christian Hospital
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New Jersey
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Basking Ridge, New Jersey, Forenede Stater, 07920
- Rekruttering
- Memorial Sloan Kettering Basking Ridge
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Kontakt:
- Site Public Contact
- Telefonnummer: 212-639-7592
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Ledende efterforsker:
- Andrea Cercek
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Middletown, New Jersey, Forenede Stater, 07748
- Rekruttering
- Memorial Sloan Kettering Monmouth
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Kontakt:
- Site Public Contact
- Telefonnummer: 212-639-7592
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Ledende efterforsker:
- Andrea Cercek
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Montvale, New Jersey, Forenede Stater, 07645
- Rekruttering
- Memorial Sloan Kettering Bergen
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Kontakt:
- Site Public Contact
- Telefonnummer: 212-639-7592
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Ledende efterforsker:
- Andrea Cercek
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New York
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Buffalo, New York, Forenede Stater, 14263
- Rekruttering
- Roswell Park Cancer Institute
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Ledende efterforsker:
- Anuradha Krishnamurthy
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Kontakt:
- Site Public Contact
- Telefonnummer: 800-767-9355
- E-mail: askroswell@roswellpark.org
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Commack, New York, Forenede Stater, 11725
- Rekruttering
- Memorial Sloan Kettering Commack
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Kontakt:
- Site Public Contact
- Telefonnummer: 212-639-7592
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Ledende efterforsker:
- Andrea Cercek
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East White Plains, New York, Forenede Stater, 10604
- Rekruttering
- Memorial Sloan Kettering Westchester
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Kontakt:
- Site Public Contact
- Telefonnummer: 212-639-7592
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Ledende efterforsker:
- Andrea Cercek
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New York, New York, Forenede Stater, 10065
- Rekruttering
- Memorial Sloan Kettering Cancer Center
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Kontakt:
- Site Public Contact
- Telefonnummer: 212-639-7592
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Ledende efterforsker:
- Andrea Cercek
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New York, New York, Forenede Stater, 10029
- Rekruttering
- Mount Sinai Hospital
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Kontakt:
- Site Public Contact
- Telefonnummer: 212-824-7309
- E-mail: CCTO@mssm.edu
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Ledende efterforsker:
- James O. Park
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Uniondale, New York, Forenede Stater, 11553
- Rekruttering
- Memorial Sloan Kettering Nassau
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Kontakt:
- Site Public Contact
- Telefonnummer: 212-639-7592
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Ledende efterforsker:
- Andrea Cercek
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North Carolina
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Durham, North Carolina, Forenede Stater, 27710
- Rekruttering
- Duke University Medical Center
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Kontakt:
- Site Public Contact
- Telefonnummer: 888-275-3853
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Ledende efterforsker:
- Hope E. Uronis
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Raleigh, North Carolina, Forenede Stater, 27609
- Rekruttering
- Duke Cancer Center Raleigh
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Ledende efterforsker:
- Hope E. Uronis
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Kontakt:
- Site Public Contact
- E-mail: NCTNStudyTeam@dm.duke.edu
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Winston-Salem, North Carolina, Forenede Stater, 27157
- Rekruttering
- Wake Forest University Health Sciences
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Ledende efterforsker:
- Perry Shen
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Kontakt:
- Site Public Contact
- Telefonnummer: 336-713-6771
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Ohio
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Cleveland, Ohio, Forenede Stater, 44106
- Aktiv, ikke rekrutterende
- Case Western Reserve University
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Columbus, Ohio, Forenede Stater, 43210
- Rekruttering
- Ohio State University Comprehensive Cancer Center
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Kontakt:
- Site Public Contact
- Telefonnummer: 800-293-5066
- E-mail: Jamesline@osumc.edu
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Ledende efterforsker:
- Alex B. Blair
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Youngstown, Ohio, Forenede Stater, 44501
- Rekruttering
- Saint Elizabeth Youngstown Hospital
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Kontakt:
- Site Public Contact
- Telefonnummer: 937-528-2900
- E-mail: clinical.trials@daytonncorp.org
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Ledende efterforsker:
- Howard M. Gross
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Oregon
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Portland, Oregon, Forenede Stater, 97239
- Rekruttering
- Oregon Health and Science University
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Kontakt:
- Site Public Contact
- Telefonnummer: 503-494-1080
- E-mail: trials@ohsu.edu
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Ledende efterforsker:
- Skye C. Mayo
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Pennsylvania
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Allentown, Pennsylvania, Forenede Stater, 18103
- Rekruttering
- Lehigh Valley Hospital-Cedar Crest
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Kontakt:
- Site Public Contact
- Telefonnummer: 610-402-9543
- E-mail: Morgan_M.Horton@lvhn.org
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Ledende efterforsker:
- Tareq Al baghdadi
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Erie, Pennsylvania, Forenede Stater, 16544
- Rekruttering
- Saint Vincent Hospital
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Kontakt:
- Site Public Contact
- Telefonnummer: 814-452-5000
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Ledende efterforsker:
- Patrick L. Wagner
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Jefferson Hills, Pennsylvania, Forenede Stater, 15025
- Rekruttering
- Jefferson Hospital
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Kontakt:
- Site Public Contact
- Telefonnummer: 412-359-3043
- E-mail: ddefazio@wpahs.org
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Ledende efterforsker:
- Patrick L. Wagner
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Monroeville, Pennsylvania, Forenede Stater, 15146
- Rekruttering
- Forbes Hospital
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Kontakt:
- Site Public Contact
- Telefonnummer: 412-858-7746
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Ledende efterforsker:
- Patrick L. Wagner
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Philadelphia, Pennsylvania, Forenede Stater, 19111
- Rekruttering
- Fox Chase Cancer Center
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Kontakt:
- Site Public Contact
- Telefonnummer: 215-728-4790
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Ledende efterforsker:
- Vanessa Wookey
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Pittsburgh, Pennsylvania, Forenede Stater, 15224
- Rekruttering
- West Penn Hospital
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Kontakt:
- Site Public Contact
- Telefonnummer: 412-578-5000
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Ledende efterforsker:
- Patrick L. Wagner
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Pittsburgh, Pennsylvania, Forenede Stater, 15212
- Rekruttering
- Allegheny General Hospital
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Kontakt:
- Site Public Contact
- Telefonnummer: 877-284-2000
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Ledende efterforsker:
- Patrick L. Wagner
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Wexford, Pennsylvania, Forenede Stater, 15090
- Rekruttering
- Wexford Health and Wellness Pavilion
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Kontakt:
- Site Public Contact
- E-mail: Dawnmarie.DeFazio@ahn.org
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Ledende efterforsker:
- Patrick L. Wagner
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Tennessee
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Nashville, Tennessee, Forenede Stater, 37232
- Rekruttering
- Vanderbilt University/Ingram Cancer Center
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Kontakt:
- Site Public Contact
- Telefonnummer: 800-811-8480
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Ledende efterforsker:
- Chandrasekhar Padmanabhan
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Texas
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Dallas, Texas, Forenede Stater, 75390
- Rekruttering
- UT Southwestern/Simmons Cancer Center-Dallas
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Kontakt:
- Site Public Contact
- Telefonnummer: 214-648-7097
- E-mail: canceranswerline@UTSouthwestern.edu
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Ledende efterforsker:
- Adam C. Yopp
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Dallas, Texas, Forenede Stater, 75235
- Rekruttering
- Parkland Memorial Hospital
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Kontakt:
- Site Public Contact
- Telefonnummer: 214-590-5582
- E-mail: canceranswerline@UTSouthwestern.edu
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Ledende efterforsker:
- Adam C. Yopp
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Dallas, Texas, Forenede Stater, 75237
- Rekruttering
- UT Southwestern Simmons Cancer Center - RedBird
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Ledende efterforsker:
- Adam C. Yopp
-
Kontakt:
- Site Public Contact
- Telefonnummer: 214-648-7097
- E-mail: canceranswerline@utsouthwestern.edu
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Fort Worth, Texas, Forenede Stater, 76104
- Rekruttering
- UT Southwestern/Simmons Cancer Center-Fort Worth
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Kontakt:
- Site Public Contact
- Telefonnummer: 214-648-7097
- E-mail: canceranswerline@UTSouthwestern.edu
-
Ledende efterforsker:
- Adam C. Yopp
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Richardson, Texas, Forenede Stater, 75080
- Rekruttering
- UT Southwestern Clinical Center at Richardson/Plano
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Kontakt:
- Site Public Contact
- Telefonnummer: 972-669-7044
- E-mail: Suzanne.cole@utsouthwestern.edu
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Ledende efterforsker:
- Adam C. Yopp
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Wisconsin
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Madison, Wisconsin, Forenede Stater, 53792
- Rekruttering
- University of Wisconsin Carbone Cancer Center - University Hospital
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Kontakt:
- Site Public Contact
- Telefonnummer: 800-622-8922
- E-mail: clinicaltrials@cancer.wisc.edu
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Ledende efterforsker:
- Patrick Varley
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Madison, Wisconsin, Forenede Stater, 53718
- Rekruttering
- University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
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Kontakt:
- Site Public Contact
- Telefonnummer: 800-622-8922
- E-mail: clinicaltrials@cancer.wisc.edu
-
Ledende efterforsker:
- Patrick Varley
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Deltagelseskriterier
Berettigelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
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Patient must be >= 18 years of age
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Patient must have confirmed unresectable liver confined metastatic colorectal cancer (CRC).
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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.
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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.
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Patient's primary tumor may be in place
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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
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Patient must have measurable disease
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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
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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.
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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.
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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.
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Patient must not have a liver tumor burden exceeding 70% of total liver volume.
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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).
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Patient must not have had prior trans-arterial bland embolization, chemoembolization (TACE) or radioembolization (TARE).
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Patient must not have had prior treatment with HAI/floxuridine (FUDR)
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Patient must not have microsatellite instability-high (MSI-H) colorectal cancer.
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Patient must not have CRLM that could be resected with 2-stage hepatectomy, including associating liver partition and portal vein ligation (ALPPS).
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Patient must not have an active infection, serious or non-healing active wound, ulcer, or bone fracture.
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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.
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Patient must not have cirrhosis and/or clinical or radiographic evidence of portal hypertension
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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)
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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.
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Leukocytes >= 3,000/mcL (obtained =< 28 days prior to protocol randomization)
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Absolute neutrophil count (ANC) >= 1,500/mcL (obtained =< 28 days prior to protocol randomization)
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Platelets >= 100,000/mcL (obtained =< 28 days prior to protocol randomization)
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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
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Antal våben
Våben og indgreb
Deltagergruppe / ArmDeltagergruppe / Arm |
Intervention / BehandlingIntervention / Behandling |
|---|---|
|
Eksperimentel: Arm A (HAI, floxuridine, standard chemotherapy)
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. |
Given IV
Andre navne:
Undergo MRI
Andre navne:
Given IV
Andre navne:
Given IV
Andre navne:
Given IV
Andre navne:
Given IV
Andre navne:
Given IV Given via HAI pump
Andre navne:
Undergo SPECT/CT and/or CT
Andre navne:
Undergo surgery to place the HAI pump Undergo HAI
Andre navne:
Undergo SPECT/CT
Andre navne:
|
|
Aktiv komparator: Arm B (standard chemotherapy)
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. |
Given IV
Andre navne:
Given IV
Andre navne:
Undergo MRI
Andre navne:
Given PO
Andre navne:
Given IV
Andre navne:
Given IV
Andre navne:
Given IV
Andre navne:
Given IV
Andre navne:
Given IV Undergo SPECT/CT and/or CT
Andre navne:
|
Hvad måler undersøgelsen?
Primære resultatmål
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Overall survival (OS)
Tidsramme: From randomization to death from any cause, assessed up to 5 years
|
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
|
Sekundære resultatmål
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Progression free survival (PFS)
Tidsramme: From randomization to first observed disease progression at any site, or death from any cause, assessed up to 5 years
|
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. |
From randomization to first observed disease progression at any site, or death from any cause, assessed up to 5 years
|
|
Hepatic PFS
Tidsramme: From randomization to first observed disease progression in the liver, or death from any cause, assessed up to 5 years
|
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. |
From randomization to first observed disease progression in the liver, or death from any cause, assessed up to 5 years
|
|
Extrahepatic-PFS
Tidsramme: From randomization to first observed disease progression outside of the liver, or death from any cause, assessed up to 5 years
|
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. |
From randomization to first observed disease progression outside of the liver, or death from any cause, assessed up to 5 years
|
|
Objective response rate
Tidsramme: Up to 5 years
|
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. |
Up to 5 years
|
|
Rate of conversion to resectable disease
Tidsramme: Up to 5 years
|
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. |
Up to 5 years
|
|
Intra-operative ineligibility rate
Tidsramme: Up to 5 years
|
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. |
Up to 5 years
|
|
Incidence of adverse events
Tidsramme: Up to 5 years
|
Defined according to the Common Terminology Criteria for Adverse Events. |
Up to 5 years
|
Samarbejdspartnere og efterforskere
Sponsor
Sponsor
Efterforskere
Efterforskere
- Ledende efterforsker: Michael Lidsky, ECOG-ACRIN Cancer Research Group
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Studiestart
Primær færdiggørelse (Anslået)
Primær færdiggørelse
Studieafslutning (Anslået)
Studieafslutning
Datoer for studieregistrering
Først indsendt
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Først opslået
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering sendt
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Neoplasmer efter sted
- Neoplasmer
- Tarmsygdomme
- Gastrointestinale neoplasmer
- Neoplasmer i fordøjelsessystemet
- Sygdomme i fordøjelsessystemet
- Gastrointestinale sygdomme
- Intestinale neoplasmer
- Endetarmssygdomme
- Tyktarmssygdomme
- Kolorektale neoplasmer
- Aminosyrer, peptider og proteiner
- Proteiner
- Svovlforbindelser
- Organiske kemikalier
- Heterocykliske forbindelser, 1-ring
- Heterocykliske forbindelser
- Heterocykliske forbindelser, 2-ring
- Heterocykliske forbindelser, smeltet ring
- Farmaceutiske præparater
- Undersøgelsesteknikker
- Doseringsformer
- Nukleinsyrer, nukleotider og nukleosider
- Fysiske fænomener
- Camptothecin
- Alkaloider
- Enzymer og coenzymer
- Antistoffer, monoklonal, humaniseret
- Antistoffer, monoklonal
- Antistoffer
- Immunoglobuliner
- Immunoproteiner
- Blodproteiner
- Serum globuliner
- Globuliner
- Uorganiske kemikalier
- Koordinationskomplekser
- Deoxycytidin
- Cytidin
- Pyrimidin -nukleosider
- Pyrimidiner
- Kemiteknikker, analytisk
- Spektrumanalyse
- Nukleosider
- Formyltetrahydrofolater
- Tetrahydrofolater
- Folinsyre
- Pterins
- Pteridiner
- Uracil
- Pyrimidinoner
- Coenzymer
- Immunoglobulin -isotyper
- Sulfider
- Anioner
- Ioner
- Elektrolytter
- Hydrogensulfid
- Elektromagnetiske fænomener
- Magnetiske fænomener
- Deoxyribonucleosider
- Elektromagnetisk stråling
- Stråling
- Stråling, ioniserende
- Elementære partikler
- Lys
- Optiske fænomener
- Stråling, ikke -ioniserende
- Deoxyuridin
- Uridin
- Forsinkede handlingsforberedelser
- Capecitabin
- Oxaliplatin
- Bevacizumab
- Irinotecan
- Panitumumab
- Cetuximab
- Fluorouracil
- Leucovorin
- Immunoglobulin G
- Floxuridin
- Magnetisk resonansspektroskopi
- Disulfider
- Røntgenstråler
- Fotoner
- Dehydroftorafur
- (225) AC-DOTA-C (RGDYK)
- 5-Fluoro-2'-deoxyuridin
- Lægemiddelimplantater
Andre undersøgelses-id-numre
Andre undersøgelses-id-numre
- EA2222
- U10CA180820 (U.S. NIH-bevilling/kontrakt)
- EA2222 (Anden identifikator: CTEP)
- NCI-2023-02357 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- EA2222 (Anden identifikator: ECOG-ACRIN Cancer Research Group)
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Studerer et amerikansk FDA-reguleret enhedsprodukt
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