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
- Conditions
- Interventions
- Registration Number
- NCT05863195
- Lead Sponsor
- ECOG-ACRIN Cancer Research Group
- 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 chem...
- Detailed Description
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:
...
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 408
-
Patient must be >= 18 years of age
-
Patient must have confirmed unresectable liver confined metastatic colorectal cancer (CRC).
-
Patient must not have radiographically or clinically evident extrahepatic disease (including but not limited to radiographically positive periportal lymph nodes).
- NOTE: Patients found to have positive periportal nodes at the time of HAI placement can remain on study.
-
Patient may have calcified pulmonary nodules, and/or =< 5 indeterminate and stable (for a minimum of 3 months on chemotherapy) pulmonary nodules each measuring =< 6 mm in maximal axial dimension.
-
Patient's primary tumor may be in place.
-
-
Patient must have received 3-6 months of previous first-line chemotherapy that meet one of the following three criteria: a) have received at least 6 but no more than 12 cycles of first-line cytotoxic chemotherapy (where 1 cycle = 14 days) OR b) have received at least 4 but no more than 8 cycles of first-line cytotoxic chemotherapy (where 1 cycle = 21 days) OR c) have developed new colorectal liver metastases (CRLM) within 12 months of completing adjuvant systemic therapy for stage II-III colorectal cancer.
- NOTE: First-line chemotherapy may have included any of the following regimens as listed in the National Comprehensive Cancer Network (NCCN) Guidelines: leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX) (or equivalent), leucovorin calcium (calcium folinate), 5-fluorouracil, and irinotecan (FOLFIRI) (or equivalent), leucovorin calcium (calcium folinate), 5-fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI), each with or without any of the following: bevacizumab, cetuximab, or panitumumab.
-
Patient must have stable or responding disease on first-line chemotherapy by RECIST 1.1 criteria
-
Patient must meet the following criteria for technical unresectability:
- A margin-negative resection requires resection of three hepatic veins, both portal veins, or the retrohepatic vena cava OR a resection that leaves less than two adequately perfused and drained segments.
- NOTE: Institutional multidisciplinary review is required to confirm unresectability and rule out radiographically positive extrahepatic disease.
-
Patient must undergo CT angiography (chest/abdomen/pelvis) to confirm acceptable hepatic arterial anatomy for HAI and to rule out extrahepatic disease within 4 weeks prior to randomization.
-
Patient must have an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 and be clinically fit to undergo surgery as determined by the pre-operative evaluation.
-
Leukocytes >= 3,000/mcL (obtained =< 14 days prior to protocol randomization)
-
Absolute neutrophil count (ANC) >= 1,500/mcL (obtained =< 14 days prior to protocol randomization)
-
Platelets >= 100,000/mcL (obtained =< 14 days prior to protocol randomization)
-
Total Bilirubin =< 1.5 mg/dL (obtained =< 14 days prior to protocol randomization)
-
Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) =< 3.0 x institutional upper limit of normal (ULN) (obtained =< 14 days prior to protocol randomization)
-
Creatinine =< 1.5 x institutional ULN OR creatinine clearance >= 50 mL/min calculated by the Cockcroft-Gault method (obtained =< 14 days prior to protocol randomization)
-
Calcium >= institutional lower limit of normal (LLN)
-
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
-
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial. Testing for HIV is not required for entry onto the study
-
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A (HAI, floxuridine, standard chemotherapy) Implantation 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. Arm A (HAI, floxuridine, standard chemotherapy) Cetuximab 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. Arm A (HAI, floxuridine, standard chemotherapy) Computed Tomography 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. Arm A (HAI, floxuridine, standard chemotherapy) Intrahepatic Infusion Procedure 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. Arm A (HAI, floxuridine, standard chemotherapy) Panitumumab 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. Arm A (HAI, floxuridine, standard chemotherapy) Single Photon Emission Computed Tomography 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. Arm B (standard chemotherapy) Cetuximab 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. Arm B (standard chemotherapy) Computed Tomography 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. Arm B (standard chemotherapy) Fluorouracil 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. Arm B (standard chemotherapy) Irinotecan 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. Arm A (HAI, floxuridine, standard chemotherapy) Fluorouracil 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. Arm A (HAI, floxuridine, standard chemotherapy) Floxuridine 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. Arm A (HAI, floxuridine, standard chemotherapy) Irinotecan 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. Arm A (HAI, floxuridine, standard chemotherapy) Leucovorin 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. Arm A (HAI, floxuridine, standard chemotherapy) Oxaliplatin 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. Arm B (standard chemotherapy) Leucovorin 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. Arm B (standard chemotherapy) Oxaliplatin 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. Arm B (standard chemotherapy) Bevacizumab 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. Arm B (standard chemotherapy) Panitumumab 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.
- Primary Outcome Measures
Name Time Method Overall survival (OS) 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.
- Secondary Outcome Measures
Name Time Method Incidence of adverse events Up to 5 years Defined according to the Common Terminology Criteria for Adverse Events.
Progression free survival (PFS) 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 O...
Hepatic PFS 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.
Extrahepatic-PFS 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.
Rate of conversion to resectable disease 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.
Intra-operative ineligibility rate 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.
Objective response rate 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) after initiation of treatment (Arm A = surgery, Arm B = cycle 1, day 1 of chemotherapy). Arms will ...
Trial Locations
- Locations (39)
UM Sylvester Comprehensive Cancer Center at Aventura
🇺🇸Aventura, Florida, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
🇺🇸Coral Gables, Florida, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
🇺🇸Deerfield Beach, Florida, United States
UM Sylvester Comprehensive Cancer Center at Hollywood
🇺🇸Hollywood, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
UM Sylvester Comprehensive Cancer Center at Kendall
🇺🇸Miami, Florida, United States
UM Sylvester Comprehensive Cancer Center at Plantation
🇺🇸Plantation, Florida, United States
IU Health North Hospital
🇺🇸Carmel, Indiana, United States
Indiana University/Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States
UCHealth University of Colorado Hospital
🇺🇸Aurora, Colorado, United States
Emory University Hospital/Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Memorial Hospital East
🇺🇸Shiloh, Illinois, United States
University of Kentucky/Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
🇺🇸Grand Rapids, Michigan, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States
Siteman Cancer Center at West County Hospital
🇺🇸Creve Coeur, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center-South County
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center at Christian Hospital
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center at Saint Peters Hospital
🇺🇸Saint Peters, Missouri, United States
Memorial Sloan Kettering Basking Ridge
🇺🇸Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Commack
🇺🇸Commack, New York, United States
Memorial Sloan Kettering Monmouth
🇺🇸Middletown, New Jersey, United States
Memorial Sloan Kettering Bergen
🇺🇸Montvale, New Jersey, United States
Memorial Sloan Kettering Westchester
🇺🇸Harrison, New York, United States
Mount Sinai Hospital
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Nassau
🇺🇸Uniondale, New York, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
West Penn Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Parkland Memorial Hospital
🇺🇸Dallas, Texas, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States